Organophosphorus Chemistry

Organophosphorus Chemistry Volume 12 A Specialist Periodical Report Organophosphorus Chemistry Volume I 2 A Review ...

Author: D. W. Hutchinson | J. A. Miller

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Organophosphorus Chemistry Volume 12

A Specialist Periodical Report

Organophosphorus Chemistry Volume I 2

A Review of the Literature published between J u l y 1979 and J u n e 1980

Senior Reporters

D. W. Hutchinson Department of Chemistry and Molecular Sciences, University of Warwick J. A. Miller Chemistry Department, University of Dundee Reporters

D. W. Allen Sheffield City Polytechnic R . S. Edmundson University of Bradford J. B. Hobbs The City University, London J. F. Marecek State University of N e w York at Stony Brook, USA

F. Ramirez State University of N e w York at Stony Brook, USA

J. C. Tebby North Staffordshire College of Technology, Stoke-on- Trent

S. Trippett University of 1eicester B. J. Walker Queen's University of Belfast

The Royal Society of Chemistry Burlington House, London W1 V OB N

British Library Cataloguing in Publication Data Organophosphorus chemistry.-Vol. 12.(A Specialist periodical report) 1. Organophosphorus compounds - Periodicals I. Royal Society of Chemistry 547’.07’05 QD412.Pl

ISBN 0-85186-106-7 ISSN 0306-07I 3

Copyright 0 1981 The Royal Society of Chemistry

All Rights Reserved No part of this book may be reproduced or transmitted in any form or by any means - graphic, electronic, including photocopying, recording, taping, or information storage and retrieval systems - without written permission from The Royal Society of Chemistry Printed in Great Britain by Adlard and Son Ltd Bartholomew Press, Dorking

Introduction

The present Senior Reporters would like to acknowledge the efforts of Professor Stuart Trippett in founding this Series and maintaining its international reputation over the past eleven years. In this volume we introduce the first of a series of occasional reviews written by specialists in particular areas of Organophosphorus Chemistry. The occasional review this year is ‘Phosphoryl Transfer from Phosphomonoesters and Adenosine 5’-Triphosphate’, by Professor F. Ramirez and Dr J. F. Marecek of the State University of New York at Stony Brook, and we hope to continue these occasional reviews in subsequent volumes. The format of the rest of the Report is similar to that of previous years except that the chapter on phosphazenes has temporarily been discontinued. During the past year, spectacular progress has continued to be made on the stereospecificity of enzymic reactions using compounds which contain phosphate or thiophosphate groups. There has been a renewed interest in enzyme mechanisms in general, and a large number of phosphorylated proteins have been identified and examined as possible intermediates in enzymic reactions. The methodology of the phosphotriester approach to the synthesis of oligonucleotides has been refined, including the improvement of solid-phase methods which could be of considerable use for the synthesis of oligodeoxyribonucleotides for genetic engineering. Cyclophosphamide has continued to attract attention, and an occasional review in next year’s Report will be devoted to this important therapeutic agent. Other areas of interest in the past year include the use of chiral phosphine ligands in reductions, low-temperature e.s.r. studies of phosphoranyl radicals in which trigonal-bipyramidal equilibria have been frozen out, the use of arylthiophosphine sulphide dimer in the halogenation of unsaturated phosphoric esters, and the investigation of the acidities of hydroxyphosphoranes. D. W. H. J. A. M.

10 June 1981

V

Contents Chapter 1 Phosphines and Phosphonium Salts

1

By D. W. Allen

1 Phosphines

1

Preparation From Halogenophosphines and Organometallic Reagents From Metallated Phosphines By Addition of P --H to Unsaturated Compounds By Reduction Miscellaneous Methods React ions N iicleoph i 1ic Attack at Carbon Nucleoph i l ic At tack at Halogen Nucleophilic Attack at Other Atoms Miscellaneous 2 Phosphonium Salts

3 7

8 9 12 12 14 16 19 22

Preparation Reactions Alkaline Hydrolysis Additions to Unsaturated Phosphonium Salts Miscellaneous 3 Phospholes and Phosphorins

Chapter 2 Quinquecovalent Phosphorus Compounds By

1 1

22 24 24 26 27 29

32

S. Trippett

1 Introduction

32

2 Structure and Bonding

32

3 Hydroxyphosphoranes

34

4 PH-Phosphoranes

35

5 Acyclic Phosphoranes

37

6 Four-membered Phosphoranes

38

7 Five-membered Phosphoranes

38

8 Six-membered Phosphoranes

42

9 Six-co-ordinate Species

42

vii

...

Vlll

Contents

Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller 1 Introduction 2 Halogenophosphines Preparation Physical and Structural Properties Reactions with Alkenes or Alkynes Reactions with Amines and Derivatives Reactions with Carbonyl Compounds Reactions with Acetals and Alcohols Reactions with Phosphorus(Ir1) Compounds Miscellaneous Reactions 3 Silylphosphines 4 Halogenophosphoranes Preparation Physical and Structural Aspects Reactions Reactions that are Relevant to Organic Synthesis

45

Chapter 4 Phosphine Oxides and Related Compounds By J. A. Miller 1 Introduction 2 Preparation of Simple Oxides 3 Preparations and Reactions Related to Alkene Synthesis 4 Reactions and Properties involving the P=O Group 5 Reactions of the Side-chain 6 Chemistry of Cyclic Phosphine Oxides 7 Miscellaneous Structural and Physical Aspects

63

Chapter 5 Tervalent Phosphorus Acids By B. J. Walker 1 Phosphorous Acid and its Derivatives Nucleophilic Reactions Attack on Saturated Carbon Attack on Unsaturated Carbon Attack on Nitrogen Attack on Oxygen Attack on Halogen Electrophilic Reactions Cyclic Esters of Phosphorous Acid Miscellaneous Reactions 2 Phosphonous and Phosphinous Acids and their Derivatives

76

45

45 45

46 47 48

50 52 53 55

56 58

58 59 60 62

63 63 65 67 70 71 74

76 76 76 77 82 82 85 88

90 91

93

ix

Contents

Chapter 6 Quinquevalent Phosphorus Acids

96

B y R. S. Edmundson 1 Synthetic Methods

General Phosphoric Acid and its Derivatives Phosphonic and Phosphinic Acids and their Derivatives 2 Reactions

General Phosphoric Acid and its Derivatives Phosphonic and Phosphinic Acids and their Derivatives

Chapter 7 Phosphates and Phosphonates of Biochemical Interest By D. W. Hutchinson

96 96 97 100

109 109 111 120

127

1 lntroduction

127

2 Coenzymes and Cofactors

128

Nicotinamide Coenzymes Phosphoenolpyruvate Py rid oxal Phosphate 0t her Coenzymes

128 129 130 130

3 Sugar Derivatives

130

4 Phospholipids

131

5 Phosphonates

133

6 Enzymology

136

Enzyme Mechanisnis Phosphoproteins

7 Other Compounds of Biochemical Interest Chapter 8 Phosphoryl Transfer from Phosphornonoesters and Adenosine 5’-Triphosphate

136 138 139

142

B y F. Ramirez and J. F. Marecek 1 Types of Phosphoryl Transfer

142

2 Phosphoryl Transfer from Aryl Dihydrogen Phosphates

146

3 Does PO,- Add to Non-enolized Ketones in Solution?

153

4 Mechanims of Non-enzymatic Phosphoryl Transfer from ATP

154

5 Enzymatic Hydrolysis of ATP : Actomyosin MgATPase

in Muscle Contraction 1*

159

Contents

X

Chapter 9 Nucleotides and Nucleic Acids B y J . 6. Hobbs

164

1 Introduction

1 64

2 Mononucleotides

164

Chemical Synthesis Cyclic Nucleotides Affinity Chromatography

173 177

3 Nucleoside Polyphosphates

178

Chemical Synthesis Affinity Labelling

4 Oligo- and Poly-nucleotides Chemical Synthesis Enzymatic Synthesis Sequencing Other Studies

5 Analytical Techniques and Physical Methods

Chapter 10 Ylides and Related Compounds

164

178 188 190

190 198 200 202 203

206

By 8. J. Walker 1 Methylenephosphoranes Preparation and Structure Reactions Aldehydes Ketones Miscellaneous

206 206 209 209

2 Reactions of Phosphonate Anions

225

3 Selected Applications in Synthesis

233

Pheromones Prostaglandins Carbohydrates Carotenoids Non-benzenoid Aromatic Compounds Miscellaneous

Chapter 11 Physical Methods By J. C. Tebby 1 Nuclear Magnetic Resonance Spectroscopy Biological and Analytical Applications

216

219

233 234 235 236 236 237

240 240 240

xi Chemical Shifts and Shielding Effects Phosphorus-3 1 (71. of PI1 compounds O p of and PI\- co111pollilds O p of PV and P\-1 compounds Carbon- 1 3 Hydrogen- I Eq u i I i bri a, S11 i f t Reagents, and 1- i q ~ii d C rj.st a1s Variable- t c'm pera t 11re Studies Pseudorotat ion and Restricted Rotation Other Studies Configuration Spi ti-S pi n Coil pli ng JIJP and JpIr J I * Iand ? JPN JIY* J1)rr

JIY*,,IT

Relaxation and N.Q.R. Studics

240 240 240 240 24 1 242 243 242 243 243 244 244 244 245 245 245 246 246 247

2 Electron Spin Resonance Spectroscopy

248

3 Vibrational and Rotational Spectroscopy

250

Band Assignments Stereochemistry Bonding Microwave Spectra

4 Electronic Spectroscopy Absorption Photoelectron

5 Diffraction X-Ray Electron and Neutron 6 Dipole Moments, Kerr Effect, and Polarography Dipole Moments and Kerr EfTect Polarographic Studies 7 Mass Spectrometry 8 pK,, Thermochemical, and Kinetic Studies 9 Chromatography G.1.c. T.1.c. H.p.1.c. Column and Gel Chromatography Author Index

250 25 1 25 1 252 252 252 253 254 254 256 257 257 257 258 258 260 260 261 26 1 26 1

262

Abbreviations" AIBN Boc CIDNP CNDO DAD DBN DBU d.c. DCC DEAE DMF DMSO ENU FID g.c.-m.s. g.1.c. HMPT h.p.1.c. INDO LCAO MIND0 MNU PEI PTFE TDAP TFAA THF t.1.c. TPS-C1 TsOH

bisazoisobutyronitrile but yloxycarbony1 chemically induced dynamic nuclear polarization complete neglect of differential overlap diethyl azodicarboxylate 1,5-diazabicyclo[4.3.O]non-5-ene

1,5-diazabicyclo[5.4.O]undec-5-ene direct current dicyclohexylcarbodi-imide diethylaminoethyl dimethylformamide dimethyl sulphoxide N-et hy I-N-nitrosourea free induction decay gas chromatography-mass spectrometry gas-liquid chromatography hexamet hy 1phosphort riam ide high-performance liquid chromatography intermediate neglect of differential overlap linear combination of atomic orbitals modified intermediate neglect of differential overlap N-methyl-N-nitrosourea polyethyleneimine poiytetrafluoroethylene tris(dimethy1amino)phosphine trifluoroacetic acid tetrahydro furan thin-layer chromatography tri-isopropylbenzenesulphonyl chloride toluene-p-sulphonic acid

*Abbreviations used in chapters 7-9 1 and Biochern. J., 1970,120,449.

are detailed in Biochern. J., 1978, 171,

I

Phosphines and Phosphonium Salts BY

D. W. ALLEN

1 Phosphines Preparation.-From Halogenophosphines and Organometallic Reagents. The Grignard procedure has been used to prepare a range of long-chain (Cl0--Cl9) trialkylphosphines,l the p-alkyl-substituted phenylphosphines (1),2 the substituted vinylphosphines (2) and (3),3 and a sample of triethylphosphine that is radio-labelled at both phosphorus and the P-~arbon.~ A mixture of exo- and endo-isomers of the phosphine (4) results from addition of methylmagnesium bromide to a corresponding mixture of isomers of 2-norbornyldichlorophosphine. Surprisingly, the usual mode of addition of the halogenophosphine to the Grignard reagent gives a negligible yield of the ph~sphines.~ A convenient Grignard procedure has been describeds for the synthesis of the 1,2-bisphosphinoethanes ( 5 ) from the corresponding bis(dichlorophosphino)ethane, prepared by a modification of the original procedure given in a 1975 patent.? Many examples of the use of organolithium reagents in phosphine synthesis have been reported in the past year. Procedures for the synthesis of the three

k(=J+-

(1)

PPh 3 -n

R = Pr,Bu, hexyl, or octyl n = 1-3

Ph,PC(R)=CR, (2) R = H or Me

R,PCH,CH,PR,

&PMe2 (4)

3 4 5 8

7

PhP(CH=CHMe), (3 1

(5) R = Me, Et, or C,H,,

S. Franks, F. R. Hartley, and D . J. A. McCaffrey, J. Chem. SOC.,Perkin Trans. 1, 1979, 3029 S. 0. Grim, D. P. Shah, C. K. Haas, J. M. Ressner, and P. H. Smith, Inorg. Chim. Acta, 1979, 36, 139. S. 0. Grim, R. P. Molenda, and J. D. Mitchell, J . Org. Chem., 1980, 45, 250. M. Kanska and S. Drabarek, Radiochem. Radioanal. Lett., 1979, 39, 233. L. D. Quin, M. J. Gallagher, G. T. Cunkle, and D. B. Chesnut, J. Am. Chem. SOC.,1980, 102, 3136. R. J. Burt, J. Chatt, W. Hussain, and G. J. Leigh, J. Organornet. Chem., 1979, 182, 203. A. D. F. Toy and E. H. Uhing, US P. 3 976 690.

1

2

Orgunophosphorus Chemistry

isomeric tris(trifluoromethylpheny1)phosphines and a range of (perfluoroary1)phosphines bearing perfluoroalkyl ether substituents in the aryl rings have been d e s ~ r i b e dA . ~ modified preparation of tri-( 2-pyridy1)phosphine viu the metallation of 2-bromopyridine with butyl-lithium has been developed. Attempts to prepare the corresponding 3-pyridyl- and 4-pyridyl-phosphines from the related bromo-pyridines failed to give clean products. l o A range of aw-bis(dipheny1phosphino)aryl ethers, e.g. ( 6 ) , has been prepared via the reaction of chlorodiphenylphosphine with the appropriate crw-dilithio-derivatives." Shaw's group have described the synthesis of further chelating diphosphines, e . g . (7), that bear bulky groups at phosphorus and in which the phosphorus atoms are separated by a long alkyl chain.12,l 3 Allyl(t-butyl)amine undergoes metallation at the terminal carbon of the ally1 group, and the reaction of the resulting organolithium reagent with phenyldichlorophosphine gives the heterocycle (8).l 4 The reaction of phenyldichlorophosphine with 1, 1'-dilithioferrocene yields the phosphino-[l Iferrocenophane (9), which on treatment with organolithium reagents undergoes ring-opening to form the lithium reagent (10); this has been used for the synthesis of mixed phosphino-arsino-ferrocenes. l5 Interest in the synthesis of chiral phosphines continues, and various methods for the synthesis of such compounds have been reviewed, together with procedures for the synthesis of tertiary phosphines bearing either an o-anisyl or o-dimethylaminophenyl group, involving ortho-metallation of anisole or of N N dimethylaniline followed by reaction with halogenophosphines. Full details of the preparation of two chiral forms of the phosphinoamine ( l l ) , from the reaction of the ortho-lithiated (aminoalky1)ferrocene with chlorodiphenylphosphine, have now appeared." The use of phosphinites derived from the optically active alkaloid cinchonine in the synthesis of chiral phosphines continues to develop. The diastereoisomeric phosphinites ( 12) can be separated by crystallization of the related copper(1) cyanide complexes. The reaction of the purified diastereoisomers (freed from copper by treatment with cyanide) with an organolithium reagent then gives the chiral phosphines (1 3) in very high optical purity.'* In related work, it has been shown that consecutive substitution of chlorine in phenyldichlorophosphine with lithium cinchoninate followed by arylcyanocuprate reagents leads selectively to the corresponding (R)-phosphinite esters, which are then converted into the chiral phosphines as described above, by H K. C . Eapen and C . Tamborski, J . Fluorine Chcni., 1980, 15, 239. 'J H . Gopal, C. E. Snyder, and C . Tamborski, J . Fluorine Chent., 1979, 14, 511. 10 K . Kurtev, D. Ribola, R . A . Jones, D . J . Cole-Hamilton, and G . Wilkinson, J . Chenr. Soc.,

Dalion Trans., 1980, 55. M . Tashiro, T. Sumida, and G . Fukata, J . Org. Cheni., 1980, 45, 1156. N . A. Al-Salem, W. S. McDonald, R. Markham, M. C . Norton, and B. L. Shaw, J . Chrm. Soc'., Dalton Trans., 1980, 59. 13 N . A. Al-Salem, H . D . Empsall, R . Markham, B. L. Shaw, and B. Weeks, J . Chern. Soc., Dalton Trans., 1979, 1972. 14 D. Haenssgen and E. Odenhausen, Chent. Ber., 1979, 112, 2389. 15 D . Seyferth and H. P. Withers, Jr., J . Organomct. ('hem., 1980, 185, C l . 16 L. Horner, Pure Appl. Chem., 1980, 52, 843. 1: W. R. Cullen, F. W. B. Einstein, C.-H. Huang, A. C. Willis, and E-Shan Yeh, J . Ant. Chctn. Soc., 1980, 102, 988. in W. Chodkiewicz, D. Jore, A . Pierrat, and W. Wodzki, J . Organornet. ChPm., 1979, 174, c21. 11

12

3

Phosphines and Phosphonium Salts

(6)n = 1 or 2

(7)

q Fe

PhLi

@2

PPh

Fe

treatment with an organolithium reagent.lg Similar studies of the reactions of organolithium reagents with diastereoisomeric phosphinites derived from menthol have also been reported.20?21 Treatment of acetate esters with lithium bis(trimethylsily1)amide and diorganohalogenophosphines affords a synthesis of the functionalized phosphines (14). 22 The reaction of phosphorus trichloride with (cyanomethy1)tributylstannane gives a much improved route to the (cyanomethy1)phosphine (15), described as an air-stable, crystalline solid, of low nucleophilic reactivity. 23 Preparation from Metallated Phosphines. The past year has seen a considerable number of applications of metallo-phosphide reagents in the synthesis of a wide range of new phosphines, many of which are of interest as chiral ligands in transition-metal complexes that are used as catalysts for asymmetric hydrogenation and other reactions.

R',PCH2C02R2 (14) R' = Ph, E t 0 , o r Me2N

3Bu,SnCH,CN + PC1,

--+

P(CH,CN),

R 2 = Me or Et

19 20 21

22 23

W. Chodkiewicz and D. Guillerm, Tetrahedron Lett., 1979, 3573. J . Omelanczuk, W. Perlikowska, and M. Mikolajczyk, J . Chem. SOC.,Chem. Commun., 1980, 24. M. Mikoiajczyk, J. Omelanczuk, and W. Perlikowska, Tetrahedron, 1979, 35, 1531. 1. A. Stepanov, A. Yu. Platonov, and V. N. Chistokletov, Zh. Obshch. Khim., 1979, 49, 2389 (Chem. Abstr., 1980, 92, 129 019). 0. Dahl and S. Larsen, J. Chem. Res., 1979, ( S ) , 396; ( M ) , 4645.

4

Organophosphorus Chemistry

The reactions with alkyl halides of lithio-phosphide reagents, obtained by cleavage of phenyl groups from alkyldiphenylphosphines by using lithium in THF, have been used to prepare a range of chiral, unidentate phosphines of the type PhPR1R2 (R'=Me, Et, or Pr; R 2 = E t , Pr, or C,H,,). The same paper reports the reaction of lithium cyclohexyl(phenyl)phosphide with the dimesylate of 1,4-butanediol, giving the chiral chelating diphosphine (1 6). 24 The reactions of lithium diphenylphosphide with alkyl halides have been used in the synthesis of acu-bis(diphenylphosphino)alkanes, e.g. (1 7),25v26 and with a polymer-bound tosylate to give the polystyrene-bonded (long-chain alky1)diphenylphosphine ( 1 8 y 7 Treatment of the readily accessible spirohydrocarbon (19) with lithium diphenylphosphide gives the isomeric phosphines (20).28 In related work, (1ithiomethyl)diphenylphosphine has been used in the synthesis of the (phosphinoalky1)cyclopentadienide ligand (21), from which a series of (phosphinoalky1)metallocenes and related macrocyclic complexes may be prepared.2 9

Sodium diphenylphosphide reacts with the mesylate of (S)-s-butyl alcohol to give (R)-s-butyldiphenylph~sphine,~~ and with the tosylate (22) it gives, unexpectedly, the phosphine (23), in which the carbon skeleton has been rearranged.31 This reagent also causes the cleavage of the aryl-oxygen bond in coumaran, giving a route to the phenolic phosphine (24).32 Potassium diphenylphosphide has been used in the synthesis of the chiral ( &aminoalkyl)phosphine (25), derived from ephedrine.33 The reaction of lithium dimethylphosphide (conveniently obtained by cleavage of dimethylphenylphosphine by lithium, in THF) with o-dichlorobenzene gives N.C. Payne and D. W. Stephan,

Can. J . Chc.m., 1980, 58, 15. P. W. Clark, O r g . Prcp. ProccJil. lnt., 1979, 11, 103. 2 f i W. E. Hill, C. A . McAuliffe, I . E. Niven, and R . V. Parish, Inorg. Chim. Actu, 1980,38, 273. 27 J . M. Brown and H . Molinari, Tetrahedron Lett., 1979, 2933. 2 8 T . Kauffniann, J. Ennen, H . Lhotak, A . Rensing, F. Steinseifer, and A . Woltermann, Angew. Chem., Int. Ed. Engl., 1980, 19, 328. 2:' N.E. Schore, J . Am. Chem. Soc., 1979, 101, 7410. 3" A . Raffaelli, R . Lazzaroni, and P. Salvadori, Chim. Intl. (Milan), 1979, 61, 427. 3 1 Y . Nakamura, S. Saito, and Y . Morita, Chrm. Lrtt., 1980, 7 :32 N.A . Bondarenko, E. N. Tsvetkov, E. I . Matrosov, and M . I . Kabachnik, Bull. Acad. S i. USSR, Diu. Chenr. Sci., 1979, 28, 399. :m W. Beck and U . Nagel, Z. Anorg. Allg. Chem., 1979, 458, 22.

2.1 2;)


5

Me

I

H-C-NHMe H-C-

I

I Ph

PPh (26)

(27)

a route to the otherwise difficultly accessible diphosphine (26; X = PMe,). Similar reactions with a range of o-bromophenylalkyl ethers, amines, arsines, and stibines yield the chelating ligands (26; X=OMe, SMe, NMe,, AsMe,, or SbMe,).34 In related work, the reaction of sodium methylphenylphosphide (obtained from the cleavage of methyldiphenylphosphine with sodium in liquid ammonia) with o-dichlorobenzene yields a mixture of the diastereoisomeric forms of the diphosphine (27), which have been resolved via a new large-scale procedure involving palladium complexes of optically active a m i n e ~ . ~ ~ The reactions of lithio-phosphides derived from bis-secondary phosphines with alkyl halides have been employed in the synthesis of a range of macrocyclic phosphines, e.g. (28)3s and (29).37A similar procedure, using a related lithioarsenide, has given the phosphino-arsino-macrocycle (30).3*

(29) X = 0, S, NPh, NMe, PPh, or CH,

:I'

36 37

38

(30)

W. Levason, K. G. Smith, C. A . McAuliffe, F. P. McCullough, R . D. Sedgwick, and S. G . Murray, J . Chem. Soc., Dalton Trans., 1979, 1718. N . K. Roberts and S. B. Wild, J . Am. Chem. SOC.,1979, 101, 6254. M. Ciampolini, P. Dapporto, N . Nardi, and F. Zanobini, J . Chem. Soc., Chem. Commun., 1980, 177.

E. P. Kyba, A . M . John, S. B. Brown, C . W . Hudson, M . J . McPhaul, A . Harding, K. Larsen, S. Niedzwiecki, and R . E. Davis, J. Am. Chem. SOC., 1980, 102, 139. E. P. Kyba and S . 4 . P. Chou, J . Chem. SOC.,Chem. Commun., 1980, 449.

6

Organophosphorus Chemis!r-I,

The reactions of metallo-phosphides with tosylates have been widely employed in the synthesis of chiral, chelating d i p h o ~ p h i n e s . ~I n~ -some ~ ~ cases, naturally occurring chiral substances have been used as the starting material, thereby eliminating the need for optical resolution at some stage. Thus (31):j9 is derived from tartaric acid, and (32)40and (33)41are derived fromcarbohydrates. Amongst other new systems prepared are (34),42( 35L4:j and (36).44Polymer-bound chiral diphosphines have also been prepared.47 Ph ,P PPh

Me

PPh

Me

PPh ,

Ph *P (31)

(32)

(33)

( 3 6 ) n = 1-4

Chiral unidentate phosphines have also been prepared by the tosylate route from mannitol, xylose, and glucose.48 Metallo-phosphide reagents have also been used in a new route to (/?-hydroxyethyl)phosphine~,~~ in the synthesis of a range of multidentate p h o s p h i n e ~ , ~ ~ - ~ ~ including the hitherto unknown methylidynetrisphosphine (Me,P),CH,S1 and in the preparation of a number of new PP-diphosphines bearing bulky alkyl groups.56 Primary phosphines co-ordinated to transition metals also undergo

J1

J. Kottner a n d G . Greber, Chcm. Ber., 1980, 113, 2323. T. H. Johnson a n d C i . Rangarajan, J . Org. ChcJni.,1980, 45, 62. H . B. Kagan, J . C. Fiaud. C . Hoornaert, D. Meyer, and J . C. Poulin, Bull. Sac. C'him.Bclg.,

J2

T. H . Johnson, D. K . Pretzer, S. Thomen, V. J . K . C h a f i n , a n d G . Rangarajan. J . Org.

39 4o

1979, 88, 923.

43

44 45 46 47

4# 49 50

61

Ciicim., 1979, 44, 1878. W. A. Henderson. Jr.. US P. 4 166 824.

P. Aviron-Violet, Y. Colleuille, a n d J . Varagnat, J. Mol. Catal., 1979, 5 , 41. J. M. Brown a n d B. A. Murrer, Tetrahedron Lett,, 1980, 21, 581. T. Hayashi, M . T a n a k a , Y. Ikeda, a n d I. Ogata, Bull. Chem. Soc. Jpn., 1979, 52. 2605. S. J . Fritschel, J . J . H. Ackerman, T. Keyser, a n d J. K . Stille, J . Org. Chem., 1979,44, 3152. H. Brunner and W. Pieronczyk, J . Chenr. Rcs., 1980, ( S ) , 74; ( M ) ,1251. A. Tzschach, W. Radke, a n d W. Uhlig, Z. C h ~ m .1979, , 19, 252. E. A r p a c a n d L. Dahlenburg, Z. Naturforsch., Teil.B, 1980, 35, 146. H. H. Karsch, U. Schubert, a n d D. Neugebauer, Angew. Ch~rn.,Int. Ed. Engl., 1979, 18, 484.

52

53 54

55

H . H . Karsch, B. Zininier-Gasse, D . Neugebauer, a n d U . Schubert, Angew. Chem.. I n / . Ed. Engl., 1979, 18, 484. H . H. Karsch, Z. Naturfiwsch., Teil. B , 1979, 34, 1171. H. H . Karsch. Z. Naturforsch.. Teil.B, 1979, 34, 1178. A. A. M . Ali, G. Bocelli, R. K . Harris, a n d M. Fild, J . Chem. Soc., Dalton Trans., 1980, 638.

Phosphirres arid Phosphonium Salts

7

metallation, and the resulting co-ordinated metallo-phosphide may be alkylated 56 or treated with halogenophosphines to form co-ordinated PH-functional di-, tri-, and tetra-pho~phines.~' The reactions of lithium bis(trimethylsi1yl)phosphide with dichlorophosphines give a series of silylated triphosphines; on heating, these are converted into cyclic polyphosphorus Baudler's group has continued to apply dimetallated phosphide reagents in the synthesis of both homocyclic and heterocyclic phosphines. Among new systems reported in the past year are the threemembered-ring P,Si and As,P heterocycle^.^^--"^ The synthesis and properties of three-membered-ring phosphines have been reviewed.66 Prc.purution by Addition of' P--H ro Unsuturured Compounds. This method continues to be used extensively for the preparation of multidentate phosphine ligands, which may also involve other donor atoms. A key step in the synthesis of the tetraphosphine (37) is the radical-catalysed addition of 1,3-bis(phenyIphosphino)propane to ally1 Photochemically induced addition of diphenylphosphine to unsaturated silanes has been employed in the synthesis of the phosphines (38)68and (39).69The latter, o n treatment with cyclopentadienyllithium, followed by butyl-lithium, is converted into a ligand similar to (21), bearing both phosphine and cyclopentadienide-anion donor sites. Aminopolyphosphine ligands, e.g. (401, prepared by the photochemical addition of 2-cyanoethylphosphine to two equivalents of vinyldiphenylphosphine followed by reduction of the cyano-group, have been anchored to a controlled-pore glass support, and subsequently converted into a transition-metal catalyst Meek's group has also described the synthesis of a variety of new multidentate ligands, e.g. (41), by a combination of addition of P---H to unsaturated systems with other well-established synthetic routes in phosphorus chemistry.71Addition reactions of diphenylphosphine to vinyldiphenylphosphine that is co-ordinated to a transition metal, and of co-ordinated diphenylphosphine to vinyldiphenylphosphine, have also been reported.72Full details have now appeared of the addition of secondary phosphines to alkynyldiphenylphosphines that are coordinated to platinum or palladium.73 CJ'~

97

M. Baacke, S. Morton, 0. Stelzer, and W. S. Sheldrick, Chrm. Ber., 1980, 113, 1343. M. Baacke, S. Morton, G . Johannsen, N. Weferling, and 0. Stelzer, Chem. Bcr., 1980, 113,

1328.

:A 59

60

W. Holderich and G . Fritz, Z.Anarg. AIIg. Chc,tn., 1979, 457, 127. M. Baudler and E. Tolls, Z . Chcm., 1979, 19, 418. M. Baudler, E. Tolls, E. Clef, D. Koch, and B. Kloth, Z . Anorg. Allg. Chem., 1979. 456, 5.

M . Baudler and G . Reuschenbach, Z. Anorg. Allg. C h ~ m .1980, , 464,9. M . Baudler, G . Reuschenbach, D. Koch, and B. Carlsohn, Chem. Ber., 1980, 113, 1264. M. Baudler, W. Driehsen, and S. Klautke, Z . Anorg. AIIg. C h ~ m . 1979, , 459, 48. M. Baudler and H. Jongebloed, Z . Anorg. Allg. Chem., 1979, 458, 9. '15 M. Baudler and D. Habermann, Angew. Chem., Inr. Ed. Engl., 1979, 18, 877. M. Baudler, Pure Appl. Cheni., 1980, 52, 755. 67 M. Baacke, 0. Stelzer, and V. Wray, Chem. Ber., 1980, 113, 1356. 6 8 2. C. Brzezinska and W. R. Cullen, Inorg. Chem., 1979, 18, 3132. (i'J N . E. Schore and S. Sundar, J . Organomet. Chem., 1980, 184, C44. 7 " K . J . Uriarte and D. W. Meek, Inorg. Chim. Acta, 1980, 44, L283. 7 1 K . Uriarte, T. J . Mazanec, K. D. Tau, and D. W. Meek, fnorg. Chem., 1980, 19, 79. 7" K . L. Keiter, Y. Y . Sun, J . W. Brodack, and L. W. Carey, J . A m. Chem. Soc., 1979, 101,

61 6,

;:I

2638. A . J . Carty, D . K. Johnson, and S. E. Jacobson, J . A m . ChPm. Soc., 1979, 101, 5612.

8

Organophosphorus Chemistry PhPH(CH,) ,P(Ph)(CH,) ,P(Ph)(CH,),PHPh

R' R2,Si(CH,),PPh,

(37)

(38) R' = Me or C1 R 2= Me, C1, or OSiMe, n = 2-8

Ph,PCH,CH,Si(Cl)Me,

(39) H,N (CH ,1 ,P[ (CH ,) ,PPh, 1

Ph,P(CH,) ,P(Ph)CH,CH ,CH *R

(40)

(41) R = NMe, or OPh

Examples of base-catalysed addition reactions have also been reported. Addition of the bis-primary phosphine (42) to diphenylvinylarsine yields the new ligand (43).74 Base-catalysed addition of neomenthylphenylphosphine [obtainable from the naturally occurring, inexpensive ( - )-menthol] to diphenylvinylphosphine gives the diphosphine (44), which can be separated (by fractional crystallization) into pure diastereoisomers that differ only in the configuration of the chiral phosphorus atom; this is the first example of a self-resolving chiral ditertiary phosphine. The related compounds (45) and (46) have also been obtained as mixtures of diastereoisomers, by the addition of neomenthylphenylphosphine to phenyldivinylphosphine and dimethylvinylphosphine sulphide, respectively. Preparation by Reduction. Reduction of phosphine oxides with trichlorosilane has been used in the synthesis of unsaturated heterocyclic phosphines, e.g. (47), 76-78 and of the chiral phosphines (48)79 and (49).80The latter is one of the

1

KOBU' Ph,AsCH=CH,

[Ph,As(CH,),],PCH,

,, 0 \

CH,P[(CH,),AsPh,

1,

(43)

Ph

(CH 1 ,PPh

H&Me Me' Me 74 75 76

77

78

79 80

PhP[ (CH,),P(neoMen)Ph],

(neoMen)(Ph)P(CH,),P(S)Me,

(45)

(46)

(44)

M. M. Taqui Khan, R . Mohiuddin, and M. Ahmed,J. Coord. Chem., 1980, 10, 1. R. B. King, J . Bakos, C. D. Hoff, and L. Marko, J . Org. Chem., 1979, 44, 3095. Y . Segall, E. Shirin, and I. Granoth, Phosphorus Sulfur, 1980, 8, 243. K. A. Petrov, V. A. Chauzov, L. P. Chernobrovkina, and Yu. N. Lebedeva, Zh. Obshch. Khini., 1979, 49, 2622 (Chem. Abstr., 1980, 92, 94 516). L. D. Quin and E. D. Middlemas, Pure Appl. Chem., 1980, 52, 1013. M. Kumada, K. Tamao, H . Yamamoto, H. Matsumoto, N. Miyake, and T. Hayashi, Jpn. Kokai Tokkyo Koho 79 39 059 (Chem.Abstr., 1979,91,91 764). H. Brunner and W. Pieronczyk, Angew. Chem., Int. Ed. Engl., 1979, 18, 620.


9

most easily prepared optically active chelating diphosphines, and it gives one of the highest optical yields reported for asymmetric hydrogenation reactions that are catalysed by phosphine-rhodium([) complexes. Phosphine oxides with at least one phosphorus-aryl bond are reduced to the phosphine by equimolar amounts of magnesium and dicyclopentadienyltitanium dichloride in boiling THF. The titanium reagent is an inoffensive solid which can be handled in air, and is commercially available. Although easier to use than the silane reagents, its action would appear to be less general.s1 Reduction of phosphonates using lithium aluminium hydride has been employed in the synthesis of the methylenediphosphines (50).82A wide range of phosphine dihalides has been reduced to the tertiary phosphines, using hydrogen under pressure, in pyridine as Mathey has reported further applications of the nickelocene-ally1 iodide reagent for the reduction of phosphine sulphides. It has now been shown that this reagent selectively reduces P=S in the presence of P-0 bonds** or other sensitive, reducible, functional groups, and studies with chiral compounds show that the reductions proceed with full retention of configuration at p h o s p h ~ r u s86. ~ ~ ~ The new chiral diphosphine (51) has been obtained by reduction, by sodium, of the corresponding disulphide, which is conveniently accessible by Diels-Alder addition of trans-vinylenebisdiphenylphosphinesulphide to the chiral, naturally occurring diene ( - )-~t-phellandrene.~'

Miscellaneous Methods. A synthetic route to the phosphorus analogue (52) of the alkaloid carnegine has been developed with the aid of a computer program.** A number of applications of (hydroxymethy1)phosphines in the synthesis of

Ph

PPh

Ph zPy'l--pphz PhP(R)CH ,PH , (50) R = Ph or H (51)

F. Mathey and R . Maillet, Tetrahedron Lett., 1980, 21, 2525. H. Weichmann, B. Ochsler, I . Duchek, and A . Tzschach, J . Organomet. Chem., 1979, 182,

465. s3 M. Masaki and N. Kakeya, Jpn. Kokai Tokkyo Koho 79 84 528 (Chem. Abstr., 1979,91, 193 418). 84 F. Mathey and F. Mercier, J . Chem. Soc., Chem. Commun., 1980, 191. 85 F. Mathey and F. Mercier, J. Organomet. Chem., 1979, 177, 255. 86 F. Mathey and F. Mercier, Tetrahedron Lett., 1979, 3081. 87 M. Lauer, 0. Samuel, and H. B. Kagan, J. Organomet. Chem., 1979, 177, 309. 8 8 C. Laurenco and G. Kaufmann, Tetrahedron Lett., 1980, 21, 2243.

10


heterocyclic systems, e.g. (53)s9 and (54),90 have been r e p ~ r t e d . * Complete ~-~~ silylation of tris(hydroxymethy1)phosphine gives the (trialkylsiloxymethy1)phosphines (55),93 and tris- and bis-(hydroxymethy1)phosphines react with optically active secondary amines to give optically active (aminomethy1)phosphines, e.g. (56).gq (Aminomethyl)phosphines have also been prepared from the reactions of secondary phosphines with d i a m i n ~ m e t h a n e s The . ~ ~ synthesis of the chiral (&aminoethyl)phosphines (57) from optically active amino-acids has been reported.96

MeoqpM rN7 IPR' R'

RIP

Me0 \

Me

(52)

LN

R2 (53) R' = Ph or alkyl

R 2 =aryl

(R,SiWH,) P

P[ CH ,N(R)CH(Me)Ph]

(55) R = Me or Et

(56) R = Me or Et

(54) R' = Ph or alkyl R 2 = Me or Et

RCH(NMe,)CH,PPh,

(57) R

=

Me, CH,Ph, Pr', B u t , or Ph

Japanese workers have continued to develop the range of chiral N-acylpyrrolidino-diphosphines (58).97-99 Coupling reactions with acid chlorides and related compounds have been devised which permit the facile conversion of the chelatiny diphosphine (59) into a wide variety of water-soluble diphosphines, 4.g. (a), which in the form of rhodium(1) complexes are of value as homogeneous catalysts for reactions conducted in an aqueous medium.loO A range of new chiral aminophosphines, e . g . (61), has been prepared.lol

COR (58)

g1

92 93 g4

95

96

97 913

99 1"" 101

A'

PPh

Ph lP&

HN

PPh

-PPh (59)

dNW \

so,

=PPh

(60)

G. Mlrkl, G . Yu Jin, and Ch. Schoerner. Terrahcviron Lett., 1980, 21, 1409. B. A. Arbuzov, 0.A. Erastov, and G. N . Nikonov, 110. Akad. Nauk S S S R , Ser, Khim., 1979, 2771 (Chem. Abstr., 1980, 92, 1 1 1 114). M. G. Voronkov, N. M. Kudyakov, V. M. D'yakov, V. I. Glukhikh, and R. K . Valetdinov, Dokl. Akad. Nauk SSSR, 1979,247, 609 (Chem. Absrr., 1979,91, 175 45 1 ). V. M. D'yakov, N. M. Kudyakov, and M. G. Voronkov, USSR P. 652 184 (Chem. Absrr., 1979, 91, 5352).

V. M. D'yakov, N. M. Kudyakov, M. G. Voronkov, R. K. Valetdinov, and V. I. Clukhikh Zh. Obshch. Khim., 1979, 49, 800 (Chem. Absrr., 1979, 91, 20 627). G. Markl, G. Yu Jin, and Ch. Schoerner, Tetrahedron Lett., 1980, 21, 1845. R. G. Kostyanovskii, Yu. 1. El'natanov. and Sh. M. Shikhaliev, Bull. Arad. Sci. U S S R , Diu. Chem. Sci., 1979, 28, 1470. T. Hayashi, M. Fukushima, M. Konishi, and M . Kumada, Tetrahedron Lett., 1980,21, 79. 1. Ojima and N. Yoda, Tetrahedron Lett., 1980, 21, 1051. K. Achinarni, Jpn. Kokai Tokkyo Koho 79 66672 (Chem. Absrr., 1979,91, 108 088). K. Achinami, N. Abe, and Y.Ishizuka, Jpn. Kokai Tokkyo Koho 79 160 365 (Chem. Ahstr., 1980, 92, 146 910). R. G. NUZZO,D. Feitler, and G. M. Whitesides, J . Am. Chem. Sor., 1979, 101, 3683. M. Fiorini and G. M. Giongo, J . Mol. Carol., 1979, 5 , 303.

11

Phosphiries atid Phosphoiiiirm S d t s

In recent years, efforts have been made to anchor phosphine-transition metal catalysts to polymeric supports for use as 'heterogeneous-homogeneous' catalyst systems. However, nearly all such supported catalysts have a low phosphorus content, and the phosphine function is unevenly distributed over the polymer chain. This problem has now been overcome by the polymerization of the (vinylary1)phosphines (62) to give the phosphinated polymers (63).Io2

The reaction of a-bromo-ketones with di-t-butylphosphine, followed by treatment with base, has given the new /?-keto-phosphines(64), which have been shown to co-ordinate to metals in the form of the bidentate enolate ion.lo3 Similarly, the reaction of diphenylphosphine with ethyl chloroacetate in the presence of ethylene oxide gives the phosphine (65).l o 4 Silylphosphines have been employed in a new route to such functionalized phosphines, the reaction of tris(trimethylsily1)phosphine with chloroacetic acid esters giving the phosphinoesters (66). Treatment of the trimethylsilyl ester (66; R = SiMe,) with methanol gives phosphinotriacetic acid ( 6 6 ; R = H ) in good yield and high purity. Other phosphinopolycarboxylic acids have also been prepared by this method. lo5 The synthesis and reactivities of dicyanoalkylidenephosphines, e.g. (67), which are analogues of acyl-phosphines, have been studied. Diorgano(styryl)tin chlorides react with silyl-phosphines to give the stannyl-phosphines (68).Io7 The reaction of secondary phosphines with p-dimethylaminobenzaldehyde gives the diphosphines (69).lo8 But,PCH,COR

Ph,PCH2C0,Et

P(CH 2C0,R)

(64) R = Ph or But

(65 1

( 6 6 ) R = Me, Et, Ar, or S i M e ,

,PPh2 (NC),C=C

(67) X

lo3 1

'

lo5 106

1'17 108

=

\

R1,(PhCH=CH)SnPR2,

X

Me, Et, CO,Et, or CI

(68) R' = Bu or p-tolyl or R'?=(CH,), R 2 = Ph or But

Me,N (69) R = Ph or PhCH,

A. J . Naaktgeboren, R . J. M . Nolte, and W. Drenth, J . Am. Chem. SOC.,1980, 102, 3350. C. J. Moulton and B. L. Shaw, J . Chem. SOC.,Dulton Trans., 1980, 299. A. ~ I . Razumov. R. I . Tarasova, V. G . Nikolaeva, and R. L. Yafarova, Fr. Demande 2 401 931 (Chem. Absfr., 1979, 91, 193 417). A. Tzschach and S. Friebe, Z. Chem., 1979, 19, 374. K . lssleib and H . Schmidt, Z. Anorg. Allg. Chem., 1979, 459, 131. H . Schumann, G. Rodewald. J. L. Lefferts. and J . J. Zuckerman. J . Organornet. Chem., 1980, 190, 53. H . Oehme and E. Leissring, 2. Chem., 1979, 19, 416.


12

Reactions.-Nucleophilic Attack at Carbon. Studies of the rate of quaternization of (o-NN-dimethylaminoalkyl)diphenylphosphines(70) with benzyl chloride in benzene-methanol indicate the existence of a modest degree of t hrough-space nitrogen 2p-phosphorus 3d overlap between the amino-group and the developing phosphonium centre in the transition state.logThe heterocyclic phosphine (71) undergoes quaternization with phenacyl bromide in nitromethane five times more slowly than triphenylphosphine, and almost twenty times more slowly than (0-methoxypheny1)diphenylphosphine. Stabilization of the developing phosphonium centre in the transition state by oxygen 2p-phosphorus 3d interactions of the type previously suggested by McEwen et al.llo as being involved in the quaternization of (0-methoxypheny1)phosphinesis clearly inhibited by the constraints imposed by the ring system in (71), the predominant effect of the oxygen atom being withdrawal of electrons from phosphorus. These conclusions are supported by an X-ray study of the p-bromobenzyl bromide salt derived from

Ph,P(CH ), NMe (70) II = 1-4

am '..pii."' /

\

Ph

(71)

Ph

,

0 (72)

'Ph

(71), which reveals that the transannular P . - * 0 distance is 3.1 1 A, indicating little interaction.lll Studies of the kinetics of quaternization of tributyl- and triphenyl-phosphine with a range of alkyl halides in a variety of protic and aprotic solvents have also been reported.l12 Electron-withdrawing substituents in the pyridine ring increase the rate of demethylation of pyridinium salts by triphenylphosphine in DMF. 113 Further studies of the demethylation of methylsulphonium and methylselenonium ylides, e.g. (72), by tertiary phosphines have also been r e ~ 0 r t e d .115 l~~~ Evidence has been presented which shows that the 1,2-aIkylidenediphosphoranes (73) (resulting from the reactions of dimethyl acetylenedicarboxylate and dibenzoylacetylene with a variety of tertiary arylphosphines in excess) are formed via the zwitterionic intermediates (74), which have the character of nucleophilic carbenes. These can be trapped with sulphur to give the stable ylides (75).'l6 The reaction of tris(dimethy1amino)phosphine (or of trimethyl phosphite) with dimethyl acetylenedicarboxylate in the presence of methanol as a trapping agent gives the salt-free ylides (76).l17 Tributylphosphine adds to ethoxyacetylene to W. E. McEwen, J . H . Smith, and E. J . Woo, J . Am. Chem. Soc., 1980, 102, 2746. W. E. McEwen, A . B. Janes, J. W. Knapczyk, V. L. Kyllingstad, W.-I. Shiau, S . Shore, and J. H . Smith, J. Am. Chem. SOC., 1978, 100, 7304. 111 D. W. Allen, 1. W. Nowell, and P. E. Walker, Phosphorus Sulfur, 1979, 7 , 309. 112 F. Quemeneur and B. Bariou, J . Chem. Res., 1979, ( S ) , 187, 188; ( M ) , 2344, 2357. 11s H. Alsaidi, R. Gallo, and J. Metzger, Chem. Scr., 1979, 13, 189. 114 B. A. Arbuzov, Yu. V. Belkin, N. A . Polezhaeva, and G . E. Buslaeva, Bull. Acad. Sci. USSR, Dio. Chem. Sci., 1979, 28, 1502. 115 N. N. Magdesieva and V. A . Danilenko, Zh. Obshch. Khim., 1979,49, 1978 (Chem. Ahstr., 1980.92, 58 891). 116 J . C. Tebby, I. F. Wilson, and D. V. Griffiths, J . Chem. Soc., Perkin Trans. I , 1979, 2133. 1 1 7 R. Burgada, Y . Leroux, and Y. 0. El Khoshnieh, Tetrahedron Lett.. 1980, 21, 925.

109

110


“Pk

RCO

13

(73) R = Ph or Me0

-S

RCO

RCO

J

(74)

(75)

C02Me R,P=

I

C-CHC0,Me

I

OMe (76) R = Me2N o r OMe

+

Bu ,P-C=CH OEt (77)

+

MeCOBr

____)

Bu ,P-C=CHCOMe

Lt

Br-

(7 8)

give an initial adduct, presumably (77), which can be trapped with acetyl bromide to give the salt (78).11* Nucleophilic addition of tertiary phosphines to allenecarboxylates gives the dipolar adducts (79).l19 The reaction between triphenylphosphine and the dithietan (80) affords triphenylphosphine sulphide and the ylide (81), which reacts normally with aldehydes in the Wittig reaction.120 The factors affecting the course of the reactions between perfluoroalkenes and tertiary phosphines have been elucidated.121A number of studies of nucleophilic attack of tertiary phosphines on alkenes, dienes, and arenes that are co-ordinated to a transition metal have been d e ~ ~ r i b e d . l ~ ~ - l ~ ~

(79) R’ = Ph or Me,N R 2 = Et or Me

Reports continue to appear of the reactions of primary and secondary phosphines with carbonyl compounds to form (a-hydroxyalkyl)phosphines,126 Tris(hydroxymethy1)phosphine has also been employed in similar reactions. 126s 127 11s A. M. Torgomyan, M. Zh. Ovakimyan, and M. G. Indzhikyan, Arm. Khim. Zh., 1979,32, 119 120 121 122

123 124

125 126 127

288 (Chem. Abstr., 1980, 92, 6622). R. Gompper and U. Wolf, Liebigs Ann. Chem., 1979, 1406. D. J. Burton and Y. Inouye, Tetrahedron Lett., 1979, 3397. D. J. Burton, S. Shinya, and R. D. Howells, J. Am. Chem. SOC.,1979, 101, 3689. L. Cosslett and L. A. P. Kane-Maguire. J. Organomet. Chem., 1979, 178, C17. M. Gower, G. R. John, L. A. P. Kane-Maguire, T. I. Odiaka, and A. Salzer, J , Chem. SOC., Dalton Trans., 1979, 2003. S. G. Davis, L. S. Gelfand, and D. A. Sweigart, J. Chem. SOC.,Chem. Commun., 1979, 762. A. N. Pudovik, G. V. Romanov, and V. M. Pozhidaev, Bull. Acad. Sci. USSR,Div. Chem. Sci., 1979, 28, 419. R. K. Valetdinov, A. N. Zuikova, T. A. Zyablikova, and A. V. Il’yasov, Zh. Obshch. Khim., 1979,49, 1503 (Chem. Abstr., 1980, 92, 6608). R. K. Valetdinov and A. N. Zuikova, USSR P. 662 555 (Chem. Abstr., 1979, 91, 74 706).


14

Nucleophilic Attack at Halogen. The reactions of alkyldiphenylphosphines with carbon tetrachloride in aprotic solvents give (dichloromethy1)alkyIdiphenylphosphonium chlorides and (a-chloroalky1)diphenylphosphines. Their formation is attributable to the dehydrochlorination of the intermediate dichloro(alky1)diphenylphosphoranes (82) by the ylide (83) that is also present in the system. In protic solvents, the ylides (83) are protonated while the dichlorophosphoranes (82) remain unchanged. However, the latter, on treatment with tertiary amines, are converted into the (a-chloroalky1)diphenylphosphines (Scheme 1).128 Ph (CHR ' R2)PC1,

Ph ,(CHR ' R * )P=CCl,

(82)

1

(83)

lHC'

tICI

Ph ,(CHR I R ' ) k H C I ,

Ph,PC(CI)R'R'

CI

R' = Me, Et, Pr" or Pri; R' = H or M e Scheme 1

The reaction of triphenylphosphine with carbon tetrabromide in dichloromethane solution gives the ylide (84), which undergoes alkylation with ally1 bromide to give the salt (85).129 The reaction of tris(t-buty1)phosphine with germanium tetrabromide or tin tetrabromide gives the salts (86) in almost quantitative yield.130

Applications of phosphine-carbon tetrachloride 'reagents' continue to be described. The reactions of tris(dia1kylamino)phosphines with carbon tetrachloride have been used as a source of dichloromethylene ylides, which react with aldehydes in situ to give gem-dichlorovinyl compounds. 131 Intermediate alkoxytris(dialky1amino)phosphonium salts (87), obtained from the reactions of the free hydroxylic groups in carbohydrates with phosphine-carbon tetrachloride reagents, may be reduced with lithium trialkylborohydrides to form deoxysugars, e.g. (88); see Scheme 2.132 Further examples of nucleophilic displacement (with inversion of configuration at carbon) of alkoxytris(dimethy1amino)phosphonium salts derived from carbohydrates, involving thiols 133 or azide ions 134 as the nucleophile, have appeared. The salt (89), obtainable from the reaction of 2,4,6-trimethylphenol with tris(dimethy1amino)phosphine at - 40 "C followed by treatment with sodium azide, is a convenient source of azide ions for use in the above reactions, 12* 129 130

131

132 133 134

R . Appel and M. Huppertz, Z . Anorg. Allg. Chem., 1979, 459, 7. R. H . Smithers, J . Org. Chem., 1980, 45, 173. W. W. DuMont. Z . Anorg. Allg. ChPm., 1979, 458, 85. P. A. Verbrugge and P. A. Kramer, Eur. P. Appl. 2849 (Chem. Absrr., 1980, 92, 41 431). P. Simon, J . 4 . Ziegler, and B. Gross, Synfhesis, 1979, 951. F. Chretien, Y. Chapleur, B. Castro, and B. Gross, J . Chem. SOC.,Perkin Trans. I , 1980, 381. F. Chretien, B. Castro, and B. Gross, Synthesis, 1979, 937.

Phosphines and Phosphoriium Salrs

15

Y H ,OH

Q

HO

c'-

1_

HoQoMe

OMe

OMe OMe

OMe (87)

OMe (88)

Reagents: i, (Me2N)3P, C c h ; ti, Li(HBR3)

Scheme 2

being readily soluble in organic solvents and only slightly hygroscopic; the use of the hazardous silver azide is therefore avoided. The triphenylphosphine-carbon tetrachloride combination has been used to convert 4-(hydroxymethyl)indoles into the corresponding 4-(chloromethyl)derivatives 135 and has also found applications in nucleotide synthesis. 136 The reaction of triphenylphosphine with trichloroacetamide gives a mixture of the phosphazene (90) and the salt (91); the latter is obtained as the sole product in the reaction of triphenylphosphine with trichloroacetonitrile.137

MeVO-P(NMe,), Me

c1-

Cl,CHCON= PPh

Ph 3k H ,CN

In the presence of tertiary amines, copper(1) complexes of chiral tertiary phosphines are oxidized by iodine in aqueous DMF to form the phosphine oxide with inversion of configuration at phosphorus. In contrast, phosphinites derived from the alkaloid cinchonine are oxidized with predominant retention.138 Conductimetric titrimetry indicates that iodine forms a 1 : 1 complex with triphenylphosphine, which in dioxan-THF exists as an equilibrium mixture of intimate and solvent-separated ion pairs. 139 A combination of triphenylphosphine with tri-iodoimidazole and imidazole, or alternatively with imidazole and iodine, affords a reagent that is capable of converting uic-diols into alkenes in high yield and which has found applications in the carbohydrate field.l4O9 The reactions of a-bromo-a-cyano-esters, -nitriles, and -imides with a triphenylphosphine-silver nitrate complex bring about replacement of the halogen by a nitro-group under mild conditions. 135 136

137

13R 139 140 141

142

G. S. Ponticello and J . J . Baldwin, J . Org. Chcm., 1979, 44, 4003. V. F. Zarytova, L. M. Kuznetsova, T. S. Lomakina, and W. P. Starostin, 120. Sib. Otd. Akad. Nauk SSSR, Ser. Khim. Nauk, 1979, 93 (Chem. Abstr., 1979,91, 20 953). V. P. Kukhar and E. I. Sagina, Zh. Obshch. Khim., 1979, 49, 1025 (Chem. Abstr., 1979,91,

74 676). W. Chodkiewicz, J . Organomet. Chem., 1980, 184, C61. R . Sahai, P. C. Pande, and V. Singh, Indian J . Chem., Sect. A , 1979, 18, 217. P. J . Garegg and B. Samuelsson, Synthesis, 1979, 469. P. J . Garegg and B. Samuelsson, Synthesis, 1979, 8 13. R . Ketari and A. Foucaud, Tetrahedron Lett., 1980, 21, 2237.


16

Nucleophilic Attack at Other Atoms. lnterest in the reactions of the triphenylphosphine-diethyl azodicarboxylate (DAD) ‘reagent’ continues. The stereochemical course of the conversion of 1,2-diols into 1,2-epoxides, using this reagent, has now been investigated. The optically active d i d threo-(2S, 3S)-2,3butanediol (92) is converted into the optically inactive cis-2,3-epoxybutane (93), establishing complete inversion of configuration at either one of the equivalent asymmetric carbon atoms of (92). Similarly, (S)-l,2-propanediol (94) yields predominantly (S)-1,2-epoxypropane ( 9 9 , indicating preferential regioselective attack of the reagent at the sterically less-hindered primary hydroxyl group of (94).14,A number of applications of Ph,P-DAD and the related Ph,P-di-tbutyl azodicarboxylate reagent in carbohydrate chemistry have been described, involving the formation of epoxy-sugars,14J> lJ5 the formation of ethers and esters from sterically hindered functions,146and selective conversion of allylic hydroxyl groups in alkyl hexopyranosides. l g 7 In the reactions of the 3-hydroxycarboxylic acids (96) with triphenylphosphine-DAD, activation of both the hydroxyl group and the carboxyl group has been observed. As the steric bulk of the groups R1 and R2 increases, the reagent preferentially attacks the carboxylic acid group. 14* HO OH A

Me

(94)

Me

Me

(95

A kinetic study of the Staudinger reaction of phenyl azide with various tertiary phosphines has been reported.1Js The reaction of tributylphosphine with trans-l,2-azido-alcohols,derived from cyclic epoxides, to give aziridines has now been applied to the synthesis of ‘K-region’ imines derived from polynuclear I43 144 145

146 14’ 149

V. Schurig, B. Koppenhoefer, and W. Buerkle, J. Org. Chem., 1980, 45, 538. E. Mark, E. Zbiral, and H. H. Brandstetter, Monatsh. Chem., 1980, 111, 289. H. H. Brandstetter and E. Zbiral, Helu. Chim. Acta, 1980, 63, 327. H. Kunz and P. Schmidt, Chem. Bern,1979, 112, 3886. G. Grynkiewicz, Pol. J . Chem., 1979, 53, 2501. J. Mulzer, G . Briintrup, and A. Chucholowski, Angew. Chem., Znt. Ed. Engl., 1979,18,622. Yu. G. Gololobov and L. F. Kasukhin, Zh. Obshch. Khim., 1979, 49, 961 (Chem. Abstr., 1979, 91, 107 375).

17

Phosphines und Phosphonium Salts

hydrocarbons.150Similarly, the reaction of triphenylphosphine with the asiallysubstituted azido-tosylate (97) results in the phosphonio-epimino salt (98) instead of the expected phosphinimine. This reaction does not occur if the corresponding groups are equatorially disposed. l 5 Phosphinimines derived from the reaction of triphenylphosphine with other azido-sugars and also with azidoketones have been utilized in Wittig reactions to form sugar-azomethine derivatives 152 and heterocyclic systems, 153 respectively. The reaction of triphenylphosphine with the halogenocyanomethanes (99) is reported to give the phosphinimines (100),154and the reaction with N-chloro-amidines, followed by treatment with base, forms the N-irnidoyl-iminophosphoranes(101).155 There have been several reports of the reactions of tris(dimethy1amino)phosphine with derivatives of Schiff's bases which apparently involve attack at nitrogen to give dipolar adducts such as (102).156-158 Phosphines are oxidized to the corresponding phosphine oxides o n reaction with nitronium salts in dichloromethane. Phosphorus-31 n.m.r. studies show that, at low temperatures, the nitrophosphonium salt (103) is in equilibrium with the nitrito salt (104); as the temperature is raised, this decomposes to the phosphine

I

-

I

OMe

N,

TsO- 'PPh, (98)

(97)

X,C(CN), (99) X = CI or Br

Ph,P

X

/c=c\

CN

X

/

\

(1 00)

OMe

NR'

Ph ,P=NN=PPh

,

C

4 \

R' (101) R' = Me, Et, or Ar R2= AI

o h -

PhC =C==CPh

I/

I

;/

+

R,P-NO,

PF,-

O*- N(Ph)P(NMe2), (103) (102) 150 J. Blum, I. Yona, S. Tsaroom, and Y. Sasson, J. Org. Chenz., 1979, 44, 4178. lS1 I. Pinter, J. K O V ~ C A. S , Messrner, A. Kalman, G . Toth. and B. K. Lindberg, Carbohydr.

Res., 1979. 72, 289. l a * J. KOVBCS,I. Pinier, F. Szego, G. Toth, and A. Messmer, Acra Chim. Acad. Sci. Hung., 1979, 101, 7. 153 J. Ackrell, E. Galeazzi, J. M. Muchowski, and L. Tokes, Can. J. Chem., 1979, 57, 2696. 1 5 4 V. P. Kukhar, E. I. Sagina, and N. G. Pavlenkov, Zh. Obshch. Khim., 1979, 49, 2217 (Chem. Abstr., 1980, 92, 76 602). 155 H. Yoshida, T.Ogata, and S. inokawa, Bull. Chem. SOC.Jpn., 1979, 52, 1541. 156 B. A. Arbuzov, N. A. Polezhaeva, and M. N. Agafonov, Bull. Acad. Sci. U S S R , Dic. Chrm. Sci., 1979, 28, 403. 157 B. A. Arbuzov and N. A. Polezhaeva, Bull. Acad. Sci. USSR, Dio. Chem. Sci., 1979, 28, 158 159

413. N . A. Polezhaeva, M. N. Agafonov, and B. A. Arbuzov, Bull. Acad. Sci. U S S R , Dip. Chrm. Sci., 1979, 28, 562. G . A. Olah, B. G. Balaram-Gupta, and S. C. Narang, J. Am. Chem. SOC.,1979. 101, 5317.

18


0

(105) R = H or Me

(106)

The zwitterionic adducts (105) result from the reactions of triarylphosphines with alloxan derivatives. 160 Triphenylphosphine has been used to deoxygenate various endoperoxides, e.g. ( 106), to form epoxides. l6 The reaction of diphenyl disulphide with triphenylphosphine at 250-300 'C leads to the formation of diphenyl sulphide and triphenylphosphine sulphide. Studies of the mechanism of the reaction in acetonitrile indicate the formation of ionic intermediates following nucleophilic attack of phosphorus at sulphur. Similar desulphurization reactions of sulphenyl thiocarbonates have also been reported.ls3 The combination of tributylphosphine with a disulphide gives a reagent which converts aldehydes and ketones into the corresponding dithioacetals and -ketals respectively, in high yields, under mild, neutral conditions. 164 Combinations of tributylphosphine with aryl thiocyanates have been used in syntheses of activated thiol esters 165 and arnides."j6 Full details of the syntheses of cyano-indoles, -pyrroles, and -enamines, using the triphenylphosphinethiocyanogen combination, have now appeared. 167 This reagent has also been used to prepare thioureas, acylthioureas, and amides from reactions with amines,le8 and in its reactions with Grignard reagents it provides a versatile route t o N-unsubstituted thioamides. 169 The adduct of triphenylphosphine and sulphur trioxide functions as a peptide-coupling reagent.170 A full account of studies of the transfer of selenium from phosphine selenides to tertiary phosphines has now been published. Transfer is rapid in solution, and a bimolecular process is indicated. It has been suggested that, owing to its ease of removal with the aid of a more nucleophilic phosphine, selenium is a better protecting group than sulphur for tervalent phosphorus. 171 Examples of nucleophilic attack of phosphorus at phosphorus and germanium centres have also been recorded. Thus the interaction of a n excess of trimethylphosphine with homocyclic trifluoromethylpolyphosphines (CF3P), ( n = 4 o r 5 ) has been investigated by n.m.r. techniques, and shown t o involve bimolecular attack of trimethylphosphine on the phosphine-phosphinidine W. E. Adams and N. D. Heindel, J . Heterocpcl. Chem., 1980, 17, 559. W. Adam and M . Balci, J . Am. Chem. SOC.,1979, 101, 7542. D. L. Middleton, E. G . Samsel, and ti. H . Wiegand, Phosphorus Sulfur, 1979, 7 , 339. 1 6 3 D. N. Harpp and A. Granata, J . Org. Chem., 1980, 45, 271. 1 6 4 M. Tazaki and M. Takagi, Chem. Lett., 1979, 767. 165 P. A. Grieco, Y. Yokayama, and E. Williams, J . Org. Chem., 1978, 43, 1283. 166 P. A. Grieco, D. S. Clark, and G . P. Withers, J . Org. Chern., 1979, 44, 2945. 167 Y . Tamura, M . Adachi, T. Kawasaki, H. Yasuda, and Y . Kita, J . Chem. SOC.,Perkin Trans. 1, 1980, 1132. 168 Y. Tamura, T. Kawasaki, M. Adachi, and Y. Kita, Chem. Pharm. Bull., 1979, 27, 1636. 169 Y. Tamura, T. Kawasaki, M. Adachi, and Y. Kita, Synthesis, 1979, 887. 170 I . J . Galpin, C. W. Kenner, and A. Marston, Bioorg. Chem., 1979, 8, 323. 1 7 1 D. H. Brown, R . J . Cross, and R. Keat, J. Chem. SOC.,Dalton Trans., 1980. 871.

160 161

l62

19


(109) X = C1 or Br

(108)

complex (107) via a transition state of type (108).172Trihalogenogermyldi(tbuty1)phosphines combine with germanium(I1) halides to form the mixed-valence germanium-phosphorus ylides (109).173 Miscellaneous Reactions. Reactions leading to the formation of 'methylenephosphines', involving P(3pn)-C(2p,) n-bonding, continue to appear. Aromatic primary phosphines combine with carboxylic amide acetals to give (1 Such dico-ordinate tervalent phosphorus compounds often arise in the reactions of silylphosphines with carbonyl and related compounds. Thus the reaction of phenylbis(trimethylsily1)phosphine with D M F gives (110; Ar = Ph, R = H) 175 and the reaction with carbon disulphide forms (111).176Compounds of the type (1 12) are formed in the reactions of t-butylbis(trimethylsily1)phosphine with a range of acid ch10rides.l~~ The compounds (113) are among the products of the reactions of bis-silylated phosphines with carbodi-imides; 178 with isocyanide dichlorides, compounds of the type (114) are formed, along with other products. l7s la0The reactions of bis-silylated phosphines with oxalyl chloride lead to the four-membered-ring compounds (115),lS1and a similar product has also been isolated in a related reaction with phosgene.ls2 In each case, it is likely that 9

ArP =C(R)NMe,

PhP-

(110) R = H or Me Ar = Ph or mesityl

C(SSiMe,),

ButP=C(R)OSiMe, (112) R = Me, hi,CF,, or C0,Et

(1 11)

RNSiMe,

I

Me,SiO OSiMe,

M

phP/','PPh R'P =C[ N(RZ)SiMe,I, (113) R', RZ= alkyl or aryl

I

PhP\

,PPh C'

I

RNSiMe,

RP-PR

(115) R = But or Ph

(1 14) R = aryl 172 173 174 175

176 177

178 179

180 181 182

A. H . Cowley and M. C. Cushner, Znorg. Chem., 1980, 19, 515.

W.-W. DuMont and G . Rudolph, Znorg. Chim. Acta, 1979, 35, L341. H. Oehme, E. Leissring, and H. Meyer, Tetrahedron Lett., 1980, 21, 1141. G . Becker and 0. Mundt, 2. Anorg. Allg. Chem., 1980, 462, 130. G . Becker, G. Gresser, and W. Uhl, 2. Anorg. Allg. Chem., 1980, 463, 144. 0. I. Kolodyazhnyi and V. P. Kukhar, Zh. Obshch. Khim., 1980, 50, 233 (Chem. Abstr., 1980, 92, 181 291). K. Issleib, H.Schmidt, and H. Meyer, J. Organomet. Chem., 1980, 192, 33. R. Appel, V. Barth, F. Knoll, and I. Ruppert, Angew. Chem., Znt. Ed. Engl., 1979,18,873. R. Appel and B. Laubach, Tetrahedron Lett., 1980, 21, 2497. R. Appel and V. Barth, Tetrahedron Lett., 1980, 21, 1923. R. Appel, V. Barth, M. Halstenberg, G. Huttner, and J. von Seyer, Angew. Chem., Znt. Ed. Engl., 1979, 18, 872.

20


CO,Me But P(Cl)CH(CO,Me) ,

tt,N

+

BufP=C(CO,Me),

_+

Bu'p+co2Me / 0, /But

P=C compounds are involved as intermediates. The halogenophosphine (1 16) undergoes dehydrochlorination in the presence of triethylamine to form (1 17), which is reported to dimerize to form (1 1S).la3 Studies of the formation and reactions of very simple met hylenephosphines and related phospha-alkynes (containing the P-C linkage) have ~ o n t i n u e d . ~ ~ ~ - ~ ~ ~ Examples of insertion reactions involving Si-P and Ge--P bonds continue to appear. The Si-P bond of diphenyl(trimethylsily1)phosphine is easily attacked by electrophilic heteroallenes such as carbon disulphide or iso(thio)cyanates to give insertion products, e.g. (1 19).lSAStudies using heterocyclic compounds of known configuration at silicon or germanium have shown that such reactions proceed with retention of configuration at the Group IV atom, indicating the probable involvement of a four-centre concerted r n e c h a n i ~ m . ~l g~o~Insertion 9 of phenylphosphinidine, CBHBP : (obtained from the thermal decomposition of cyclopolyphosphines) into 2-sila- or 2-germa-phospholans leads to a new class of cyclic compounds (120).lg1 Insertion and other reactions of the first silaphosphetan (121) have also been described.lg2 X

I1

Me,SiN(R)CPPh, (1 19) R = Ph or Me

X=OorS

Php-pPh Me,h4> (120) M = Si or Ge

Me,Si-PPh

LA

(121)

In continuation of studies of the metallation of (o-halogenobenzyl)phosphines, it has now been reported that the lithiated compound (122), obtained from the related (o-bromobenzy1)phosphine with butyl-lithium, may be isolated as a solid, and used subsequently for the preparation of a range of cyclometallated 183 184

185 188

0. I . Kolodyazhnyi, Zh. Ohshc,h. Khim., 1980, 50, 230 (Chem. Abstr., 1980. 92, 181 289). H . Eshtiagh-Hosseini, H. W. Kroto, J . F. Nixon, and 0. Ohashi, J . Organomct. Chem., 1979,181, C1. N . P. C . Westwood, H . W . Kroto. J . F. Nixon, and N. P. C . Simmons, J . ChcJm.Soc., Dalton Trans., 1979, 1405. T. A. Cooper, H . W. Kroto, J . F. Nixon, and 0. Ohashi, J . Chem. Soc., Cht.m. Commirn., 1980, 333.

187

188 189 190

191 192

H . Eshtiagh-Hosseini, H . W. Kroto, J . F. Nixon, S. Brownstein, J. R . Morton, and K . F. Preston, J . Chem. SOC.,Chem. Commun., 1979, 653. U. Kunze and A. Antoniadis, Z . Annrg. Allg. Chem., 1979, 456, 155. J . Dubac, J . Cavezzan, P. Mazerolles, J . Escudie, C . Couret, and J . Satge, J . Organomrr. Chem., 1979, 174, 263. J. EscudiC, C. Couret, J . Dubac, J. Cavezzan. J . SatgC, and P. Mazerolles, Tetruherfron Lett., 1979, 3507. J. Escudie, C. Couret, and J. SatgC, Recl. Trui>.Chim. Pays-Bas, 1979, 98, 461. C. Couret, J. EscudiC, J . Satge, J. D. Andriamizaka. and B. Saint-Roch, J . Organornet. Chem., 1979, 182, 9.

Phosphhi~sand Phosphoiiirrm Solts

21 Ph

transition-metal compounds.1Y3Lithiation of [bis(trimethylsilyl)methyl]diphenylphosphine gives (123), which behaves as the lithium salt of a phosphorane anion and which has been used to prepare a range of double ylides that are of potential interest as chelating agents.lY4 Cyclometallation has often been observed among metal complexes of bulky tertiary phosphines and, not surprisingly, trimesitylphosphine has now been shown to form cyclometallated derivatives.195However, it has recently been reported that the relatively non-bulky dimethylphenylphosphine also undergoes cyclometallation by iridium, but at the orrho-position of the phenyl ring rather than at the methyl group.1y6On heating under reflux in benzene or toluene, cis square-planar bisphosphine-platinum or -palladium complexes derived from (phenylethyny1)diphenylphosphine are converted into isomeric complexes of the new unsymmetrical diphosphine ( 124).ly7Nucleophilic addition of co-ordinated sulphur to (alkynyl)phosphines, giving a synthesis of anionic 1-phosphino-2sulphido-alkene ligands, has also been reported.]!'* A number of papers have appeared which are concerned with the cleavage of P--C bonds of phosphines that are co-ordinated to transition metals.1s9--'04 Photochemical reactions of a range of orrho-substituted benzoyldiphenylphosphines have been r e p ~ r t e d"06 .~~ ~~ Phosphonium ylides and triphenylphosphine oxide are formed upon irradiation, with long-wavelength U.V.light, of a series of diary1 and aryl alkyl ketones in the presence of triphenylphosphine.'07 Kinetic studies of the attack of alkoxyl radicals on triphenylphosphine have provided the first absolute measurements on these processes, which lead to the formation of alkoxytriphenylphosphoranyl radicals; these have now been conclusively characterized by optical spectroscopy. " 0 8 Abstraction of H.-1'. Abicht and K. Issleib, J . OrgunotiicJt. C'hctii., 1980, 185, 265. R . Appel and G . Haubrich, Attgev*. Chrm., Int. Ed. Etigl., 1980, 19, 213. I y 5 S. A . Dias and E. C . Alyea, Trunsrtion M c t . CliiJt?r. (Wc~inhcitii,Ger.), 1979, 4, 205. l'J(i K. H . Crabtree, J . M . Quirk, H. Felkin, T. Fillebecn-Khan, and C. Pascard, J . Orguiionict. CIi(,ui., 1980, 187, C32. 1u7 A . J . Carty, N . J . Taylor, and D. K . Johnson, J . Ani. Clivtn. SOL'., 1979, 101, 5422. A . J . Carty, F. Hartstock, N . J . Taylor, H . Le Bozec, P. Robert, and P. H . Dixneuf, J . Chi~tii.Soc., Chenl. Conii?iun., 1980, 361 . I99 M. Michman, V . R. Kaufman, and S. Nussbaum, J. O r , p n o i w t . Chcnt.,1979, 182, 541. wU S. Nussbaum and M . Michnian, J. Organonict. Chctu., 1979, 182, 555. 201 K. Kaneda, K. Sano, and S. Teranishi, Clrclm. L ~ t t . ,1979, 821. 2~ K. Kikukawa. T . Yaniane, Y . Ohbe, M . Takagi, and T . Matsuda, Bull. Chclni. SOC.J p i i . , 1979, 52, 1187. 203 K. Kikukawa, M . Takagi, and T. Matsuda, Bull. Choir. SOL'.Jpn., 1979, 52, 1493. 2 o j M. Lewin, Z . Aizenshtat, and J . Blum, J. Orgrrnomet. Chi>tii., 1980, 184, 255. 2 0 5 M. Dankowski, K . Praefcke, S. C . Nyburg, and W. Wong-Ng, Phosphorus Suwur, 1979, 7 , 275. 2('6 M . Dankowski and K. Praefcke, Phosphorus Sulfur, 1980, 8 , 105. ~7 M . A . Fox, J . Am. Clicm. Suc., 1979, 101, 5339. 2"s D . Griller, K . U . Ingold, L. K . Patterson, J . C. Scaiano, and R . D. Small, Jr. J . Ant. Chewi. Such., 1979, 101, 3780. lY3

2

22

Organophosphorus Chemistrj,

hydrogen atoms from diphenylphosphine by stable radicals has been studied and shown to proceed uiu a synchronous S s 2 free-radical mechanism.20g Tertiary phosphines are readily converted into their oxides by p-chlorobenzeneselenonic acid,210 by chromium( v) compounds,21 and by carbon dioxide in the presence of rhodium complexes. " Dialkyl[bis(methoxycarbonyl)methyl]phosphines have been shown to be involved in a tautomeric equilibrium with ylides having a P-H

2 Phosphonium Salts Preparation.-The first synthesis has been reported of the extremely crowded tetra-t-butylphosphonium cation. An X-ray study shows that the P-C bonds A wide are elongated and the bond angles about carbon are range of (branched a1kyl)triphenylphosphonium salts (1 25) has been prepared and used in the synthesis of insect The reaction of triphenylphosphine with trimethylsilylmethyl triflate gives the salt (126); on treatment with caesium fluoride in acetonitrile, this affords the related silylated ylide.216 The tritylphosphonium salt (127) is formed in the reaction of trimethylphosphine with trityl tetrafluoroborate in n i t r ~ m e t h a n e . ~The ~ ' (oxoalky1)phosphonium salts (128), formed in the reactions of triphenylphosphine with ap-unsaturated ketones in the presence of hydrogen bromide, could be regarded as synthetic equivalents of B-acylethyl and B-acylvinyl anions, However, they cannot be used for the generation of ylides, since on treatment with base they either dissociate into starting materials by a Hofmann elimination or undergo intermolecular cyclization of the intermediate ylide. For these reasons, they have been converted

BF,

(125) R' = Me, Et, Pr, or C , H , , R'= Me, Et, Pr, Bu, o r C , H , , n = 1-3 Ph , k P . ' R 'CH $OR

Br -

(128) R', R 2= H, Me, o r Ph R' = Me or P h

209 210

211 212 213

214

215 216 217

(1 27)

Ph ,bCR R T O S( 1 2%

R'X

Ph &R' R ZCOSR ' X (130) X = C1 or 1

R ' = H, Me, Pr, or PhCH,CH, R 2= H, Me, o r Et R 3= Me, Et, or PhCH,

Yu. G . Shermolovich, A . V. Misyura, 0. M . Polumbrik, and L. N . Markovskii, D O ~ O U . Akad. Nauk Ukr. R S R , Ser. B, 1979, 449 (Chem. Abstr., 1979, 91, 140014). L. G. Faehl and J . L. Kice, J . Org. Chem., 1979, 44, 2357. K. F. Miller and R. A . D. Wentworth, Inorg. Chim. Acta, 1979, 36, 37. K. M. Nicholas, J . Organomet. Chem., 1980, 188, CIO. 0. I . Kolodiazhnyi, Tetrahedron Lett., 1980, 21, 2269. H. Schmidbaur, G. Blaschke, B. Zirnmer-Gasser, and U . Schubert, Chem. Ber., 1980, 113,1612. H. J. Bestmann, P. Rosel, and 0. Vostrowsky, Liebigs Ann. Chem., 1979, 1189. E. Vedejs and G. R . Martinez, J . A m . Chem. SOC.,1979, 101, 6452. R . A. Jones, G. Wilkinson, M. B. Hursthouse, and K . M. Abdul Malik, J . Chem. Soc., Dalton Trans., 1980, 117.

23


into the corresponding acetals and thioacetals for use in 2 1 9 The reaction of yiides with carbonyl sulphide gives the betaines (129),which may be alkylated to give the salts (130), electrolysis of which yields thiolesters,220 Treatment of the bromo-enol ethers (1 31) with triphenylphosphine in nitromethane gives the salts (132); on treatment with dilute acid, followed by sodium carbonate, these afford 2-oxocycloalkylidenetriphenylphosphoranes (1 33), as shown in Scheme 3.221

Me0

Me0

(131)n = 1 or 2

0

( 1 33)

(132)

Reagents: i, PhsP, MeN02; ii, HCI; i i i . NazC03

Scheme 3

Full details have now appeared of the reactions of tropylium salts with stabilized phosphonium ylides, giving the salts (1 34).222 Decarboxylation of (1 34; R = OH)affords (135), which on heating at 155 "C in D M F or DMSO undergoes conversion into a mixture of isomeric (cycloheptatrienylmethy1)phosphonium salts. Hydride abstraction from (1 35) yields (1 36), which is a very strong acid, being deprotonated by water to give a stable ~ l i d e . ~ ~ ~

OYR /

BF4-

o C H 2 i P h , /---

+PPh,

( i../ -.. l l .t. C H 2 ~ P h 3

BF,-

2BF4

(134) R = Ph, OMe, or OEt

(135)

(136)

(137) R = Ph or But

(1 38)

( 1 39)

The reaction of triphenylphosphine with gem-dichlorocyciopropenesgives the salts (1 37); on treatment with antimony pentachloride, these are converted into the phosphoniocyclopropenylium salts (1 38). 2 2 4 The cyclopropylphosphonium salt (1 39) is formed in the reaction of (3-bromopropyl)triphenylphosphonium bromide with sodium ethoxide.225 H-J. Cristau, J-P. Vors, and H. Christol, Synthesis, 1979, 538. H-J. Cristau, J-P. Vors, and H. Christol, Tetrahedron Lett., 1979, 2377. 2~ H. J. Bestmann and H. Saalbaum, Bull. SOC.Chim. Belg., 1979, 88, 951. 221 E. Ohler and E. Zbiral, Chem. Ber., 1980, 113, 2326. 222 G. Cavicchio, M. D'Antonio, G. Gaudiano, V. Marchetti, and P. P. Ponti, Guzz. Chim. Ital., 1979, 109, 315. 2 z 3 G. Cavicchio, G . Gaudiano, and P. P. Ponti, Terrahedron Lerr., 1980, 21, 2333. 224 R. Weiss, C. Priesner, and H. Wolf, Angew. Chem., Int. Ed. Engl., 1979, 18, 472. m M . I . Komendantov, T. K. Klindukhova, G. N. Suvorova, and M . V. Eremenko, Zh. Org. Khim., 1979, 15, 2076 (Chem. Abstr., 1980, 92, 93 924). 218

219

24

0rganophosphoru.s ChcJmistrj~

The synthesis of biaryls tlia the reactions of triethylphosphine complexes of arylnickel(I1) halides with aryl halides is accompanied by the formation of aryltriethylphosphonium halides.226Analyses of the products from the nickel(I1)bromide-catalysed arylation of diphenylchlorophosphine, diethylaminodiphenylphosphine, and diphenylthiophosphinite esters indicate that pseudophosphonium salts are actually formed in each case. However, only the aminophosphonium salts are stable under the reaction conditions, the others undergoing a variety of transformations. Arylation of diphenylphosphine under similar conditions leads to the formation of diaryldiphenylphosphonium Aryl- and heteroaryltriphenylphosphonium salts may also be formed, however, simply by heating together certain bromo-aromatic or heteroaromatic compounds with triphenylphosphine at temperatures between 200 and 3 0 0 'C, in the absence of a nickel halide 2 2 9 The electrolytic oxidation of tertiary phosphines in the presence of arenes or heteroarenes also leads to aryl- or heteroaryl-phosphonium salts in good yield.230Similarly, electrolytic oxidation of triphenylphosphine in acetonitrile containing primary alcohols or dialkyl disulphides yields alkoxyand alkylthio-triphenylphosphoniumsalts. 231 Studies of the formation of phosphonium salts from 2-bromoethoxycarbony1 derivatives of amino-acids and similarly protected alcohols, phenols, and secondary amines have The same group has also explored the use of the phosphonioacetyl protecting groups in peptide There has also been considerable interest in the preparation of phosphonium salts bound to polymeric supports, these systems having potential as phase-transfer catalyst^.^:^^-^^^ The preparation, structure, and reactivity of two-co-ordinated phosphorus-containing cations (phosphenium ions, R2P+) have been reviewed.239The reactions of hexamethylphosphoric triamide (HMPT) with acid chlorides or anhydrides in the presence of antimony pentachloride have given the first moderately stable (acy1oxy)phosphonium salts.240

Reactions.--A lkaline Hydrolysis. Continuing their studies of t hrough-space oxygen 2p-phosphorus 3d interactions, McEwen's group has now shown that the relative rates of alkaline hydrolysis of the salts (140; Z=OMe, X = I ) are dominated by the inductive electron-withdrawing effects of the methoxy-group T. T. Tsou and J . K . Kochi, J . Am. Chem. Soc., 1979, 101, 7547. H-J. Cristau, A. C h h e , and H . Christol, J . Organomet. Chem., 1980, 185, 283. 228 M . 1. Shevchuk, I . V. Megera, and 0. M . Bukachuk, Zh. Obshch. Khim., 1979, 49, 1225 (Chem. Abstr., 1979, 91, 108 052). 2 2 9 0. M. Bukachuk, 1. V. Megera, M. I . Porushnik, and M . I . Shevchuk, Zh. Obshch. Khim. 1979,49, 1552 (ChPm. Abstr., 1979, 91, 157 817). 230 Y u . M. Kargin, E. V. Nikitin, 0. V. Parakin, G . V . Romanov, and A . N. Pudovik, Phosphorus Siiljiur, 1980, 8, 55. 231 H . Ohmori, S. Nakai, M . Sekiguchi, and M . Masui, Chem. Pharm. Bull., 1980, 28, 910. m H-H. Bechtolsheimer, M. Buchholz, and H. Kunz, Leibigs Ann. Chem., 1979, 1908. 233 H . Kunz and H. Kauth, 2. Naturforsch., Teil. B, 1979, 34, 1737. 234 M . S. Chiles and P. C . Reeves, Tetrahedron Lett., 1979, 3367. 2 3 5 H. Molinari, F. Montanari, S. Quici, and P. Tundo, J. Am. Chem. Sur., 1979, 101, 3920. 236 S. L. Regen and J. J . Besse, J . Am. Chem. SOC.,1979, 101, 4059. 237 P. Tundo and P. Venturello, J . Am. Chem. SOC.,1979, 101, 6606. 2338 P. Tundo and P. Venturello, Tetrahedron Lett., 1980, 21, 2581. 239 A . H . Cowley, M . C . Cushner, M. Lattman, M . L. McKee, J . S. Szobota, and J . C . Wilburn, Pure Appl. Chem., 1980, 52, 789. 230 H . Teichmann, C. Auerswald, and G. Engelhardt, J . Prakr. Chem., 1979, 321, 835.

227

25

Phospliiires ntid Phosphotiiirm Suits

that is bound to saturated carbon, which are of sufficient magnitude to mask any possible effects of 2p-3d overlap. In contrast, however, rate data for the alkaline hydrolysis of the related (o-dimethylaminoalkyl)phosphonium salts ( 140; Z = NMe,, X = Br) indicate the operation of a pronounced through-space 2p-3d interaction.lo9 The electron-withdrawing effects of the oxygen, sulphur, or sulphone grouping in the six-membered ring of (141) cause these salts to undergo alkaline hydrolysis, with cleavage of a ring-phosphorus bond, significantly faster than methyltriphenylphosphonium iodide. The most marked effect, as expected, is observed for the sulphone system, which undergoes hydrolysis some lo9 times faster than the acyclic salt. These results have also aided an understanding of the course of decomposition of the related cyclic phosphonium betaines (142).241 Alkaline hydrolysis of the seven-membered-ring phosphonium salt (143 ; R = Ph) proceeds with cleavage of the exocyclic phenyl group at a rate fifty times faster than that observed for the ring-opening hydrolysis of the related salt (143; R = Me). Comparison of the rate data and activation energies for hydrolysis of these salts with those for methyltriphenylphosphonium iodide and dimethyldiphenylphosphonium iodide indicates the existence of a 'sevenmembered ring effect', which may be due to the preferentia: occupation by the ring of diequatorial positions in intermediate trigonal-bipyramidal phosphoranes. Hydrolysis of the salts (143) proceeds much more slowly than those of related five-membered-ring dibenzophospholium salts, indicating that relief of ring strain when a phosphorane is formed is of little importance for the sevenmembered-ring compounds.242This conclusion is supported by an X-ray study of the cyclic phosphine oxide (144) which reveals that the endocyclic angle at phosphorus is 107 '.243 The course of alkaline hydrolysis of the salts (145) depends on the nature of the heteroatom. When X is oxygen, cleavage of a phenyl group occurs, but when X is sulphur, cleavage of the thioether grouping occurs, presumably as a result of the greater stabilization of the carbanion that is being formed, owing to the

I

Ph,kCH,),,ZxCH ,Ph (140) Z = OMe or NMe, X = I or Br ? 1 = 1-4

a;na;D / \

Ph

Me

Ph'

1-

(141) X = 0, S, or SO,

O/CHPh (142) X = 0 , S, or SO,

(145) "11 2.1:

313

'CH,

X = 0 or S

D. W. Allen, B. G . Hutley, and A. C. Oades, 2. Nmturfiwscfi., T(Jil. B , 1979, 34, 1112. D. W. Allen, B. G . Hutley, and A. C. Oades, J . Cfiem. Soc., Pcrliin Trans. I , 1979, 2326. D. W . Allen, I . W . Nowell, and P. E. Walker, Z . Narurfiwsch., Teil. B, 1979, 35, 133.

26

Organophosphorus Chemistrji

effects of the neighbouring sulphur atom.254The cleavage of phenyl groups that occurs when macrocyclic bisphosphonium salts undergo alkaline hydrolysis has been used to prepare related macrocyclic bisphosphine oxides.245 Tris-(2-~yanoethyl)phosphinehas been converted into the functionalized phosphine oxides (146) via a sequence of quaternization and alkaline hydrolysis reactions.24sHydrolysis of the salts (147) with various bases gives the phosphine ( 148).247 RP(0)(CH2CH2C02H), (146) R = Me or Et

(MeO,CNHCH,),i C1-

+

(MeO,CNHCH,),P

(147)

(148)

Additions to Unsaturated Phosphonium Salts. Full details of the use of vinyland isopropenyl-triphenylphosphonium salts as reagents for the bicycloannulation of cyclohexenones have now appeared. These salts react with the a-enolates of a variety of a-cyclohexenones to give low to moderate yields of tricyclo[3.2.1 .02~7]octan-6-ones, and an example of their use in the synthesis of a natural product has been given.248 Addition of amidines to (2-acy1vinyl)phosphonium salts gives the (imidazolylmethy1)phosphonium salts ( 149).249The salt (1 50) undergoes addition of sodium hydrogen sulphide to give the stabilized ylide (151), from which (heteroary1)phosphonium salts can be obtained by alkylation at sulphur or protonation at carb ~ n The . ~reaction ~ ~ of aqueous ammonia with the salt (152) gives the heterocyclic saIt (153); on oxidation with perchlorate, this is converted into the stable R

W

R

Ph ,PC =CCl

N v N H XR2

I

NHCOPh

(149) R 1 = H, alkyl, or phenyl R2 = Ii, SO,Il, CCl,, CBr,, or E t 0 , C

PPh ,

S

(150)

(151)

Ph +

Ph

+

H ,PPh

Ph

Ph

Ph

c10;

Ph,P(CH=CMe), (152)

H (153)

244

~5 246 047 248

"48 250

C. G. Kruse. E. K . Poels, and A. van der Gen, J . Org. Chem., 1979,44, 291 I . H . Christol, H-J. Cristau, F. Fallouh, and P. Huliot, Tetrahedron Lett., 1979, 2591. G. W . Wilson, US P. 4 149 014 (Chem. Absrr., 1979, 91, 20 720). A. W. Frank, US P. Appl. 964 751 (Chem. Abstr., 1979, 91, 157 894) R . M. Corey, D. M . T. Chan, Y . M . A . Naguib. M. H. Rastall, and R . M . Renneboog, J . Org. Chem., 1980, 45, 1852. C. S. Labaw, R . L. Webb, and G . R. Wellrnan. Ger. Offen. 2 805 221 (Chem. Abstr., 1978. 89, 197 717). 0. S. Drach, 0. P. Lobanov, and A . P. Martynyuk, Zh. Obshch. Khim., 1979, 49. 7 17 (Chem. Absrr., 1979, 91, 20 620).

27

Phosphines and Phosphonium Sctlts

nitroxide radical (154). The latter, on alkaline hydrolysis, loses an exocyclic phenyl group and is converted into a related heterocyclic phosphine oxidenitroxide A wide variety of acyclic and heterocyclic adducts have been prepared by nucleophilic addition to phenylethynyltriphenylphosphonium bromide. 2 5 2 Miscc4luneous Reactions. The reactivity of alkylthio- and alkylseleno-phosphonium salts towards nucleophiles has been used to achieve the first stereospecific synthesis of a chiral phosphinite, and also for the synthesis of chiral phosphines. Nucleophilic attack at sulphur or selenium occurs when the salts (1 5 5 ) and (156) are treated with ethyl mercaptide anion to give (157) and (158) respectively, with essentially complete retention of configuration at phosphorus. SMe

I

Ph

I

P'

But,,'l'OMe SeMe

CF,SO, (156)

Nucleophilic attack at phosphorus is minimized by the presence at this atom of a t-butyl group.253Attack at sulphur is also involved in the reactions of allyl(alky1thio)phosphonium salts with dry tetrabutylammonium cyanide in methylene chloride. Under the same conditions, the related allyl(a1koxy)phosphonium salts undergo Arbuzov reactions, while allyl(diethy1amido)phosphonium salts undergo displacement of the ally1 group to form phosphinous amides with retention of configuration at phosphorus. Allyl- and benzyl-(diethy1amido)phosphonium salts also undergo cathodic cleavage of the allyl or benzyl group with retention of configuration at p h o s p h o r u ~ . ~In~ related ~ - ~ ~ ~work, the course of electroreduction of a wide range of phosphonium salts that have one or more oxygen, sulphur, or nitrogen atoms attached to phosphorus has been Cathodic cleavage of the t-butyl group from the salts (159) also occurs with retention of configuration at phosphorus to give (160).258Studies have been reported of the J . Skolirnowski, R . Skowronski, and M. Simalty, Tetrahedron L e f t., 1979, 4833. N. Morita, J . I . Dickstein, and S. I . Miller, J . C h ~ mSoc., . Perkin Trans. I , 1979, 2103. 253 J . Omelanczuk and M. Mikolajczyk, J . Am. Cl7em. Soc., 1979, 101, 7292. 2 5 4 L. Horner and M. Jordan, Phosphorus Sulfur, 1979, 6 , 491. 2c)5 L. tlorner and M. Jordan, Phosphorus Sulfur, 1980, 8, 2 1 5 . x)+i L. Horner and M. Jordan, Phosphorus Sulfur, 1980, 8, 225. "9' L. Hoqner and M. Jordan, Phosphorus Sulfur, 1980, 8, 209. 2~ S. Samaan, Phosphorus Sulfur, 1979, 7 , 89. 251

252

28

Organophosphorus C'hcmistrjg

Me

Me

(159) X = 0, S, or NMe

(160)

preparative-scale electrolytic reduction of benzyl-, allyl-, cinnamyl-, and polyenyl-phosphonium salts, leading to hydrogenolysis and radical-coupling produ c t ~The . ~ reaction ~ ~ of the benzyltriphenylphosphoniumion in aqueous solution with electrons that were generated by radiolysis of the solvent also results in the formation of bibenzyl, together with triphenylphosphine.260The polarographic reduction of a series of (heteroary1)- and (heteroarylmethy1)-phosphonium salts has been studied, using a differential pulse technique, this having a number of advantages over classical d.c. polarography. For the salts (161), the observed order of ease of reduction correlates with the electron-withdrawing ability of the heteroaryl group (i.t.. 2-fury1 > 2-thienyl~phenyl> 1-rnethylpyrrol-2-y1), whereas for the salts (162) the ease of reduction correlates best with the order of stability of the carbanions that are being formed, as established in earlier studies of the alkaline hydrolysis of these salts.261Polarographic reduction of the salts (163) occlfrs in two single-electron stages." G 2

[

Q$Pc::Ph

(161) X = 0 , S, CH=CH,

Ph3PCH2QY or NMe

( 1 6 2 ) X = 0, S, NMe, or CH=CH Y = Br or 1

(163) R = H, F, Br, Me, M e O , M e 2 N , or N O ,

The P-triorganostannylphosphonium salts ( 1 64) undergo heterolytic fragmentation on thermal decomposition.2G"* 264 The salts (165), obtained from the reactions of triphenylphosphine with 0-protected or-bromo-ketoximes, can be deprotected under very mild conditions to give the salts (166), which are useful ~ ~ ~ of the hydrolysis and intermediates for the synthesis of l - a z i r i n e ~ .Studies 267 methanolysis of (ary1oxy)phosphonium salts have 259

263 "63 26.1 255

266 267

J. H . P. Utley a n d A. Webber, J. Chcni. Soc., Perhiti Trans. I, 1980, 1154. H. Horii, S. Fujita, T. Mori, a n d S. Taniguchi, B d l . Chem. SOC.Jpn., 1979, 52, 3090. D. W . Allen a n d L. Ebdon, Phosphorus Siclfiir, 1979, 7, 161. S. 1. Petrov, V. N. Abramov, a n d L. A. Kazitsyna, Zh. Obshcli. Kliim., 1979, 49, 376 (Chetrt. Ahstr., 1979, 91, 4805). D. Seyferth, K. R. Wursthorn, a n d R. E. Maniniarella, J . Organornet. Client., 1979, 179, 25. H. Weichmann, G. Quell. a n d A . T'zschach, Z. Anorg. AIIg. Clienr., 1980, 462, 7. A. Hassner a n d V. Alexanian, J. Org. Cliem., 1979, 44, 3861. S. J. Kubisen, Jr., a n d F. 13. Westheimer, J . A m . Clienr. Soc., 1979, 101, 5985. S. J . Kubisen, Jr.. a n d F. H. Westheimer, J. Am. Cliem. Soc., 1979, 101, 5991.

Phosphities and Phosphonium Suits

29

R' ,SnCH,CH,PR2, I (164)

-+

R',SnI + H,C =CH,

+

R 23P

R' = Me, Bu, or Ph R 2= Me,Et, Bu, or Ph Br-

Br

NOH

(166)

'R

(165)

3 Phospholes and Phosphorins Compared with the previous year, there has been a noticeable reduction in the number of papers in this area. Developments over the past few years in the chemistry of phospholes and phosphindoles, covering synthesis, reactivity, and the aromaticity problem, have been reviewed."* Full details have now appeared of the synthesis, reactivity, and structure of 1 , l '-diphosphaferrocenes. Routes to these compounds have been improved by the use of the sodium-naphthalene radical anion reagent for the cleavage of phosphorus-phenyl bonds of the phenylphospholes (167), followed by conversion of the resulting sodium phospholide into the magnesium derivative (168) by treatment with anhydrous magnesium bromide (Scheme 4). The reaction of (168) with iron(r1) chloride

I,

Ph (167)

R = H or Me

R

ii

R

-k-Q MgBr (168)

(16%

Reagents: i. Na, C I O H Ri i;, MgBr.; i i i , FeCls

Scheme 4

gives the diphosphaferrocenes (169) in high yield. An X-ray study has shown that (169; R = Me) has the expected sandwich metallocene structure. The phospholyl rings of these compounds readily undergo Vilsmeier formylation and Friedel-Crafts acylation reactions. However, attempts to metallate the ring systems using butyl-lithium failed, and a general sensitivity to nucleophilic media was noted.2seThe magnesium derivatives (168) have also been employed in the synthesis of some zirconium compounds containing n-co-ordinated phospholide ring systems. 370 The a-bonded phospholyl-manganese complex (170) is converted (on heating) into the phosphacymantrene (171), and related rhenium and iron compounds behave similarly.271The electronic structure of phosphacymantrenes has been studied by photoelectron spectroscopy and EHT calculations, the z 6 8 A. N .

Zio

Z7I

Hughes, Stud. Org. Chem. (Amsterdam), 1979, 3 (New Trends Heterocyclic Chem.), p. 216. G . de Lauzon, B. Deschamps, J . Fischer, F. Mathey, and A. Mitschler, J . A m . Chem. Suc., 1980, 102, 994. P. Meunier and B. Gautheron, J . Organomet. Chrm., 1980, 193, C l 3 . E. W. Abel, N. Clark, and C. Towers, J . Chem. SOC.,Dcllron Trans, 1979, 1552.

2*

30

Organophosphorus Chemistrj.

' P

P h y

Ph - __

(170)

(171)

results being consistent with the phospholyl ring system having aromatic character.272Palladium complexes containing n-bonded electrically neutral phosphole ligands have been prepared from a range of simple p h o ~ p h o l e s . ~ ~ ~ Interest in the chemistry of azaphospholes, involving two-co-ordinate phosphorus in a cyclic delocalized n-system which also includes sp 2-hybridized nitrogen, continues. Full details have now appeared of the synthesis and reactions of the 1,2,3n2-diazaphospholes (172), which are readily accessible from the reactions of phosphorus trichloride with substituted hydrazones derived from acetone. These heterocycles undergo metallation at nitrogen rather than at The diazaphosphole ( 173) co-ordinates to metal carbonyls via phosphorus, and not cia the pyridine-like nitrogen atom.275An X-ray study of the triazaphosphole (174) shows that both phosphorus-nitrogen distances are identical, implying that a pn-pn delocalized system is Thermal decomposition of the phosphorane (1 75) gives the triazaphosphole ( 176).277 Me

rn N, ,p

N-D

Me(,>N

N

R

(172) R = Me, Ph, or 2pyridyl

Me

Me (173)

( 174)

80 "C

Me (175)

(1 76)

The dibenzophosphole (177) has been prepared. It readily forms a range of quaternary salts (178), and a complex with nickel(1r) bromide. A comparison of the visible spectrum of the latter complex with that of the related complex of the acyclic ligand diphenyl(2-thieny1)phosphine indicates that the dibenzophosphole (177) appears to be a better donor towards the metal ion than the acyclic phosphine. The methyl and benzyl salts (178; R = Me or PhCH,, X = I or Br) undergo alkaline hydrolysis with preferential cleavage of the 2-thienyl group. The corresponding iodomethyl salt (178; R = CH21, X = I) undergoes hydrolysis to give a mixture of products, which include the ring-expanded system (179; R = H). A z7* C. Guimon, G. Pfister-Guillouzo, and F. Mathey, Nout.. J . Chim., 1979, 3 , 725 J . J . MacDougall, J . H. Nelson, F. Mathey, and J. J . Mayerle, Inorg. Chem., 1980, 19,

273

709.

274 275

276 277

J . H. Weinmaier, G . Brunnhuber, and A . Schrnidpeter, Chem. Ber., 1980, 113, 2278. J. H. Weinmaier, H. Tautz, A. Schmidpeter, and S. Pohl, J . Organomel. Chem., 1980, 185, 53. S. Pohl, Chem. Bcr., 1979, 112, 3159.

J-P. Majoral, R . Kraemer, T. N'Gando M'Pondo, and J . Navech, Tetrahedron Lett., 1980, 21, 1307.

Phosphiries arid Phosphorlium Sults

31

(178) R = Me, CHJ, or PhCH, X = Br or I

(177)

(179) R = H or CH,CO,Et

ring-expansion reaction also occurs in the reaction of the dibenzophosphole with ethyl propiolate in the presence of water to give (179; R=CHzC0,Et).278 Established ring-expansion and reduction reactions have been employed in a three-step synthesis of the dibenzo[b, d]phosphorin (1 80) from 5-bmzyldibenzop h o ~ p h o l e Mathey's .~~~ group has also shown that the phosphorin (181 ; R = Ph) forms two types of complex with cyclopentadienylmanganese systems, involving respectively, 0-co-ordination of phosphorus and z-co-ordination of the ring system to the Oxidation of (181 ;R = But) with various oxidizing agents has given both cationic and neutral radicals, containing two- and four-coordinate phosphorus, respectively.281 Full details have now appeared of the preparation and reactions of the diphosphabenzene (1 82). This compound seems to have some aromatic character, since it shows a strong absorbance in the U.V. at 282 nm. It is thermally stable, but air-sensitive, and it reacts with various acetylenic compounds to give diphosphabarrelene compounds (1 83) and with carbon tetrachloride to give (1 84).282 Photochemical and other cycloaddition reactions of the phosphabarrelenes (183) have given a number of new cage systems, e.g. (185), about which full details are now available.283

F3c0

F,C

RAR

(183) R = CF,, Me, or C0,Me

\

CF,

clYcl ( 184)

(185)

281

D. W . Allen and B. G. Hutley, Z . Narurfursch., Teil. B, 1979, 34, 1116. F. Nief, C. Charrier, F. Mathey, and M . Simalty, Tetrahedron Lett., 1980, 21, 1441. F. Nief, C. Charrier, F. Mathey, and M. Simalty, J . Organomet. Chem., 1980, 187, 277. K . Dimroth and W. Heide, Cofluq.Int. CNRS, 1977 (publ. 1978), 278, 151 (Chem. Absrr.,

282

Y. Kobayashi, H. Hamana, S. Fujino, A. Ohsawa, and I . Kumadaki. J . Am. Chern. Suc.,

383

Y. Kobayashi, H . Hamana, S. Fujino, A. Ohsawa, and 1. Kumadaki, J. Org. Chem., 1979,

278

279

280

1979, 91, 174 489). 1980, 102, 252.

44, 4930.

2

Quinquecovalent Phosphorus Compounds BY S . TRIPPETT

1 Introduction

The reactions and uses in organic synthesis of five-co-ordinatephosphoranes have been reviewed.' A new general synthesis of phosphoranes (1) has been described, involving the addition of PrI1species to activated olefins in the presence of an alcohol.2 The same reaction with dialkyl acetylenedicarboxylatesgives either the phosphoranes (2) or the ylides (3), which in some cases rearrange to give (2).3

R',P + A

x

+ R'OH

-

R',P + E C E C E + R'OH

I\/x

R',P,

R',PC(E)=CHE I

R ' ,P=C(E)CH

(OR ')E

(3)

2 Structure and Bonding X-Ray analysis has revealed geometry varying between trigonal-bipyramidal and square-pyramidal in the phosphoranes (4),4 (5),5 (6; X = 0),5 ( 6 ; X = S),6 (7),s (S),' (9),8 ( 1 1 ) , l o and (l2).loThe geometry of ( 5 ) is 93 % displaced along the .K. Burger in 'Organophosphorus Reagents in Organic Synthesis' ed. J . I . G . Cadogan, Academic Press, London, 1979. P. D. Beer, R. C. Edwards, C . D. Hall, J. R. Jennings, and R . J. Cozens, J . C ~ E I Soc., II. Chem. Commun., 1980, 351. 3 R. Burgada, Y. Leroux, and Y . 0. El Khoshnieh, Tetralrdron Left., 1980, 21, 925. 4 H. J. Bestmann, K. Roth, E. Wilhelm, R. Bohme, and H. Burzlaff, Angeit,. Cham., Int. I:(/. Engl., 1979, 18, 876. 5 R. 0. Day, A. C. Sau, and R. R. Holmes, J. Am. Chent. Soc., 1979, 101, 3791. 6 A. Schmidpeter, J. H. Weinmaier, W. S. Sheldrick, and D. Schornburg, 2. Naturfi)r.vc~h., Ted. B, 1979, 34,906. , W. S. Sheldrick, D. Schomburg, A . Schmidpeter, and T. v o n Criegern, Chern. Bcr., 1980, 113, 55. 8 D. Hellwinkel, W. Blaicher, W . Krapp, and W. S. Sheldrick, Cliem. Ber., 1980, 113, 1406. 9 H . W. Roesky, K. Ambrosius, M . Banek, and W. S. Sheldrick, Chem. Ber., 1980, 113, 1847. 10 D. Lux, W. Schwarz, H. Hess. and W. Zeiss, Z. Natirrforsch., Teil. B, 1980, 35, 269. . l

32

Quinquecovalent Phosphorus Cornpourids

33

C Yo

MeN’

C,F,-P

I

1 ,I&,H,CF,m 1 ‘Nc,H,cF,-~

MeN,.

1

C O\

M e P o O\L--NSiMe, Me2”/ N-PNMe, Me, Si

I

Berry co-ordinate to square-pyramidal. In both ( 1 1) and (12) the dimethylaminogroups are cis with respect to the four-membered rings. The compound originally thought to be the first phosphorane with five P-N bonds has now been shown by X-ray analysis to be the betaine (13).11 11

M . Halstenberg, R . Appei, G . Huttner, and J. U. Seyerl, Z . Nafurforsth., Teil.B, 1979, 34, 1491.

34

Organophosphorus Chemistrj*

'

0,P -NSiMe / 1 \,NMe, N-P M e , &,0'1

O d M e

3 Hydroxyphosphoranes

The hydroxyphosphorane (14), previously obtained as a crystalline 1 : 1 complex with TFAA, has now been obtained crystalline in its own right.12 It is O-methylated by diazomethane and stable in methanol or ethanol, although decomposed by water. With methylmagnesium iodide it gives the phosphorane (1 5). Details have appeared of the synthesis and reactions of the hydroxyphosphoranes (16) and (17).l:%Whereas (16) does not react with diazomethane, and is estimated to have pKa of 10-1 I , ( 17) gives a crystalline five-co-ordinate salt o n treatment with aqueous NaOH, and is shown by titration to have pKa of 5.3 k0.2.

MeMgI

0 (14)

(15)

F,C

(17)

CF,

High-field 31Pn.m.r. signals that were observed in the reactions of the phosphonate anion (18) with nitrones have been interpreted in terms of phosphoranoxide anion intermediates such as (19).14 12 l3

l4

Y . Segall and 1. Granoth, J . Am. C ' h ~ t nSo(.., . 1979, 101, 3687. I . Granoth and J . C. Martin, J . A m . Chctn. So(,., 1979, 101, 4618. S. Zbaida and E. Breuer, Exprricwfiu, 1979, 35, R 5 1 .

35

QuinquecovalentPhosphorus Compounds

CN

x>p P R '

'

0 (41)

7 Five-membered Phosphoranes Diethyl azodicarboxylate condenses with cyclic PII1 compounds (44) to give spirophosphoranes (49, which rapidly exchange with 1,Zdiols or 2-amino28 28

I. S. Segal and F. H. Westheimer, J. Am. Chem. Suc., 1979, 101, 5329, 5334.

S. A. Terent'eva, M. A. Pudovik, and A. N. Pudovik, Izv. Akad. Nauk SSSR,

Sw. Khim.,

1979, 1150 (Chem. Absrr., 1979, 91, 91 712). H. 9. Stegmann, H. V. Dumm, A. Burmester, and K. Scheffler, Phosphorus Sulfur, 1980,8, 59.

Quinquecovalent Phosphorus Compounds

39

NCO Et

NCO Et (44)

(45 )

(R’= F, CI, OCH(CF,),, Me,or But] [R’=F,CI,or OCH(CF,)?]

(46)

R’ (47) R, = CF,

alcohols to give (46).311,l,1-Trifluoroacetone reacts with P I I I compounds to give initially 1,3,4-dioxaphospholans, which rearrange on warming to give the 1,3,2d i o x a p h o s p h ~ l a n s 2: .~~ 1 Adducts (47) have been obtained from hexafluoroacetone and a range of (t-butyl)phosphines, and their variable-temperature n.m.r. spectra have been investigated. 33 Treatment of the (trimethylsily1oxy)phosphorane (48) with water or hydrogen chloride gave the phosphinate (49), whose structure was confirmed by X-ray ~rystallography.~~ In some of its reactions (see Scheme 2), (49) behaves as the corresponding hydroxyphosphorane. RF

...

0’ I OSiMe, (48)

(49)

RF = CF,

c1 Reagents: i, HzO or HCI; ii, MesSiCI, EtsN; iii, SOC12; iv, (49) f EtsN

Scheme 2 J-P. Majoral, R. Kraemer, T. N’gando M’pondo, and J . Navech, Tetrahedron Lett., 1980, 21, 1307; H . Goncalves, J. R . Dormoy, Y. Chapleur, B. Castro, H . Fauduet, and R . Burgada, Phosphorus SulJur, 1980, 8 , 147; J . Navech, R. Kraemer, and J-P. Majoral, Tetrahedron Lett., 1980, 21, 1449. A. M . Kibardin, T. Kh. Gazizov, P. I . Gryaznov, and A. N. Pudovik, Zzo. Akad. Nnuk SSSR, Ser. Khim., 1979, 1 39 1. D. Dakternieks, G . V. Roschenthaler, K. Sauerbrey, and R . Schmutzler, Chem. BET., 1979, 112, 2380. D. Schomburg, 0. Stelzer, N . Weferling, R. Schmutzler, and W. S . Sheldrick, Chem. Ber., 1980, 113, 1566.

40

Organophosphorus Chrmistrj.

CN

Br

(52) R = Me, Et, OAc, SiMe,, or

Variable-temperature n.m.r. data on the phosphoranes (50) and (51; X = C1, CN, N3, NCO, or NCS) suggest an order of relative apicophilicity of CN> C l x NCO x NCS > N, > OPh.35Treatment of a range of phosphites (52) with bromine gave the bromophosphorane (53).36 The cyclic phosphazenes (54) and (57) have now been added to nitrile oxides, epoxides, a-halogeno-ketones, nitrileimines, or nitrones to give bicyclic phosA phoranes such as ( 5 5 ) and (56), some of which have great thermal ~tability.~’ synthesis of 1-azirines from a-bromo-ketoximes oiu the phosphoranes (58) is outlined in Scheme 3.38

K;/~phl

+ -. R’CNO

I

/

C0,Me

I

Me0,C

\

Me2P’ar2

I

R’,P-N

I

(57) X = CN o r C0,Et

(56) 35

36 3i

3H

J . Brierley, J . I . Dickstein, and S. Trippett. Phosphurus SulJirr, 1979, 7, 167. J . G l o e d e and H . Gross, Z . Anorg. A&. Chem., 1979, 458, 108; Phosphorus Sulfur, 1979, 7 , 57. A. Schmidpeter and T. von Criegern, Chem. Bey., 1979, 112, 2762, 3472. A . Hassner and V . Alexanian, J . Org. Chrni.,1979, 44, 3861.

Quinquecoualent Phosphorus Compounds RC(=NOH)CH,Br

41

//NOCMe2oMe

-& RC

\

//NOCMezoMe Br \ + CH,PPh,

-IF, RC

CH,Br

Reagents: i, MezC(OMe)z, H + ;i i , Ph3P; iii, H20,H + ; iv, Et3N; v, 120 "C

Scheme 3

A further account has appeared of the reactions of phosphites with l-bromo-ln i t r o a l k e n e ~Among .~~ other phosphoranes described are (59),40(60),4 and (61) and its trans-is~rner;~~ (61) and its isomer are formed stereospecifically from the cis- and rruns-2H-ly2,3-diazaphospholes. Ph

PhN-

3Y 40 41

42

C(COPh), + (MeO),P

---+

COPh

i7 O,p,Nph

R . D. Gareev, G . M . Loginova, I. N. Zykov, and A. N. Pudovik, J . Gen Chem. U S S R (Eng/. Transl.), 1979, 49, 20. N . A . Polezhaeva, M. N. Agafonov, and B. A. Arbuzov, In.Akad. Nuuk SSSR, Ser. Khim., 1979, 608 (Chem. Abstr., 1979, 91, 56 548). Yu. V. Balitskii and Yu. G . Gololobov, J . Gen. Chem. U S S R (Engl. Transl.), 1978,48,2532. G . Baccolini, P. Spagnolo, and P. 0. Todesco, Phosphorus Sulfur, 1980, 8, 127.

42


(6 2)

The hydrolyses of the phosphoranes (62) in D M F or dioxan are second-order in water, whereas in ethanol they are first-order in water.43

8 Six-membered Phosphoranes The cyclic anhydride (63), derived from salicylic acid, has been added to a-ketoacids and to ,!%propiolactoneor acrylic acid as shown in Scheme 4, to give the phosphoranes (65) and (M), re~pectively.~~

aco2H q r + PhPCI,

\

OH

0

(65)

(64) Reagents: i , EtsN; ii, RCOC02H; iii, H2C=CHC02H or

Scheme 4 9 Six-co-ordinate Species

The equilibria between the five-co-ordinate (66) and six-co-ordinate (67) species have been investigated and a number of the latter The chlorophosphorane (68) reacts with the bipyridyl (69) to give the six-co-ordinate salt (70).**

(67) 43

V. A. Belskii, L. A. Khismatullina, T. G . Bykova, A. V. Burykina, and B. E. I v a n o v , J . Gen.

44

S. Kobayashi, T. Kobayashi, and T.Saegusa,

Chem. USSR (Engl. Transl.), 1979, 49, 298.

45

46

Chem. Lett., 1979, 393. C. Bui Cong, G. Gence, B. Garrigues, M. Koenig, a n d A. Munoz, Tetrahedron. 1979, 35, 1825. T. von Criegern and A. Schmidpeter, Phosphorus Sulfur, 1979, 7 , 305.

Quinquecovalent Phosphorus Compounds

43

Cl

(7 1) R = 13, Ph,or C,H,N

(72)

(74)

With the pyridyl ketones (71), (68) gives salts (72), which, with trimethyl phosphite, undergo Arbuzov reactions t o give the neutral species (73).46 These exist as diastereoisomers, which interconvert with a free-energy barrier of 18 kcal mol-I. With pentane-2,4-dione in the presence of triethylamine, (68) forms the neutral complex (74).45

-

+ Me,SiCl

Six-co-ordinate intermediates, such as ( 7 9 , in the substitution reactions of chlorophosphoranes with trimethylsilyl azide or benzyltributylammonium azide .~~ of have been detected at low temperatures by 31Pn.m.r. s p e c t r o s ~ o p y Attack 47

A. Skowronska, M . Pakulski, and J. Michalski, J . Am. Chem, SOC.,1979, 101, 7412.

44

+ P 4 + Et,N

--+

[

But

But \

Et,NH 0

+ P, + (79) + 5 :0.5: 1 (81)

nucleophiles on tetraoxyspirophosphoranes such as (76; X = F or OC,H,F-p) is kinetically c o n t r ~ l l e dAt . ~ ~low temperatures the thermodynamically less stable trans-anions (77) are formed; on warming, these isomerize to the stable cisisomers (78). This effect has been ascribed to stereoelectronic control from the p-type lone-pairs on the four cyclic oxygen atoms. The salt (80) was obtained as a mixture of isomers on treating the quinone (79) with white phosphorus and triethylamine in molar ratios of 1 :0.25:2, the ratio of isomers depending o n the conditions during the addition of the a m i r ~ eOnly .~~ one isomer of (80) was formed o n treating the phosphorane (81) with triethylamine.

48 49

J. J . H. M . Font Freide and S. Trippett, J . Chenr. Soc., Chem. Commun., 1980, 157. M . I . Kabachnik, D. 1. Lobanov, and P. V. Petrovskii. Izu. Akud. Nuuk SSSR, Ser. Khim. 1979, 2398 (Chent. Abstr., 1980, 92, 76 421).

J

Halogenophosphines and Related Compounds BY J. A. MILLER

1 Introduction

This year’s literature has seen steady development of existing trends. Thus the phosphorus iodides are now being more thoroughly investigated, and the potential of these phosphorus(ir1) derivatives in deoxygenation and related synthetic reactions is beginning to be realized. It is also becoming clear that phosphaalkenes are here to stay, and that this bond has alkene rather than ylide properties. Silylphosphine chemistry is proving more popular, notably in the field of multiple-bond insertion reactions. 2 Halogenophosphines

Preparation.-The conversion of diphenyl ether into 10-chlorophenoxarsine (1 ) is a much-patented reaction, and a very detailed study of possible combinations of reagents and synthetic conditions has been reported.’ Scheme 1 outlines two of the most efficient systems, which lead to (1) in SOY/, yield.

Don \

/

1

I

c1

U

(1) Reagents: i. AsCls. AICIs.

H3P04; i i , A s 2 0 3 ,

AlCls

Scheme 1

Halogen-displacement reactions, using metal iodides, continue to be used for the preparation of iodophosphines,2p as for (2) and (3). Trimethylsilyl isothiocyanate (4) has been used to prepare isocyanatoph~sphines.~ Alkyl(dich1oro)A . B. Yaroshevskii, V. N . Khlcbnikov, V. I . Gavrilov, and B. D. Chernokal’skji, J . Gpn. C ’ l i c n i . U S S R (ErrgI. Trcrnsl.). 1979, 49, 717. E . A . Mcl’nichuk and N . G. Feshchenko, J . Gcn. Clicni. USSR ( E n g l . Trcrnsl.), 1979, 49,

1457. M . M . Kahachnik, A. A . Prishchenko, Z . S. Novikova, and I . F. Lutsenko. J . Gcn. Clic>ni. ( J S S K (Etigl. Trtirisl.). 1979, 49, 1264. A. N . I’udovik, G . V. Romanov, and T. Ya. Stepanova. J . Gcn. Chrrn. U S S R (Engl. Trarisl.), 1979, 49, 1248.

45

46

Orgctnophosphorrrs Chrrnistr.1)

100 150°C

R,_,PCl, + n Me,SiN=C=-S (4)

R'P(NR',), (5)

R' N H . H C I

n Me,SiCl+ R,-,P(N=C=s),

R'P(NR',)Cl

R 1,NH . HCI __x___)

R*PCI,

phosphines are not accessible by exchange from phosphondiamidites ( 5 ) , 5 as shown. Physical and Structural Properties.-Electron-diffraction studies of the fluorophosphines (6)'j and (7)7 have been reported. The latter is planar in the gas phase, and has C3,r~ymrnetry.~ MNDO SCF molecular orbital calculations8 on the related phosphines ( 8 ) and (9) give good predictions for geometry, conformation (notably lone-pair relationships), and rotational barriers. He( I ) photoelectron spectroscopy has been used to study the pyrolysis of dichloro(ethy1)phosphine ( and to maximize the yield of phosphapropyne ( I I). A range of ethylphosphines (12) have been investigated by multinuclear n.m.r.'O

-

(7)

EtPCl,

heat

k' ,PNR

RP(F)NMe,

(8) R = H or Me

(9) R = Me or Ph

MeCEP

Et,PX,_,

(11)

(12)n=0-3 X = I, Br, or C1

Descriptions of electron-diffraction studies on chloromethyl(dich1oro)phosphine and on 2-thienyl(dichloro)phosphine ( 1 4 y have appeared, and the latter phosphine, together with related aryl(dich1oro)phosphines ( 1 5), has also been studied using the Kerr effect.':'

( 13)"

5 6

7 8 9

10 11 12

13

N . A . Andreev and 0. N . Grishina, J . G'ott. C ' l w t i t . U S S R (Etigl. Trutisl.), 1979, 49, 623. G . S. Laurenson and D. W . Rankin, J . :21o1. Strtict., 1979, 54, 11 1. D. E. J . Arnold, D. W. H. Rankin, M . R . Todd, and R. Scip, J . Chrm. S o c . , Dultotr Trurts., 1979, 1290. W. B. Jennings, J. H. Hargis, and S. D . Worley, J . Clrc~m.Soc., Clirnr. Comtriun., 1980, 3 0 . N. P. C. Westwood, H . W. Kroto, J . F. Niuon, and N. P. C. Simmons, J . Chem. Soc., Dalton Trans., 1979, 1405. J . P. Van Linthoudt, E. P. Van Den Berghe, and G. P. Van Der Kelen, Spcctrochiiii. Actrr, Part A , 1979, 35, 1307. L. L. Tuzova and V. A. Naumov, Z h . Sfruht, Klrim., 1979, 20, 923. S. A . Shaidulin and V. A . Naumov, Zh. Srruhr. Khinl., 1979, 20. 728. R. P. Arshinova and S. G . Vul'fson. Zlr. Struhf. K f i i m . , 1979, 20, 862.

Halugenophosphines and Related Compound.$

47

C1,PR

( 1 5 ) R = Ar

(16) X = Br or I

(17)n=O,l,or2

Octahedral five-co-ordiriated structures (1 6) have been found for the dimeric adducts of sodium salts of crown ethers and tricyanophosphine.'l The nickel(o) complexes of general formula ( 1 7 p of which (17; t i = 2) is the most stable, do not show the same stability order as do the corresponding borane complexes. Reactions with Alkenes or A1kynes.-It is now the turn of bromophosphines to have their reactivity towards carbon-carbon multiple bonds investigated. Thus phosphorus tribromide adds to phenylethyne,16and to hex-1-yne," in the presence of oxygen. The dominant products, shown in Scheme 2, arise via trans-addition,

Reagent5: i, P h C = C H ,

0 2 ,

at 20 " C ; ii, H C r C B u ,

0 2

Scheme 2

and a previous rationalization,In ria a cyclic transition state, has now been revised. l7 A radical mechanism has now been proposed to account for the requirement for oxygen and for the regiochemistry.16 The corresponding reactions of phosphorus tribromide with 1-alkynyl ethers or enol etherslg and with ketenZodo not require oxygen. This, and the regiochemistry (apparent from Scheme 3), indicate that a different pathway is being followed, and is likely to be an ionic one for the ethers. These reaction products are all vinylphosphonous dihalides, and their conversion into phosphoranes by phosphorus pentachloride"? 2 2 is discussed in Section 4 of this chapter. 1.1

1s 16

17 18

19 20

"1 22

W. S. Sheldrick, F. Zwaschka, and A. Schmidpeter, Angctt.. Chcm., Int. Ed. EngI.. 1979, 18, 935. D. C . Staplin and R . W. Parry, Inorg. Chctn., 1979, 18, 1473; R . G . Montemayor and R. W. Parry, ihirl., p. 1470. A . S. Kruglov, E. L. Oskotskii, A . V. Dogadina, B. I . lonin, and A. A. Petrov, J . (;en. Cliern. U S S R (Engl. Transl.), 1978, 48, 137 1 . S. V. Fridland and R . M . Fatkhullin, J . Gcn. Cliem. U S S R (EngI. Transl.), 1979, 49, 417. S. V. Fridland, T. M. Shchukareva, and R . A . Salakhutdinov, J . Grn. Cltcni. U S S R (Engl. Trcrnsl.), 1976, 46, 1213. M . A. Kazankova, I . G . Trostyanskaya, A . R. Kudinov. and I . F. Lutsenko, J . Grn. Chrrn. U S S R (EngI. Transl.), 1979, 49, 41 I . M . A . Kazankova, A. R . Kudinov, and 1. F. Lutsenko, J . Grn. Chcm. U S S R (Engl. Transl.), 1979, 49, 414. S. V. Fridland and A. I . Efremov. J . Gen. Chrm. U S S R ( E n g l . Transl.), 1979, 49. 8 2 . S. V. Fridland, A. I . Efremov, Yu. K . Malkov, and Sh. S. Bikeev, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 663.

48

Orgurrophosphorus Chemistrjl

PBr ,

+

RC

COMe

- Br2pxoMe PBr,

+

HBI

BuOCH =CH

Br

R

-

Br,P

__+

H

OBu

0

+ PX,

H,C=C=O

bx

II

( X = Brl

Br,PCH,CBr

+

= C''

no reaction

Scheme 3

Further reactions of 1,3-dienes with phosphorus(rr1) halides have been applied to the synthesis of isophosphindoline precursors,23 as shown in Scheme 4. Standard displacement of halogen from phosphorus by malonate-derived enolate anions leads to the phosphines ( 18),24and these have subsequently been reported 25 to be in equilibrium with ylides; see ref. 26 for another example, and Chapter 10 for details.

Reagents: i, (Me2N)sP [88% yield]; ii, LiAIH4 [50% yield]

yield]; iii, H z 0 2 [50% yield], iv, heat

Scheme 4

R,PC1 + CH,(CO,Me),

Et,N

H R,PCH(CO,Me),

==+

R,P=C(CO,Me),

(18)

Reactions with Amines and Derivatives.-The course of the reactions between dichlorophosphines and derivatives of urea is wholly dependent upon the remaining ligand at p h o s p h ~ r u s as ,~~ shown in Scheme 5 . In each of the cases described, the initial product readily rearranges. 23 2.1

25 26

27

E. D. Middlemas and L. D. Quin, J . O r g . C/w/?i.,1979, 44, 2587. 0. I . Kolodyazhnyr, J . G m . Chcni. U S S R (EngI. Trcmd.), 1979, 49, 88. 0. I . Kolodyazhnyi, Tcrrcrhcdron L r t f . , 1980, 21, 2269. T. A . Mastryukova, I . M . Aladzheva, 1. V . Leont'cva, P. V. Petrovski, E. I . Fediii, and M. I . Kabachnik, Tc.rraltetlron Lcrt., 1980, 21, 2931. H . W . Roesky, K . Ambrosius, M . Banek, and W. S. Sheldrick, Cfic.m. B u . . 1980, 113, 1847.

Hnloffetiophosphines arid Relutrd Compoimds

49

R'PCI, + (Me,SiNR2),C0

I'

I R ' = C , I-',I R

0

22

= Me and -

-

ArN-

NMe

l o 1

2PC1,

P'

P'

I

MeN

I

N Ar

Y 0

Scheme 5

Some less spectacular reactions 28-30 of chlorophosphines with amines are presented in Scheme 6. 0

II

MePCl, + ButCCH2NHBut

-

MePBut But

ref. 28

N

[ 7 w CI,PCH,PCI, + 2Et,NH

Ar'PCl, + Ar'NH,

-

2R,N

fi

(Et,NP(CI)],CH,

ref. 29

[SSrO]

Ar'P(C1)NHAr' + Ar'P(NHAr'),

ref. 30

Scheme 6

29

Yu. V. Balitskii, L. F. Kasukhin, M . P. Ponomarchuk, and Yu. G . Gololobov, J . Gen. C h ~ n iU . S S R (Engl. Trunsl.), 1979, 49, 34. Z . S . Novikova, A. A. Prishchenko, and I . F. Lutsenko. J . G m . Chpm. USSR (Engl. Trunsl.),

30

Yu. G . Trishin, V. N . Chistokletov, and A. A . Petrov, J . Cen. Clicm. U S S R (Engl. Transl.),

28

1979, 49, 616. 1979. 49. 39.

50

Organophosphorus Chcmisrr.r,

Reactions with Carbonyl Compounds.-This has been an active area this year, although most of the work has essentially confirmed established patterns of reactivity. Nevertheless some interesting new points have emerged, notably from a detailed study of the reactions of simple aliphatic aldehydes with phosphorus trichloride and with various other chlorophosphines; see Scheme 7 for the 0

II

C1, PCHMeOCH(C1)Me [ 34%]

0

0

I1

II

Cl,PCHPrOCH(Cl)Pr + Cl,PCHPrOCH=CHEt [ 16%] [36%1

I

R1,PCl + R T H O

Ph

\ II

PCHPrOCH-CHEt

c1’

[ 34%J

0

I1

Et I PCHPrOCH =CHEt (65%] Scheme 7

C1 PhPC1, + PrCHO

I

F===Ph-P--OCHPr

*

I

c1

Cl

c1

0

\!CHPdHPr Ph’

c1 t-

I

c1

I

PhPOCHPrOCHPr

( 19)

Scheme 8

51

Halogenophosphines und Related Compound.s

products that were isolated after quenching with phosphorus pentachloride. A unified pathway has been proposed for these reactions,31 largely on the basis of a 31Pn.m.r. study of the reactions of dichloro(phenyl)phosphine, and on the basis of the product structures and reaction stoicheiometry. The author’s interpretation (Scheme 8) envisages an electrophilic role for the phosphines, and suggests an Arbusov-type isomerization as the key step leading to the oxides (19) and (20). Perhaps the main weakness of the scheme is that the formation of bis(a-chloroalkyl) ethers (21) is ascribed to the reaction of phosphorus pentachloride with 0

II

[R’=R’=H)

ArP(C1)CH I CI 173%)

0

I

0

[ 45%]

0-p-0

I

dPh*fJ Ph

Ph

OH

(25 1

Ph

CI

+

Ph I

(26) 31

S. Kh. Nurtdinov, V. I . Savran, T. V. Zykova, R . A . Salakhutdinov, and V. S. Tsivunin, J . G m . Chent. USSR (Engf. Trans/.), 1979, 49, 2159.

52

Organophosphorus Chrmi.str.i*

(20), although it seems likely, in view of earlier that these ethers are produced at the outset of the sequence, i.e. before the pentahalide has been added. Related reactions of dichloro(p-fluoropheny1)phosphine (22) have also been When the ketone (23) is treated with phosphorus trichloride and acetic acid, the a-chloro-ether (24) is formed rapidly, but it subsequently reacts to form the acids (25) and (26).34 Dicarbonyl compounds react with halogenophosphines in a reductive fashion, illustrated in Scheme 9 for chlorodiethylphosphine. 35 A more unusual sequence occurs when acetylacetone reacts with dichloro(phenyl)phosphine which has been previously complexed ;36 see Scheme 10. 0

It Et,PCI + MeCR

0

-+

0

I/

I1 Et,PC(CI)R

--+ Et,PCHR

I

I

Me

Me

(R = CH,COMe, CH,CO,Et, or COMe) Scheme 9

1

c1

PhP(CI),.Cr(CO), + MeCOCH,COMe

I 5 PhP.Cr(CO), --+

PhP

0

Scheme 10

-

Reactions with Acetals and Alcohols.-The reaction of chlorodiphenylphosphine with N-methoxymethyl-amines leads to the oxide (27),37and to an improved route to (28).38The acylals (29) have been converted into the esters (30).39*40 These reactions all seem to involve nucleophilic attack by an ether oxygen o n the

“i’“

Ph,PCH,NPh

- -

( 2 7 ) [ 89%I

Me

I

MeOCH,NPh

MeOC H “ 7 0 ~

Ph,PCI

0

11

Ph,PCH,N

no W

(28)

J. A . Miller and M . J . Nunn, J. Chcni. Soc., PrrXin Truns. I , 1976, 5 3 5 . s3 F. V. Bagrov, L. A . Vasil‘eva. Yu. P. Stifanova, and 0. S. Kuznetsova, J. G‘4.n. C h ~ r i i .U S S R (Engl. Trunsl.), 1979, 49, 1089. 34 V. I . Vysotskii, I . A. Vasil’eva, V. N . Chcrnii, K. Ci. Chuprakova, and M . N. Tilichenko. J. Gcn. Chi>t)i.U S S R (Engl. Transl.). 1979, 49, 1714. 3 5 S. Kh. Nurtdinov, I . M . Kashirskaya, N . M . Isniagilova, T. V. Zykova, K. A . Salakhuidinov, and V. S. Tsivunin. J. Giw. Chcm. U S S R (Engl. Trans!.), 1979, 49, 85. 3(; J. von Seyerl, D. Neugebauer, and Ci. Huttner, Chrni. Bcr., 1979, 112, 3637. 3 i N. L. J. M. Broekhof, F. L. Jonkers, and A. van der Gen, Tetrahc~clrorr L c t f . , I980,21, 7671. 3 H N. L. J. M . Broekhof, F. L. Jonkers, arid A. van der Gen, Tctrolicdron L c t t . , 1979, 1433. 3 9 M. B. Gazizov, J. Gcn. Chem. U S S R (Engl. Triinsl.), 1978, 48, 1477. M. B. Gazizov, J. Gcn. Chc>m.U S S R (Engl. Trrinsl.), 1979, 49, 322. 32

Halogenophosphines and Related Compounds

OEt

0

I I1 MeCHOCH,CR' + R'PCl,

,

R 'P( OCH COR ' )

+

__f

OEt

(29)

I

Arbusov

53 0

11 I

R2P--OCH,COR'

MeCHOEt (30) [60-90%]

MeCHCl

chlorophosphine, and the reactions of (29) are unusual in that (30) appears to be derived from a highly selective interaction with only one of the acetal oxygens in (29). Addition of an alcohol to difluoro(pheny1)phosphine at a low temperature produces phosphoranes, which, at room temperature, lose hydrogen fluoride to yield phosphonofluoridites;41 see Scheme 11.

- I:

PhPF,+ROH

(

PH, + ( H , S i ) , N

_____+

Scheme 19

4 Halogenophosphoranes Preparation.-A surprising and efficient reaction of tri-n-butylphosphine with perfluoroalkenes leads to fluorophosphoranes, e.g. (46),'* the geometry of which is 90-100% (2).An interesting feature of the reaction is that it requires that two fluorines be attached to the carbon under attack, i.e. it is specific for the terminal unit C=CF2. The fluorophosphorane (47) is one of a number of fluxional phosphoranes that have been prepared7I by a range of novel routes; see Chapter 2 for details. Addition reactions of fluorophosphines have been used to prepare the phosphoranes (48)72and (49)," for which full n.m.r. and other data are provided. The iodophosphoranes (50)73and (51)5s have been prepared as shown.

F3cw F

CF,CF=CF,

+ Bun 3 P ---+

I:

/

\

PBu",

I

F (46) 63 64

65

66 87 68 69

70

71 72

73

R. Appel, V. Barth, M. Halstenberg, G . Huttner, and J . von Seyer, Angew. Chem., Int. Ed. Engl., 1979, 18, 872. R. Appel, V. Barth, F. Knoll, and I . Ruppert, Angew. Chem., Int. Ed. Engl., 1979,18, 873. R. Appel and 33. Laubach, Tetrahedron Left., 1980, 21, 2497. R. Appel and V. Barth, Tetrahedron Left., 1980, 21, 1923. R. Appel and V. Barth, Angew. Chem., Int. Ed. Engl., 1979, 18, 469. G. Fritz and H. 0. Berkenhoff, 2. Anorg. Allg. Chem., 1957, 289, 250. A. D. Norman and W. L. Jolly, fnorg. Chem., 1979, 18, 1594. D. J. Burton, S. Shinya, and R. D. Howells, J . Am. Chem. Soc., 1979, 101, 3689. H. Schmidbaur and P. Holl, Z . Anorg. Allg. Chem., 1979, 458, 249. L. I. Nesterova and Yu. G. Gololobov, J . Gen. Chem. USSR (EngI. Trans/.).1979, 49. 2329. V. D. Romanenko, V. I . Tovstenko, and L. N . Markovskii, J . Cen. Chem. USSR (Engl. Transl.), 1979, 49, 1680.


59 €

(47) [ l o o % ]

X,PN(Me)CH,CO,R + PhN,

-

(X = F, OMe, or NMe,)

PhPF,+ROH

I X = F\

X,PN(Me)CH,CO,R

I.-

-

Ph!,

I

P-NMe

I:‘ I

(
OR

NPh 11

N

10°C)

7

I

I

F

F

Ph-P

I/ H I ‘OR

F

Me ,Sil + R,P--O

-

(49)

OSiMe,

I I

R,P I

(50)

Physical and Structural Aspects.-A considerable amount of effort continues to be invested in structural studies of phosphorus pentachloride. Although not strictly ‘organophosphorus’ chemistry, these studies are nevertheless relevant to our topic, and may in time aid advances in the understanding of the chemistry of phosphorus pentachloride. For example, a detailed Russian paper ’* reveals some quantitative data, based on U.V. studies, on the degree and nature of the dissociation of phosphorus pentachloride, in a range of solvents. The equilibria in question are shown in Scheme 20, and are dependent upon the dielectric constant of the medium, and on the concentration of the solute. Pa,

PCI,

=

2PC1,

favoured by high concentration, and by media with high dielectric constant

*

zia, 2c1favoured at low concentration

Scheme 20 L. M . Sergienko, G . V. Ratovskii, A. M . Dodonov, and A. V. Kalabina, J . Grn. Chrm. USSR (Engl. Transl.), 1979, 49, 1743.

60

Organophosphorus Chc.mistry

Other papers have concentrated on the species present in solid phosphorus penta~hloride,~~ and how these relate to the solvent used to crystallize it, and on the pressure to which it is e x p o ~ e d . ~ ~ - ~ ~ Studies of the U.V.spectrum of phenyltetrachlorophosphorane (52) show that it is molecular in all the solvents investigated, whilst its relative (53) is ionic in dichloromethane and in a ~ e t o n i t r i l e .Conductivity ~~ data indicate that the halogenoarsoranes (54) are predominantly molecular in solution.80 Phenyltetrafluorophosphorane ( 5 5 ) has been studied by electron diffraction,a1 and intramolecular exchange in phenyltrifluorophosphorane (56) has been studied by dynamic n.m.r. spectroscopy; a value for AG*2g8of 13.3 kcal mol-l was found for the exchange barrier.B2 PhPX,

Ph,PCI,

R,AsX,

PhPHF,

(52) X = C1 (55) x = F

(53)

(54) R = Ph or Et

(56)

Reactions of Ha1ogenophosphoranes.-One has come to expect the annual batch of reactions of phosphorus pentachloride with simple (usually monofunctional) organic compounds. This year is no exception, although hardly any of the reported reactions is achieved cleanly - a perpetual problem in this field - and reaction pathways are rarely 2 2 * 8 3 - 8 7 Scheme 21 gives a selection of this year's goodies! Evidence for the formation of molecular complexes between phosphorus pentachloride and enol ethersa8or d i e n e ~has ~ ~appeared. - ~ ~ A detailed study of the reaction of trimethysilyl azide with catechol-based phosphoranes has been published.90At low temperatures, a series of stoicheiometry-dependent Pv-Pvr equilibria are observed (by n.m.r.); see Scheme 22. Simple substitution reactions of phosphorus pentaiodide have been des~ribed,~' 75 76

77 78 79 80

81 82

83 84 85

E6

87 88 89 90 91

A. Finch, P. N. Gates, H . D . B. Jenkins, and K. P. Thakur, J . Chem. SOC., Chem. Commun., 1980, 579. R. Cahay and E. Walley, J . Chem. Phys., 1979, 70, 5534. R. Cahay, P. T. T. Wong, and E. Walley, J . Chem. Phys., 1979, 70, 5539. J. A. Ripmeister, P. T. T. Wong, D . W. Davidson, and E. Walley, J . Chem. Phys., 1979,70,

5545. L. M. Sergienko, G. V. Ratovskii, V. I . Dmitriev, and B. V. Timokhin, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 275. B. E. Abalonin, I. I . Kosolapova, L. A. Lokhotskaya, and Z. M. Izmailova, J . Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 332. C . Dittebrandt and H. Oberhammer, J . Mol. Srrucr., 1980, 63, 227. R. K. Marat and A. F. Janzen, Inorg. Chem., 1980, 19, 798. V. E. Kolbina, V. G . Rozinov, and V. I . Glukhikh, J . Gen. Chem. U S S R (Engl. Transl.), 1978,48, 2534. V. E. Kolbina, V. G . Rozinov, V. I. Glukhikh, and G. V. Ratovskii. J . Gen. Chem. USSR (Engl. Transl.), 1978, 48, 2535. G . A. Pensionerova, V. G. Rozinov, and V. I . Glukhikh, J . Gen. Chem. U S S R (Engl. Transl.), 1978,48, 2536. V. G . Rozinov and V. E. Kolbina, J . Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 1456. V. V. Kormachev, Yu. N. Mitrasov, and V. A . Kukhtin, J. Gen. Chem. USSR (Engl. Transl.), 1979, 49, 1249. S . V. Fridland, A . 1. Efremov, and B. D. Chernokal'skii, J . Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 873. S . V. Fridland, V. S. Minkin, A. I. Efremov, E. S. Nefed'ev, and B. D. Chernokal'skii, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 876. A. Skowronska, M. Pakulski, and J . Michalski, J . Am. Chem. Soc., 1979, 101, 7412. V. G . Kostina and N. G . Feshchenko, J . Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 2165.


61

0 PhCH =CHPCI,

"L,,

L11

ref. 83

[ 24701

PCl,

vi. iii ref, 85

/o

II

RN( Et)CH=C(Cl)PCl,

-

ROCH-CHPCl,

\

[95%]

ref. 86

0 RC(C1) =CHPCl,

I1

[ 30- 35%]

[~OCTI

Reagents: i, PhCH=CHPCIz; ii, ROCHzCH=CHz; RCOMe; vi, RNEtz; vii, MeCOEt

Scheme 21

i i i , SOz; iv, ROCH=CHPC12; v,

c1

N=N==NSiMe

Scheme 22 PhOPI, it

I(CH2),I [ 93%]

2 PI,

(PhNH),PI, + some (PhNH),PI

ul

R,PI, [ R = Ph, 88%] Reagents: i, 1 molar equivalent o f PhOH, at 5 " C ;i i , 6 molar equivalents of PhNHz; iii, R3PO; iv, tetrahydrofuran

Scheme 23

and are illustrated in Scheme 23. Reactions of phosphorus pentachloride with 2,4,6-tribromophenol 9 2 and with t-butyl-lithium have been reported.a3 82

E. S. Kozlov, N . P. Kolesnik, L. G . Dubenko, and M. I . Povolotskii, J. Gen. Chem. U S S R

(Etigl. Transl.), 1979, 49, 666. 93

V. I . Drnitriev and B. V. Timokhin, J . G6.n. Chcm. U S S R (Engl. Transl.), 1978. 48, 1405.

3*

62

Organophosphorus Chernistrj,

Reactions of Halogenophosphoranes Relevant to Organic Synthesis.-A review is devoted to the uses of antimony pentahalides SbX5 (X = F or CI) as FriedelCrafts or oxidation catalysts.g4 The virtues of mixtures of phosphorus pentachloride and peroxide as CIchlorinating agents for simple alkylbenzenes have been described.R5Conversion of trimethylsilyl ethers and phosphorus(1v) esters into the corresponding chlorides has been r e p ~ r t e d , as ~ ~shown - ~ ~ in Scheme 24, and in the phosphonate series it is particularly efficient. Some of the structural limitations of these reactions have been 0

II (Me,SiOCH,),POSiMe,

P These studies of flavodoxin are an indication of the renewed interest in phosphorus-containing coenzymes which has been apparent in the past year. Not only have thiamine and pyridoxal phosphates been the subjects of a recent volume of ‘Methods in but also the use of immobilized nucleotides and coenzymes in affinity chromatography has been reviewed.’ Other coenzymes, including nicot inamide nucleotides, phosphoenolpyruvate, and a flavin-like coenzyme from Mcrhartnhcrctrria, have also been the subjects for recent investigations. Enzymic mechanisms of phosphoryl transfer have been well reviewed’ and chiral [1s0,1i0,180]phosphatemonoesters have continued to be the subjects of intensive study.8 Considerations of space mean that this last topic can be fully ‘Phosphorus Chemistry directed towards Biology’, ed. W. J . Stec, Pergamon Press, Oxford, 1980. R. G . Shulman, T. R. Brown, K. Ugurbil, S. Ogawa, S. M. Cohen, and J . A . den Hollander, Science, 1979, 205, 160. 1 . D. Campbell, R. B. Jones, P. A. Kiener, and S. G . Waley, Biocheni. J . , 1979, 179, 607. J. D. Otvos, I . M . Armitage, J . F. Chlebowski. and J . E. Coleman, J . Bin/. Chetn., 1979, 254, 4707. D. E. Edmondson and T. L. James, Pro(.. Natl. Acad. Sci.USA, 1979, 76, 3786. ‘Methods in Enzymology’, Vol. 62, ed. S. P. Colowick and N . 0. Kaplan, Academic Press, New York, 1976. C. R. Lowe, Pure Appl. Chem., 1979, 51, 1429; E. Rieke. S. Barry, and K . Mosbach, Eur. J . Biochem., 1979, 100, 203. S. J . Abbott, S. R . Jones, S. A. Weinman, F. M. Bockhoff. F. W. McLatTerty, and J . R. Knowles, J . Am. Chrm. Soc., 1979, 101, 4323; M . K. Webb and D. R. Trentham. J . Biol. Chent., 1980, 255, 1775.

127

128


dealt with only once in this volume, and hence the reader is advised to consult Chapter 8 for a detailed treatment of this important subject. Another popular topic during the past year has been allylic pyrophosphates and the biosynthesis of isoprenoids.Y2 Coenzymes and Cofactors

Nicotinamide Coenzymes.-Structural analogues of A D P and NADi, u.g. 2'- and 3'-deoxy-NAD t , have been used to study the spatial requirements of the active site of NAD-specific isocitrate dehydr~genase,'~ and a spin-labelled relative of N A D P ?, i.e. adenosine 2'-phosphate 5'-diphospho-4-(2,2,6,6-tetramethylpiperidinyl-I-oxy) (I), which was prepared by the phosphoromorpholidate method, has been used to obtain information concerning the binding site of the coenzyme in dihydrofolate reductase.16Not surprisingly, ( I ) does not interact with a variety of dehydrogenases. Presumably the nicotinamide moiety must bind firmly to these enzymes, and analogues that lack this structural feature are inactive. Me

Me

0 \L, II o - N ~ o - - k - o - -I u - o /\

Me

Me

0

Ade

I1

I

"

OH

/

OH

nu

0

0

OH

OH

BrCH,CONH

OH

OH

(2)

Comparatively small changes in nicotinamide coenzymes can result in loss of enzymic activity; for example, substitution of a bromine atom at the 8-position in the adenine ring of NADP+ perturbs the conformation of the molecule suficiently to render it inactive.'' 4-(Bromoacetamido)phenyl uridyl pyrophosphate (2) is an active-site-directed irreversible inhibitor of uridine diphosphate galactose epirnerase, an enzyme which interconverts UDPGal and UDPGlc.18 The coQ

lo

l1 l2 l3 l5

D. E. Cane, Tetrahedron, 1980, 36, 1 109. J . W. Porter and S. L. Spurgeon, Pure Appl. Chem., 1979, 51, 609. H. C. Rilling, Pure A p p l . Chem., 1979, 51, 597. A. Saito and H. C. Rilling, J . Biol. Chem., 1979, 254, 851 1. T. Koyama, A. Saito, K . Ogura, and S. Seto, J . Am. Chem. SOC.,1980, 102, 3614. D. E. Cane and R. Iyengar, J . Am. Chem. Soc., 1979, 101, 3385. G . W . E. Plaut, C. P. Cheung, R . J . Suhadolnik, and T. Aogaichi, Biochemistr-v, 1979, 18, 3430.

l6

It(

L. Cocco and R . L. Blakley, Biochemistry, 1979, 18, 2414. M . A. Abdallah, M . J . Adams, I . G. Archibald, J . F. Biellmann, J . R . Helliwell, and S. E. Jenkins, Eur.J. Biochem., 1979, 98, 121. Y.-H.Huang Wong, F. B. Winer, and P. A . Frey, Biochemistry, 1979, 18, 5 3 3 2 .

Phosphates and Phosphonates of Biochemical Interest

129

enzyme for this reaction is N A D ’ , and this is alkylated on the adenine residue by (2),probably at N-1 or N-6, inhibiting the enzymic r e a ~ t i 0 n . l ~ Two papers have appeared concerning the analytical uses of nicotinaniide coenzymes. A simple, very sensitive method for the determination of picomole amounts of NAD+ has been deve1oped2O which relies on the coupled enzyme system hexokinase and NAD--pyrophosphorylase. In the presence of N A D ’ , 32P-labelled pyrophosphate is converted into [“2P]ADP,which is adsorbed onto charcoal before estimation. Procedures for the immobilization of N A D H have been developed which lead to a coenzyme that is more active than the soluble form.21 The insolubilized NADH has been re-cyclized with its oxidized form more than 10oO times without any indication of loss of activity.

Phosphoenolpyruvate.4 n a convenient adaptation of the Perkow route for the synthesis of phosphoenolpyruvate ( PEP),22as shown in Scheme 1 , pyruvic acid is converted initially into trimethylsilyl 2-trimethylsilyloxy-2-propenoate(31, followed by bromination of the latter to give trimethylsilyl 3-bromopyruvate (4). Treatment of (4) with dimethyl trimethylsilyl phosphite followed by sodium ethoxide gives the trisodium salt of P E P in high yield. H .O,POCCO,H

H,C=CCO,SiMe, CH,3COC0,H

I

OSiMe,

A BrCH,COCO,SiMe,

iii. iv

(4)

(3)

II

CH,

Reagents: i . MesSiCI.Et:gN: ii. Br?; i i i , Me&OP(OMe).: iv. NnOEt

Scheme 1

\

OMe ( 6 )

Methyl acetylphosphonic acid (5) is a potent inhibitor of pyruvate dehydro~ because it adds on genase and pyruvate oxidase from Escherichia ~ o l i , ‘probably to thiamine pyrophosphate in a manner similar to the natural substrate pyruvate to give (6). The latter does not eliminate methyl metaphosphate and hence the enzymic reaction cannot proceed. Racemic (6) has been synthesized by treating thiamine pyrophosphate with (5).24 Addition of (6) to pyruvate dehydrogenase that is lacking in thiamine pyrophosphate activates the enzyme, and thiamine

23

Y.-H. Huang Wong and P. A . Frey, Biochetiiistr),, 1979, 18, 5337. C. P. Cheung and R. J. Suhadolnik, Anal. Biochenr., 1979, 97, 309. C. W. Fuller, J . R. Rubin, and H. J . Bright, Eur. J. Biockenr., 1980, 103,421. M. Sekine, T. Futatsugi, K. Yamada, and T. Hata, TcJtruhedronL e t t . , 1980, 21, 371. T. A . O’Brien, R. Kluger, D. C . Pike, and R. B. Gennis. Biochini. Biophvs. Acru, 1980. 613,

21

R. Kluger and D. C. Pike, J. A m . Clrem. Soc., 1979, 101, 6425.

Zo 21

B2

10.

130

Organophosphorus Chemistrj!

pyrophosphate is produced. Thus, one enantiomer of the inhibitor must bind to the active site of the enzyme in a manner analogous to the natural substratecoenzyme complex. Pyridoxal Phosphate.-A variety of reactions of amino-acids are catalysed by pyridoxal-phosphate-dependent enzymes, and these have been reviewed recently.25In the presence of metal ions, pyridoxal itself can catalyse such elimination reactions as the elimination of phosphate from O-phosphothreonine.26 The crystal structures of the nickel(i1) and copper(I1) complexes of the O-phosphothreonine-pyridoxal Schiff base have now been published*’ but do not shed much light on the elimination mechanism, as they are different from one another. Furthermore, the labile C-H bond is not in a correct orientation for easy bond breaking in either structure. Phosphorus-31 n.m.r. is a much more useful technique for investigating the complexes formed between paramagnetic ions and pyridoxal phosphate, as both the structure of the complexes and the ionization state of the pyridoxal phosphate can be determined.28 Other Coenzymes.-The structure of coenzyme Flea (7; R = P03H2),a cofactor for the hydrogenase in Methanobacterium brjiantii, was deduced from n.m.r. and U.V.data.2BSynthetic proof has now been obtained from two groups for the 8-hydroxy-10-methyl-5-deazaisoa11oxazine ring The synthetic riboflavin analogue (7; R = H) was identical with the product obtained by the acid hydrolysis of (7; R=PO,H,).

:-~-””

C H 2( C HO H ),C H,O R I

CHO

t+z;

Oti

H

0 (7)

Cti,PO,H, (8)

C 111cf 4 *PO3i 1 (9)

Two unusual nucleoside phosphate sugars which have been isolated recently are WDP N-acetylgalactosamine 6-sulphate, from quail egg-white,31 and C M P N-acetylneuraminic acid in liver or kidney.32The formation of the latter from exogenous radioactively labelled N-acetylneuraminic acid is claimed to be the first proof of its participation in sialic acid metabolism.

3 Sugar Derivatives u-Erythrose 4-phosphonate (8) and 4-homophosphonate (9), which can be prepared by the oxidation of the comparatively readily available D-glucose 625 2(i

27

3s 20

30

D. E. Metzler, A&. Enzymul. Relat. Areas Mol. B i d . , 1979, 50, 1 . Y. Murakami, H. Kondo. and A. E. Martell,J. Ant. Chem. Suc., 1973,95,7138. K . Aoki and H . Yamazaki, J . C h r m . Soc., Chem. Commun., 1980, 363. M . Hoerl, K . Feldmann, K . D. Schnackerz, and E. J . M. Helmreich, Bioc~hcriristrl..197’). 18, 2457; T. S. Viswanathan and T. J. Swift, C a n . J . Cheni., 1979,57, 1050. L. D. Eirich, G . D. Vogels, and R . S. Wolfe, Biochemistry, 1978, 17, 4583. W. T. Ashton, R . D. Brown, E. Jacobson, and C. Walsh, J . Am. Clwrn. Soc., 1974, 101, 4419; A. Pol, C. van der Drift, G . D. Vogels, T. J . H. M . Cuppen, and W. H . Laarhoven, Biochem. Biophys. Rev. Commun.. 1980, 92, 255.

:I1

Y . Nakanishi, S. Okuda, M . Tsuji, and S. Suzuki. Biodiim. Biup1ij.s. Ar,tu. IY79. 564, 8. D. J . Carey and C. B. Hirschberg, Bioc~/temi.sfrI*, 1979, IS, 2086.

131

Phosphates and Phosphortates of' Biochemical Iiiterest

phosphonate and 6-homophosphonate with lead tetra-acetate, behave as substrates for a number of enzymes which normally require D-erythrose 4-phosphate.'" This indicates that the oxygen atom attached to C-4 in the erythrose phosphate does not play an important part in determining the conformation of the enzyme-substrate complexes. Phosphonate and homophosphonate analogues of 3-deoxy-~-crrahirio-heptulosonate7-phosphate and D-gluco-heptulosonate have also been prepared.34 Both are competitive inhibitors of 3-dehydroquinate synthetase in E. coli; surprisingly, the phosphonate analogues have a higher affinity for the enzyme than the homophosphonates. 4 Phospholipids

Glucosyl phosphatidylglycerol ( 10) has been prepared by a phosphotriester route, using methodology developed for the synthesis of oligonucleotide^.^^ The yields are good, and there appears to be little migration of groups during the synthesis. An alternative method of phospholipid synthesis involves cyclic me-diol phosphates, and this route has been used to prepare analogues of cardioand also nucleolipids, e.g. (12).:17Two fluorescent phospholipids have lipin ( 1

0RCo2foCou r-0-P-0

I

" I

_1

0 Me(CH2),, O -

ti0

~

OH

-

O

HO

~

A

d

e

OH

(11) P. Le Marechal, C . Froussio5. M . Level. and R . A ~ r i i d Hiochctu. . Biop/ij.s.

RCS.C o n i t ~ i u r i . .

1980, 92, 1097. 1'. Le Marechal, C . Froussios. M . Level, and K . Azerad. Biochctn. BiopllyT. R P Y .C o i ? i n i i l u . , 1980. 92, 1104. C. A . A . van Boeckel and J . H . van Boont. Tt,truhcdroti Lvtt., 1979, 3561. S. Rainier, M. K . Jain, F. Kaniirez, 1'. V. Ioannou, J . F. Marecek, and R. Wagner. Bio~./iitti. Bioph~.s.Almtci, 1979, 558, 187. J . Smrt and S. Hynie, Collvcr. Cxc.11. Clic.t?i.Cotiimitn., 1980. 45, 927.

132

Organophosphorus Chemistrji

been synthesized to assist the study of phospholipid bilayers. Treatment of phosphatidylethanolamine with o-phthalaldehyde and 2-mercaptoethanol gives a fluorescent product, probably 1-(2'-thio-l '-hydroxyethyl)-2-(ethylphosphatidyl)isoindole (13).38Although (13) does not form stable vesicles on its own, it can form stable vesicles in the presence of phosphatidylcholine. 1,2-Bis-[o-(1-pyreno)decanoyll-sn-glycero( 3)phosphocholine (1 4), prepared from the acid chloride ( 15) and the cadmium chloride complex of sn-glycero(3)phosphocholine, intercalates in a well-ordered fashion in very hydrophobic bi1aye1-s.~~

Pyr(CH,),COCI + (15)

f0;

-OCO(C H 2)v Py r __f

OPOCH,CH,A Me,

I

0-

Pyr(CH,),C02-

0

II I

-OPOCH,C H$ Me 0-

(14)

An enzymic synthesis of sn-glycerol 3-phosphate has been described which is based on the phosphorylation of glycerol using immobilized glycerol kinase and ATP, the latter being regenerated by using ADP and acetyl phosphate.40The yields are impressive, and so-glycerol 3-phosphate, together with its 2-2H- and 3-2H-derivatives, can be prepared on a scale of 100 grams. Although the yields are not so impressive as in the previous method, germinating soya beans are a simple way of converting 32P-labelled orthophosphate into [32P]phosphatidylcholine and [32P]lysophosphatidylcholine.41 The structures of the lipopolysaccharides from a heptose-less mutant of E. coli have been identified as (16;R=P03H2)and (16;R=P,0,H3) by degradation and n.m.r. The relative proportions of the two lipopolysaccharides depend on the composition of the growth medium, (16; R = P03H2)predominating in phosphate-deficient media. The structure of this lipopolysaccharide is very 3H 39 40

41

42

B. C. Chang and L. Huang. Biochim. Biophys. Arfa, 1979,556, 52. J . Sunamoto, H. Kondo, T. Nornura, and H. Okarnoto,J. Am. Chem. Snc., 1980, 102, 1146. V. M . Rios-Mercadillo and G . M . Whitesides, J . Am. Chem. Sac., 1979, 101, 5828. F. H . Hubmann, Biochem. J., 1979, 179, 713. M . R . Rosner, H . G. Khorana, and A . C . Satterthwait, J . Biol. Chem., 1979, 254, 5YO6, 59 18.

Phosphates and Phosphonates of Biochemical interest

133

H,OJ'O&oHO

CH2

I

CHOH

I

I

co I

(16)

(17)

CH20COR

similar to the Lipid A which is found in Salmonella.43The structure of a phosphoglycolipid from Acholeplasma granularum has been assigned as (1 7), which is unique as it contains not only a phosphotriester group but also glucose moieties in different anomeric configuration^.^^ However, the structure is open to question, as the phospholipid is acidic, and there are no obvious acidic groups in (17). The application of an automated phosphate analyser to the analysis of phospholipids has been described.45 5 Phosphonates

3-( N-Acetyl-N-hydroxyamino)propylphosphonic acid (18 ; R = MeCO) and its N-formyl analogue (1 8; R = CHO) have recently been isolated from a strain of S t r e p t o m y c e ~Both . ~ ~ are inhibitors of biosynthesis of cell walls in Gram-negative bacteria. A synthetic route to (1 8 ;R = MeCO) has been developed, starting from 3-( N-tosyl-N-benzy1oxyamino)propyl bromide (1 9) ; when treated with sodium 43 44

45 46

M. R . Rosner, R. C. Verret, and H . G . Khorana, J . Biol. Chem., 1979, 254, 5926; P. F. Muhlradt, V. Wray, and V. Lehmann, Eur. J . Biochem., 1977,81, 193. P. F. Smith, K . R . Patel, and A, J. N . Al-Shamman, Biochim. Biophys. A d a , 1980,617,419. P. J. Geiger and C. M. Roberts, Biochem. Biophys. Res. Commun., 1979, 88, 508. T. Kamiya, K. Hemmi, H . Takeno, and M . Hashimoto, TerrahedronLerr., 1980, 21, 95.

134

Organophosphorus ChernistrJ3 OH

I RNCH,Cli,CH,PO,Ii,

OCH,Ph

Me

(18)

\

0

(22)

(23)

diethylphosphonate, this yields the phosphonate (20). Hydrolysis of the latter in HCI-HOAc gives (18; R = H), which can be acetylated to produce ( I 8 ; R = MeCO). Two other phosphonate antibiotics, i . ~ (2R)-3-(N-acetyl-N-hydroxy. amino)-2-hydroxypropylphosphonic acid ( 21 ) and 3-(N-hydroxyamino)-l-(€)propenylphosphonic acid (22), have also been isolated from Strrptom.vces species.47Both (21) and (22), together with their N-formyl congeners, have been synthesized. The key steps in these syntheses are nucleophilic displacement reactions by N,O-bis(ethoxycarbony1)hydroxamide on diethyl 2-hydroxy-3tosylpropylphosphonate o r diethyl (€)-3-bromopropenylphosphonate (23). The mechanism of action of these antibiotics is not known, although they are clearly members of the same family.

When I-pyrroline trimer (24) is heated with diethyl phosphite under a n inert atmosphere, the diethyl ester of racemic 2-phosphonopyrrolidine (25; R = H ) is Treatment of the latter with 3-(acety1thio)propanoic acid and DCC gives the diethyl ester of (25; R = MeCOSCH,CH,CO). Removal of the ethyl groups with trimethylsilyl bromide and of the acetyl group with hydrazine yields ( 2 5 ; R = HSCH,CH,CO). This compound has biological activity, resembling (26) because it is an inhibitor of the angiotensin-converting enzyme.P' JH

.Iy

M . Hashimoto, K . Hemmi. H. Takeno. and T. Kamiya, Tctruhedron LtJtt.,1980, 21, 99. E. W. Petrillo, Jr., and E. K. Spitzmiller, Tc.truhdron Lctf., 1979, 4929. D. W . Cushman, H . S. Cheung, E. F. Sabo, and M . A. Ondetti, Biochct??i\tri..1977. 16,

5484.

Phosphntes and Phosphonates of Biochemical

i i i terest

135

In Tetrahyrnenn pyrifi,rmis, the metabolism of 2-amino-3-phosphonopropionic acid (27) is catabolized by deamination to 3-phosphonopyruvic acid (28) followed by decarboxylation to 2-phosphonoacetaldehyde. This can either undergo dephosphonylation to produce acetaldehyde or can undergo amination to produce (2-aminoethyl)phosphonic acid.50 Analogues, e.g. (29) and (30),of naturally occurring biologically active phosphates have been prepared in which a phosphoryl group has been replaced by a methylphosphonyl group.51 In general, the analogues are either inhibitors of enzymes or are inactive. This suggests that the methylphosphonyl group cannot be transferred enzymically and that dissociative mechanisms involving metaphosphate may be involved. However, the shape and metal-binding properties of the analogues must differ from the natural compounds, and this may account for their inactivity.

A series of phosphonate monoesters and phosphate diesters have been prepared in which the shapes and leaving-group abilities of the substituents have been systematically varied.5z These compounds have been tested as substrates for 5’-nucleotide phosphodiesterase. Aliphatic monoesters of phosphonates were not hydrolysed, regardless of shape, and kinetic evidence suggests that the substrates bound in two different modes, only one of which was productive. N-0-(Phosphonoacety1)-L-ornithine(31) is an inhibitor of the biosynthesis of citruiline (32), as it is a transition-state analogue of the reaction that is catalysed by L-ornithine carbamoyltran~ferase.~~ However, (31 ) does not cross the bacterial cell membrane, and a tripeptide, glycylglycyl-N-6-(phosphonoacetyl)-L-ornithine, has been synthesized to make use of the broad-spectrum tripeptide permease of E. c 0 1 i . ~The ~ tripeptide is taken up by E. coli and is probably cleaved inside the cells, as it inhibits their growth after an initial lag phase. 51 B2

51

A . Horigane, M . Horiguchi. and T. Matsumoto, Bictchitn. Biophys. Actcr, 1980,618, 383. R . A . Lazarus, P. A. Benkovic, and S.J. Benkovic, Arch. Biochem. Bioph?~.s.,1979. 197, 1 1 8 . M . Landt, R . A. Everard, and L. G . Butler, Biochonistry, 1980, 19, 138. N. J. Hoogenraad, T. M . Sutherland, and G . J. Howlett, Eur. J. Biocheni., 1979, 100, ROY. M . Penninckx and D. Gigot. J. B i d . Chem., 1979, 254, 6392.

136

Organophosphorus Chemistrji COCH2P0,H,

CONH,

CH

CH

I

I

Diagnostic nuclear medicine frequently involves the absorption by a patient of a compound that contains an isotope that emits prays; the compound can then be localized within the body by using a pray camera. A recent development of this technique has been the preparation of the BsT~-methylenedipho~phonate complex, which has been used to image the regions of the body where pyrophosphate is concentrated, particularly bone.55 6 Enzymology Enzyme Mechanisms.-Muscle c o n t r a ~ t i o n ,the ~ ~ synthesis of phosphoribosyl pyrophosphate in mammalian cells,57and positional isotope-exchange studies on enzyme mechanismsK*have all been reviewed recently, and the multiple l80labelling of orthophosphate from ['*O]water has been used to probe the catalytic mechanism of fructose 1, 6-bisphosphata~e.~~ Stopped-flow measurements o n fructose 1,6-bisphosphate aldolase show that the enzyme reacts with dihydroxyacetone phosphate to form an acid-labile intermediate which is in rapid equilibrium with an enamine.eo CHO

I I

CH, CH,OPO,H ,

(33)

+OH C H,OPO,H (34)

Phosphorylation of 3-hydroxypropionaldehyde diethyl acetal gives the 3phosphate, which can be isolated as the barium salt. Treatment of the latter with an acidic ion-exchange resin liberates 3-hydroxypropionaldehyde 3-phosphate (33), which is a substrate analogue of glyceraldehyde 3-ph0sphate.~' While the monoanion of (33) is comparatively stable, the dianion catalyses its own decomposition, and at 25 "C it has a half-life of ca. 30 min. Erythronate 4-phosphate (34), 55 56

57

5M 51)

6o

K. Lisbon, E. Deutsch, and B. L. Barnet, J. Am. Chrm. SOC.,1980, 102, 2476. E. W. Taylor, CRC Crit. Rei.. Biochem.. 1979, 6, 103. M . A. Becker, K. 0. Raivio. and J. E. Seegmiller, Adc. Enzymol. Rrlur. Arras Mnl. B i d . , 1979, 49, 28 I . 1. A. Rose, Adu. Enzymol. Relat. Areas Mol. Biol., 1979, 50, 361. T. R. Sharp and S . J. Benkovic, Biochemistry, 1979, 18, 2910. E. Grati and G . Trombetta, Eur. J . Biochem., 1979, 100, 197. A. R. Gallapo and W. W. Cleland, Arch. Biochem. Biophys., 1979, 195, 152.


137

prepared by the oxidation of Derythrose 4-phosphate with aqueous bromine, is a strong inhibitor of ribose 5-phosphate isomerase.62 It is postulated that (34) resembles an ene-diol intermediate which is formed in the reaction, and that the isomerization is similar to those catalysed by glucose 6-phosphate isomerase and triose phosphate isomerase. The enzymic conversion of D-ribulose 1,5-bisphosphate into glycerate 3-phosphate is not entirely stereospecific; 10% of the L- and 90% of the D-isomer are formed.s3 L-Glyceric acid 3-phosphate appears to be the primary substrate for photorespiration.s4

- oy;n

CH(OH)CH(OH)CH,OPO,H,

HO

OH (35)

H

"

(36)

1

(37)

(5-Phosphoribosy1)anthranilate(35) isomerase and indoleglycerol-phosphate synthetase catalyse two metabolic steps of tryptophan biosynthesis. The isomerase catalyses the Amadori rearrangement of (35) to (36) and the synthetase the ringclosure of (36). In E. coli, a single protein chain contains both these catalytic activities. Reduction of (35) with borohydride leads to the formation of (37), which can be regarded as either a product analogue of the isomerase or a substrate analogue of the ~ y n t h e t a s e Hence, . ~ ~ (37) should bind to two different sites on the single protein chain of the E. coli enzyme. This has been demonstrated by fast reaction studies.es It has been claimeds7 that inorganic phosphate is a substrate for at least 58 different enzymic reactions. The effect of a number of inorganic ions, other than ort hophosphate, on glyceraldehyde 3-phosphate dehydrogenase has been investigated. Most tetrahedral oxyanions, e.g. arsenate and molybdate, are substrates, apart from sulphate and selenate. Tetrahedral monoanions such as [ReO,]- and [GeO(OH),]- bind to the enzyme but are not substrates. In another study, 29 pyrophosphate analogues were tested for their ability to inhibit the

64

W. W. Woodruff, 111, and R. Woolfenden, J . Biol. Chem., 1979, 254,5866. R . Brindkn, T. Nilsson, and S. Styring, Eiochem. Biophys. Res. Commun., 1980, 92, 1297. R . Branden, T. Nilsson, S. Styring, and J . Angstrom, Biochem. Biophys. Res. Commun.,

85

H. Bisswanger, K . Kirschner, W. Cohn, V. Hager, and E. Hansson, Biochemistrjl, 1980.

62

63

1980.92, 1306.

19, 5946.

68

67

W. Cohn, K. Kirschner, and C. Paul, Biochemistry, 1979, 18, 5953. L. D. Byers, H. S. She, and A. Alayoff, Biochemistry, 1979, 18, 2471.

138

Organophosphorirs ChemistrjH0 , C PO,H

(38)

HO,CCH,PO,H,

(39)

activity of the DNA polymerase from Herpes simplex virus type I . Phosphonoformate (38) and phosphonoacetate (39) were the most effective inhibitors.'j8 Phosphopr0teins.-The phosphorylation and dephosphorylation of enzymes has been reviewed,69and ever more examples of phosphorylated proteins are being reported at a rapid ~ a t e . ~ OSome - ? ~ sequence work has been carried out on the phosphorylated proteins, ranging from the simple peptide mapping of nonhistone nuclear proteins 74 to detailed sequence studies of fructose 1,6-bisphosphatase, 75 phenylalanine hydroxylase,76 and a highly acidic region of a nuclear non-histone protein.'? A major phosphoprotein that is involved in the phosphoenolpyruvate-dependent transport of sugars in E. coli has been isolated.7n Phosphorus-31 n.m.r. evidence indicates that the phosphoprotein contains a phosphorylated histidine residue and that the protein can exist in two conformations, depending on the protonation state of the reactive histidine residue. Galactose 1-phosphate uridylyl transferase is an enzyme which will interconvert galactose 1-phosphate and UDPGlc with glucose 1-phosphate and UDPGal. Not surprisingly, a covalently bound uridylyl-enzyme intermediate is formed as an intermediate in this interconversion, and degradative studies with radioactively labelled material indicate that the uridylyl residue is attached to N-3 of a histidine residue. 79 The binding of metals by phosphoproteins is important nutritionally, and so it is of interest to determine the strength with which iron(rr1) ions are bound by phosvitin and casein.8oAnalysis of the data for phosvitin suggests that clusters of di-phosphorylserine residues in both proteins bind to iron(rr1) ions with stoicheiometric equilibrium constants in the region of lo1?to 1020.The binding of the iron is mostly intramolecular, and the intermolecular binding only occurs when most of the binding sites are filled.81 The alkaline lability of serine and threonine phosphate esters in phosphoproteins has been used for some time as a diagnostic test for their presence.82A recent study using model phosphopeptides shows that Hu

7u 71

72

73

75

77 7H 71)

"1

x"

B. Eriksson. A. Larsson. E. Helgstrand, N . G . Johansson, and B. Oberg, Biodiitri. Biop/i.i.c. Actu, 1980, 607, 53. G . Krebs and J . A. Beavo, Annir. RPr. B i o c h ~ t ~ i1979, ., 48, 923. K . S. Lam and C. B. Kasper, Proc. Natl. Acarl. Sci. U S A , 1980, 77, 1927. V. Ernst, D. H . Levin, A . Leroux, and 1 . M . London, Proc. N a t l . A c a d . Sci. U S A , 1980. 77, 1286. A. A. DePaoli-Roach, P. J . Roach, and J . Lamer, J . B i d . C h m t . , 1979, 254, 12067. T. R. Soderling, A. K . Srivastava, M . A . Bass, and B. S. Khatra. Pro(.. Natl. Acacl. Sci. U S A , 1979, 76,2536. C . E. Jones, H. Busch, and M. 0. J . Olson, Biochem. Biophys. R r s . Commun., 1979. 90, 734. E. Humble, U . Dahlqvist-Edberg, P. Ekman, E. Netzel, U . Ragnarsson. and L. Engstroni. Biochent. Biophj*.s.Rrs. Contmun., 1979, 90, 1064. M. Wretborn, E. Humble, U . Ragnarsson. and 1.. Engstrom, Biochrtri. Bioph\~\. K c s . Commun., 1980, 93, 403. M . D . Mamrack, M. 0. J . Olson, and H . Busch, Biochemistry, 1979, 18, 3381. G. Dooijewaard, F. F. Roossien, and G . T. Robillard, Biochrmisrr~.,1979. 18, 2906. S.-L. 1.Yang and P. A. Frey, Biochi>mistrlp, 1979, 18, 2980. J . Hegenauer, P. Saltman, and G. Nace, Bin('/tC,titi.Ytri,.1979, 18, 3865. G . Taborsky, J . B i d . Chem., 1980, 255, 2976. G . Taborsky, A h . Protein Chent., 1974, 28, I .

Phosphates and Phosphottates of Biochemical Interest

139

phosphothreonine residues are more alkali-stable than phosphoserine residues.83 Interestingly, the octapeptide Arg-Arg-Arg-Arg-Pro-Thr(P)-Pro-Ala-NH,, which corresponds to a sequence in a natural substrate of CAMP-dependent protein kinase, is stable to 1 M alkali over 18 h at room temperature. The enzyme CAMPdependent protein kinase will also phosphorylate the serine residue in N-acyl and N-dansyl derivatives of Leu-Arg-Arg-Ala-Ser-Leu-Gly (this amino-acid sequence also occurs in porcine pyruvate kinase),B4and the hydroxyproline in Leu-ArgArg-Ala-Hyp-Le~-Gly."~ y-Glutamyl phosphate has been reported to be present in chicken bone collagen.B6This is the first time that a reactive acyl phosphate has been discovered in a structural protein, but it may be an artefact, as such compounds are usually readily hydrolysed. 7 Other Compounds of Biochemical Interest As mentioned in the Introduction, the biosynthesis of isoprenoids has attracted attention in the past year. The stereochemistry of allylic pyrophosphate metab o l i ~ m the , ~ biosynthesis of carotenes,lO and prenyl transferasell have all been reviewed. The last enzyme catalyses the condensation of isopentenyl pyrophosphate with an allylic pyrophosphate to produce the next higher homologue. Binding studies using inorganic pyrophosphate as a substrate analogue indicate that the pyrophosphate moiety of farnesyl pyrophosphate binds in the allylic portion of the catalytic site in a non-productive manner which excludes water from participating in the solvolysis of the pyrophosphate.12 The substrate specificity of prenyl transferase has been studied,13 and lB0-labellingexperiments show that there is ion-pair formation in the rearrangement of farnesyl pyrophosphate to nerolidyl pyrophosphate.14 Citric acid 3-phosphate (40) inhibits the growth of hydroxylapatite crystals and may play a role in biological calcification. Two syntheses of (40) have been published within the past year, both starting from triethyl citrate (41). In one synthesis, the free hydroxyl group in (41) is phosphorylated with o-phenylene phosphorochloridate, which is later removed by hydrogenolysis [Scheme 2(a)]." I n the other [Scheme 2(b)J, (41) is phosphorylated with 2-cyanoethyl phosphate C H,CO,E t

HO+-CO,Et CH,CO,Et

(b) iv, iii

CH,CO,H I

H,O,PO+-CO,H CH,CO,H (40)

(41)

Reagents: i , o-phenylene phosphorochloridate; i i , H2,PtO.r; iii. Ca2+. OH O P 0 3 H2. d icyclohexylcarbodi-imide(DCC)

; iv,

NCCH2CHr-

&heme 2 HZ

#5 HR

X i

B. E. Kemp, FEBS Left., 1980, 110, 308. B. E. Kemp, J. Biol. Chent., 1980, 255, 2914. J. R. Feramisco, B. E. Kemp, and E. G. Krebs, J. Biol. Chcnr., 1979, 254, 6987. L. Cohen-Solal. M. Cohen-Solal, and M. J. Glimcher, Proc. N o t / . Acntl. Sci. USA, 1979. 76, 4327. W. P. Tew, C. Mahle, J . Benavides, J . E. Howard, and A . L. Lehninger, Bioclrcmistri~. 1980, 19, 1983.

140


and DCC, the protecting group in this case being removed by alkaline hydrolysis.88In both syntheses, the triethyl ester is saponified by alkali in the presence of calcium ions and (40) is isolated as the calcium salt. If calcium ions are omitted from the saponification, then the monoethyl ester is the major product, and not (40). Barbituric acid reacts spontaneously with D-ribose 5-phosphate to give a series of compounds (depending on the reaction time), all of which are powerful inhibitors of orotidine decarboxylase and hence are of interest as potential anti-cancer compounds.8eStructures (42) and (43) have been assigned to two of

HO

OH

HO

(42)

OH (43)

OPO, H, I

OPO,H,

these adducts on the basis of spectroscopic data. However, these structures must be open to question, as they are both imidoyl phosphates and are highly reactive P-XYZ s y ~ t e r nThe ~ . ~analogous ~ compounds formed from phosphomonoesters and DCC have never been isolated, and heterocyclic imidoyl phosphates such as pyridyl 2-phosphates are unstable in neutral or acid solution, although they are reasonably stable in Other anti-tumour compounds which have been investigated in the past year are cyclophosphamide, together with its analogues,e2 and [12sI]Synkavit(44).93 Williams and J . D. Sallis, Anal. Biuchem., 1980, 102, 365. H. Komura, K . Nakanishi, B. W. Potvin, H. J . Stern, and R. S. Krooth, J . Am. Chrm. Sot .,

* t ~G. ” @

1980, 102, 1208.

go

91 *2 93

V. M. Clark and D. W. Hutchinson, Progr. Org. Chem., 1968, 7, 75. W. Kampe, Chem. Ber., 1965, 98, 1038; V . M . Clark, D. W. Hutchinson, and D. E. Wilson, Angew. Chem., 1965,77,259. K . Pankiewicz, R . Kinas, W. J. Stec, A. B. Foster, M . Jarman, and J . M. S. Van Maanen, J , Am. Chem. SOC.,1979, 101, 7712. I. Brown and J. S. Mitchell, J . Chem. Suc., Chem. Commun., 1979, 659.


141

H2NocXNH(H0

OHCHN

NH

I

I

Ribp (45)

Ribp

Ribp = ribosyl 5-phosphate

(46)

The newly discovered ( E)-afi-diformamido-[l-( 5’-phosphoribosylamino)acrylamide (45), which can be prepared by treating 5’-phosphoribosyl-5-amino-4imidazolecarboxamide [AICAR, (46; R = H)] with formic acid and acetic anhydride, is a possible intermediate in purine b i o s y n t h e ~ i s .Its ~ ~ substrate activity for the IMP-synthesizing enzyme complex is very similar to that of formyl-AICAR (46; R = CHO). In the enzymic reaction, which is catalysed by creatine kinase: creatine phosphate

+ ADP +creatine + ATP

the standard free-energy change favours ATP formation, and hence creatine phosphate (47) can be regarded as a reservoir for ATP in systems such as contracting muscle. 1-Carboxymethyl-2-iminoimidazolidine [cyclocreatine] is an excellent substrate for creatine kinase and is phosphorylated by this enzyme.Q5The structure of phosphorylated cyclocreatine (48) has been the subject of some but, now that the crystal structure of the dilithium salt of (48) has been published,g7 deductions can be made concerning the geometry of the active site of creatine kinase. OH 0-P-

/

NH

Me (47)

(48)

A number of papers have appeared on analytical techniques that can be

applied to biologically important organophosphorus compounds. These include improvements to an enzymic assay for inorganic orthophosphate,g8automated chromatography for phosphate and the estimation, by h.p.l.c., of phosphate esters in beating rat hearts.loOPhosphonic acids, e.g. 4-aminobenzylphosphonic acid, have been used as ligands in the purification of human red-cell acid phosphatase by affinity chromatography.101 J . E. Baggott and C. L. Krumdieck, Biochemistry, 1979, 18, 3501. T. M. Annesley and J. B. Walker, J . Biol. Chem., 1978, 253, 8120. ** ti. E. Struve, C. Gazzola, and G . L. Kenyon,J. Org. Chem., 1977,42,4035; G . L. Rowley, A. L. Greenleaf, and ti. L. Kenyon, J . Am. Chem. SOC.,1971, 93, 5542. 9 7 ti. N. Phillips, Jr., J . W . Thomas, Jr., T. M. Annesley, and F. A. Quiocho, J . Am. Chem. SOC.,1979, 101, 7120. *13 N. W. Cornell, M. G. Leadbetter, and R . L. Veech, Anal. Biochem., 1979,95, 524. P. J . Geiger and C. M. Roberts, Biochem. Biophys. Res. Commun., 1979, 88, 508. l o o C. M . Roberts and S. P. Bessman, Biochem. Biophys. Res. Commun., 198U, 93, 617. lnlJ . Dissing, 0. Dahl, and 0. Svensmark, Biochim. Biophys. Acta, 1979. 569, 159. 95

8

Phosphoryl Transfer from Phosphornonoesters and Adenosine 5'-Triphosphate BY F. R A M I R E Z AND J. F. MARECEK

Nucleophilic displacements at the phosphorus atom of esters of phosphoric and pyrophosphoric acids fall into two discrete categories o n the basis of the type of mechanism by which the ester transfers its phosphoryl group to the nucleophile. This Report summarizes our studies on phosphoryl transfer from phosphonionoesters in aprotic and protic solvents' and more recent work on non-enzymatic transfer of the terminal Py group of adenosine 5'-triphosphate (ATP) to alcohols and water.' I n addition we present data o n the distribution of oxygen isotopes in the inorganic phosphate (Pi) obtained when [;I-l80.]ATP is hydrolysed in water under catalysis by skeletal muscle actomyosin and by various enzymatically active proteolytic subfragments from myosin. These data bear o n the chemical mechanism of cleavage of MgATP at the active site of an enzyme, and provide evidence for the existence of two kinds of active site in myosin, differing in their rates of intermediate oxygen exchange. 1 Types of Phosphoryl Transfer ( i ) Phosphotriesters and non-ionized phosphodiesters and phosphomonoesters react by an addition-elimination mechanism which probably involves an oxyphosphorane intermediate3as shown in reaction ( I ) .

R',R2 = alkyl or aryl; R'

,j

= alkyl o r aryl,

Rz= H ; or R',R' = H

F. Kaniirez and J . F. Marecek, ( u ) J. Am. Cfietti. S O L . . , 1979, 101, 1460; ( h ) Tctrahc~~O-orr, 1070, 35, 1581; (c) Tctruhdrori, 1980, 36, 3151 ; ( ( 1 ) Pure Appl. ChPrn., 1080, 52, 1011. F. Rarnirez, J . F. Marecek, and J. Szarnosi, J. O r g . Chrm., 1980.45. 4748: F. Karnire7 a n t i J. F. Marecek, Pure. Appl. Chcrn., 1980, 52, 22 13. 'Organophosphorus Stereocheniistry', ed. W. E. McEwen and K. D. Berlin, Dowdeil. Hutchinson, and Ross, Stroudburg, Pa., 1975, Vols. I and 11; F. Rarnirez. B. Hansen, and N . B. Desai, J . A m . Cliem. Soc., 1962, 84, 4588; F. Ramirez, 0. P. Madan, N. B. Desai. S. Meyerson, and E. M. Banas, ibid., 1963, 85, 2681; F. H. Westheimer, Act. Chrni. Rcs., 1968, 1, 70; P. Gillespie, F. Ramirez, I . Ugi, and D. Marquarding, Atrgew. Chctti., / t i t . Ed. EngI., 1973. 12, 91 ; F. Kamirez, M. Nowakowski, and J. F. Marecek. J . A t t i . C h t i i . Soj1P n.m.r. spectrometry.lb We have been unable to demonstrate the occurrence of nucleophilic catalysis in monoester dianions XP032-in protic or aprotic solvents, and have suggested that the slight acceleration of the rate of displacements on dianions which is observed in aqueous and alcoholic solutions in the presence of pyridine and most tertiary amines is due to medium effects that are not related to nucleophilic cata1ysis.l Structural factors in the monoester control the relative tendencies for the elimination-addition and the addition-elimination mechanisms. These structural factors are interrelated, as illustrated by members of the aryl phosphate series. ( i ) 2,CDinitrophenyl phosphate is a stronger acid than 4-nitrophenyl phosphate. (ii) The phosphorus atom of the dinitro-ester is more electrophilic than that of the mononitro-ester, and hence the former has a greater tendency to form phosphoranes than the latter. (iii) 2,4-Dinitrophenoxide is more nucleofugic than 4-nitrophenoxide, and, therefore, the dinitro-ester dianion has a greater tendency to decompose into PO,- and aryloxide ion than the mononitro-ester dianion. (iv) The ester-oxygen of the dinitro-monoanion is less basic than that of the mononitro-monoanion; consequently, the proton shift which seems to be necessary for the formation of PO,- from monoanion is disfavoured in the

7

F. Ramirez, J . F. Marecek, and H . Okazaki,J. Am. Chrm. Sac., 1976,98,5310; F. Ramirez, J. F. Marecek, H . Tsuboi, and H . Okazaki, J . U r g . Chenz., 1977, 42, 771 ; F. Ramirez and J. F. Marecek. Tetrahedron Lett., 1976, 3791 ; F. Ramirez and J . F. Marecek, ibid., 1977, 967. R. Blakeley. F. Kerst, and F. H . Westheimer. J. A n ] . Chent. Sac., 1966, 88, 112.

Phosphoryl Transfer from Phosphornonoesters and Adenosine 5'-Triphosphate 14 5

dinitro-ester relative to the mononitroester: ArOP03H-

+ArO(H)P032-

ArOH

+

POa-

The electronic factors that are responsible for these differences in the aryl phosphates and in the corresponding aryloxide ions are, of course, reflected in the acidity of the respective compounds. The monoanions XP03H- and the phenols XH in the series 2,4-dinitrophenyl, 4-nitrophenyl, phenyl, and alkyl have the following pKa values in water: 4.6, 4.1; 5.5, 7.2; 6.2, 10.0; and 7.2, 15. Excepting the 2,4-dinitrophenyl derivatives, the nucleofugic group XH is a weaker acid than the corresponding monoanion XP0,H-. Conversely, the nucleofugic anions X - are stronger bases than the phosphate dianion XP032-in all cases except 2,4-dinitrophenoxide, which is a weaker base than the XPO," dianion. The consequence of these differences on the mechanisms by which the esters react in their various states of ionization will be apparent in the later discussion. Related to these considerations is an observation already noted in the literature.KflThere are significant differences in the pH-rate profiles for the hydrolysis of aryl phosphates derived from phenols with pKa < 5.5 and with pKa> 5.5. Alkyl phosphates exhibit pH-rate profiles similar to those of the aryl phosphates derived from weakly acidic phenols (pKa> 5.5); these esters exhibit a maximum rate of hydrolysis at the pH which corresponds to a maximum concentration of monoanion. However, the maximum rate of hydrolysis of aryl phosphates that are derived from phenols with pKa < 5.5 occurs at the pH which corresponds to a maximum concentration of dianion. It should be noted that these differences in pH-rate profiles refer to hydrolysis of esters in aqueous solution. Medium effects in phosphoryl transfer are very important, and operate at two levels. (i) Aprotic solvents decrease acid strength relative to protic solvents; hence the medium controls the state of ionization of the phosphate and, thus, the relative concentrations of monoanion and dianion in the solution. (ii) Protic solvents participate in solvation of the ground state of monoanion and dianion to a much greater extent than they participate in solvation of those less polar transition states which result in the formation of phosphorane or metaphosphate ion intermediates. This preferential solvation of the ground state results in a significant decrease in rate when the aprotic solvent, e.g. acetonitrile, is replaced by a protic solvent, e.g. methanol or water. This effect is greater in the dianion than in the monoanion owing to the higher charge density of the dianion. An illustration of this effect is provided by phosphoryl transfer from 4-nitrophenyl phosphate. I n this system, the formation of metaphosphate is much faster from the dianion than from the monoanion in aprotic solvents and in alcohols. However, metaphosphate is generated at a much faster rate from monoanion than from dianion in water. This is attributable to greater solvation of the ground state of the dianion by water than of the ground state of the monoanion relative to the respective transition states which generate metaphosphate; the preferential solvation of the ground state the transition state by alcohols is not as strong as that of water, and cannot compensate for the greater tendency of dianion to generate metaphosphate when compared to monoanion. i p s .

146


These considerations apply also to phosphoryl transfer from ATP as described in another section. I t appears that the reactivity of ATP is intermediate between those of phenyl and 4-nitrophenyl phosphates. 2 Phosphoryl Transfer From Aryl Dihydrogen Phosphates The hydrolysis of phenyl (Ph), 4-nitrophenyl ( Ar’), and 2,4-dinitrophenyl (Ar’ ’) phosphates has been extensively investigated in aqueous solution in the pH range 0-14.5f-0 We have examined the more general problem of phosphoryl transfer from these aryl phosphates to alcohol and water in aprotic and mixed aprotic and protic media. Our study of the aryl phosphates involved an examination, using .IIP n.m.r., of six different systems, each system being in solution in anhydrous acetonitrile, in pure alcohols o r water, or in mixtures of acetonitrile with alcohols or water. These observations were supplemented by a study of the ‘H n.m.r. spectra of the solutions, and by the isolation and full characterization of compounds to which the n.m.r. signals were attributed. The reactions were carried out under comparable conditions of concentration ( 1 .O or 0.2 mol I - l ) and temperature (35 or 70°C). In all cases, approximate values of the reaction half-times ( 7 ) were estimated (-t 25 :$) from the times at which the ‘lP n.m.r. signal intensity of the reactant became equal to the signal intensity of the product. Values for these estimated half-times have been listed in previous papers.’ Only differences in r values by factors of three or higher are regarded as significant. The six systems included in this study are ( ( 1 ) the crystalline acid, XPO3H2, ( b ) the tetra-alkylammonium salt of the monoanion, XPO,H R,N ( R = Bu*lor Me), prepared in anhydrous form, (c) an equimolar mixture of the acid and a tertiary amine (XPO,H, + R3N 7: XP0,H- R,NH+), ( d ) the tetra-alkylammonium salt of the dianion, XPO,, 2RaN+, prepared from the reaction XP0,H- R 4 N t + R 4 N i O H - XPO,, 2R,N1 + H,O: since the stability of the dianion greatly decreases in the solvent series water > alcohols > acetonitrile, due to solvation effects discussed in a previous Section, we were able to study this system only with the mononitro-dianion salt, prepared as the monohydrate, ( e )an equimolar mixture of the tetra-alkylammonium salt of the monoanion and a tertiary amine (XP0,H- R , N + + R,N G XPO,,- R 4 N t R,NHi), (f’)a mixture of the acid and two mole equivalents of the amine (XPO,H, + 2R,N F~ XPOS2- 2R3NHf). Systems ( e ) and ( f ’ ) are equivalent in aqueous solution, but not in acetronitrile or alcohol solutions, owing to the enormous decrease in the acidity of oxygenated acids in aprotic solvents and in alcohols. Among carboxylic acids, the decrease in acidity in going from water to acetonitrile is larger among the weaker acids; e . g . , the corresponding pKa values of 3,5-dinitrobenzoic acid are 2.8 and 16.9 ( A p K a z 15), while those of acetic acid are 4.8 and 22.3 ( A p K a z 18). The same trends are noted among phenols ( ApKaz 12).* I f the effect of aprotic solvents o n acidity is analogous in phosphoric and carboxylic esters, it should be easier to study the behaviour of monoanions and dianions derived from phosphomonoesters in acetonitrile than in water. The decrease in acidity of aminium ions --f

J . F. Coetzee. Prog. Pf1.v.c..OrR. Cfirni.. 1967, 4, 45

Phosphoryl Transjkr from Phosphomorioestrrs arid Adtwosirre 5'- Triphosphatr 1 47 R R N H in going from water to acetonitrile ( ApKa 2 5- 7 ) is not nearly as large as i n the case of carboxylic acids and phenols.

Two types of amines were included in our studies: di-isopropylethylamine, Pri,EtN, as the prototype of a hindered non-nucleophilic amine, and quinuclidine, CH(CH,CH,),N, as an example of an unhindered nucleophilic amine. In aqueous solutions these two amines have very similar pK values. However, it appears that quinuclidine may be significantly more basic than Pri,EtN in acetonitrile solution. Utilizing this approach, it becomes apparent that the same aryl phosphate can react iiiu phosphorane or metaphosphate intermediates, depending on its state of ionization, and that different aryl phosphates can react ria phosphorane or metaphosphate intermediates although they arc in the same state of ionization. In general, the type of mechanism which operates in phosphoryl transfer depends on: ( a ) the structure of the phosphomonoester, ( h ) its state of ionization in a given solvent, ( c ) the nature of the solvent, and ( d ) the presence or absence of nucleoph i I ic ami nes. The following observations represent extreme examples where different mechanism types can be distinguished. (i) Phosphoryl transfer from the un-ionized dinitro- and mononitro-acids to alcohols is relatively slow, sensitive to the structure of the alcohol, and occurs at comparable rates when equimolar amounts of acid and alcohol are allowed to react in acetonitrile, o r when the acid is dissolved in excess of alcohol. Water behaves like methanol in this type of reaction.

The half-times for the formation of methyl phosphate from methanol, and of inorganic phosphate (Pi) from water, are 15 and 10 h, respectively, for the dinitroacid ( I M, in MeCN, at 35 C), and 6 and 4 days, respectively, for the mononitro-acid ( I M, in dioxan, at 70°C). These reactions, of which reaction ( 5 ) , for a mononitro-acid, is an example, are assumed to occur rici phosphorane intermediates. X

I

P--

HO/ \\o'OH

-

X

R0ti

Ho-p'

I ,,OH I 'OH

OR

(ii) Tetra-alkylammonium salts of the 4-nitrophenyl phosphate dianion can be readily prepared, and the behaviour of the dianion can be observed in acetonitrile solution. Phosphoryl transfers from the dianion to alcohols and water are extremely rapid, and proceed at comparable rates (t2 5 min in 1.OM solutions, at 35 "C). The rates of formation of methyl and t-butyl phosphates [reaction (6)] are virtually the same. These reactions are taken as representative of the eliminationaddition mechanism ciu monomeric metaphosphate, as shown in reactions (7) Ar'OP0;- + R 0 l i

( MeCN)

ROP0;-

+ Ar'OH

(6)

148

-

0

II

h'o-p-0I

Organophosphorus Chemistry PO; + Ar'O'

(7)

ROPO,H-

(8)

0PO; + ROH

--+

and (8). Of particular significance is the observation of a rapid formation of t-butyl phosphate when the reaction is carried out in the presence of ButOH. This is one of the criteria for the intervention of PO3-, since it seems unlikely that this alkyl phosphate can be formed ria a phosphorane intermediate under these conditions. As the aprotic solvent is replaced by alcohols or water in the reactions of the mononitro-dianion, reaction rates decrease in the sequence MeCN > ButOH > PriOH > MeOH > HzO. The formation of PO3- is faster from dianion than from monoanion in acetonitrile and alcohol solutions, but faster from monoanion than from dianion in aqueous solution. This phenomenon was discussed earlier as an example of differential solvation of the more polar ground state of the phosphate us. the less polar transition state for elimination by water us. acetonitrile or alcohol, and of the relatively greater solvation by water of the phosphate dianion us. the monoanion. (iii) The behaviour of the dinitro- and mononitro-monoanions Ar"OPO,H-and Ar'OP0,H- (as the Bun,N+ salts) can be contrasted to that of the respective acids Ar"OPO,H, and Ar'OPO,H, in aprotic media. In the dinitro-series, the monoanion and its acid form cyclic trimetaphosphate at comparable rates [reactions (10) and (9)]. However, in the mononitro-series, the monoanion forms trimetaphosphate at a much faster rate than the corresponding acid [reactions ( 1 2) and (1 l)].

3 Ar"0H

(9)

T(I.OM, at 35 "C) = 5 days 3Ar"OPO,H-

(MeCN) A

Ar'OPO,H, 3Ar'OPO,H-

(Me [Ar’’OP0,2-], and relative rate constants. As expected, there are no observable differences in the reactions of the dinitroacid and two mole equivalents of hindered and unhindered amine in pure methanol or water as solvent, presumably because in these protic media nearly complete ionization occurs to the dianion, which generates monomeric metaphosphate and the corresponding alkyl phosphate or Pi. The participation of nucleophilic catalysis is thus undetectable when the reaction is carried out in protic solvents such as water and methanol. 3 Does PO, Add to Non-enolized Ketones in Solution?

The fragmentation in alkaline solution of P-halogenophosphonic and &halogenophosphinic acids was originally discovered by Conant and ~ o - w o r k e r sand ,~ has been examined in greater detail by other investigators.1° This reaction has been observed with methyl hydrogen erythro- or threo-l-phenyl-l,2-dibromopropylphosphonate in the presence of base, and the formation of monomeric methyl metaphosphate as an intermediate has been postulated.ll More recently, this same reaction was carried out in the presence of an excess of acetophenone and afforded 1-phenylvinyl methylphosphate. It was suggested that this product resulted from a n attack by the methyl metaphosphate on the keto form rather than on the enol tautomer of acetophenone. A similar mechanism was proposed as a model for the enzymatic formation of phosphoenolpyruvate from pyruvate and ATP.12 The monomeric metaphosphate anion, rather than its alkyl metaphosphate derivative, would be the intermediate in an elimination-addition mechanism in !j

lo

11

I2

J . B. C o n a n t a n d A. A . Cook, J . A m . ChPm. Soc., 1920, 42, 830; J. B. C o n a n t a n d S. M. Pollack, ibid., 1921, 43, 1665; J . B. C o n a n t a n d E. L. Jackson, ihid., 1924, 46, 1003; J. B. C o n a n t a n d B. B. Coyne, ;hid., 1922, 44, 2530. J. A . M a y n a r d a n d J . M. Swan, Pruc. Chrm. Suc., 1963, 61; J. A. M a y n a r d a n d J . M. Swan, Aust. J. Chrni.. 1963, 16, 596: G . L. Kenyon a n d F. H. Westheirner, J. Ant. ChcJm. Soc., 1966, 88, 3357, 3361. A . C. Satterthwait a n d F. H. Westheimer,J. A m . Chem. Soc., 1978, 100, 3197. A . C. Satterthwait a n d F. H . Westheimer, J. A m . Chem. Soc., 1980, 102, 4464.

154


a biological phosphoryl transfer. We therefore investigated the reaction of acetophenone with the metaphosphate anion generated by our procedure in order to ascertain if this intermediate does indeed have the ability to produce an enol phosphate from a ketone. To generate the metaphosphate ion we resorted to the addition of two mole equivalents of the hindered amine Pri,EtN to 2,4-dinitrophenyl phosphate in acetonitrile solution. This reaction was carried out in the presence of one or more mole equivalents of acetophenone, and under these conditions we observed only cyclic trimetaphosphate as product. To exclude the possibility that the 1-phenylvinyl phosphate dianion, H,C-C(Ph)0POz2-, was indeed generated in this reaction, but decomposed too rapidly for detection, the vinyl phosphate was synthesized independently and its stability was studied under various conditions. Monoanilinium 1-phenylvinyl hydrogen phosphate was prepared as de~cribed,’~ and was converted into the bis(diisopropy1ethyl)ammonium salt. The rate of decomposition of this salt was negligible under the conditions which produce cyclic trimetaphosphate from the 2,4-dinitrophenyl phosphate dianion in the presence of acetophenone. The decomposition of the dinitro-dianion in the presence of an equimolar mixture of acetophenone and t-butyl alcohol gave t-butyl phosphate exclusively. We conclude, therefore, that the metaphosphate ion, PO3-, when generated in solution (at least under these conditions) is incapable of converting acetophenone into 1-phenylvinyl phosphate. Whatever the mechanism for the formation of 1phenylvinyl methylphosphate from the decomposition of methyl hydrogen eryrhro-1-phenyl-l,2-dibromopropylphosphonatein the presence of a hindered amine and acetophenone, this type of reaction is probably not a suitable model for the enzymatic transfer of phosphoryl to pyruvate or other carbonyl-containing biological substrates.

4 Mechanisms of Non-enzymatic Phosphoryl Transfer from ATP Several studies of the hydrolysis of ATP have appeared in the literature since 1953.14We have recently obtained pseudo-first-order rate constants from changes in ATP concentration measured by means of liquid chromatography.2 The hydrolysis was carried out at 70°C in a 0.01M aqueous solution of the salt ATPHZ2- 2Me,N+, at constant pH (in the range 0-10). In addition, we have determined the isotopic distribution in the inorganic phosphate (Pi) that is obtained when unlabelled ATP is allowed to undergo complete hydrolysis in water that is enriched with H2I8Oat various pH values. It is already known that the Pi obtained from the hydrolysis of ATP at pH 5.3, in the presence of Cu2+, 1:’

1 1

T . H a t a , K. Y a m a d a , T . Futatsugi, a n d M. Sekinc, Synthrsis, 1979, 189. K . L o h m a n n , Bioclii~t?~. 2.. 1932, 254, 381; A. Hock a n d G. Huber, ihicl., 1956, 328, 44; C. Liebecq a n d M. Jacqueniotte-Louis, Bull. Soc. Chiin. B i d . , 1958, 40,67, 759; D. Lipkin, R . Markharn, a n d W. H. Cook, J . An?. Chi,r7i. So(.., 1959. 81, 6075; S. L. Friess, ihitl.. 1953. 75, 323; M. T e t a s a n d J . M. Lowenstein, Bioc~hc,r~iisrrj~, 1963, 2, 350; P. W. Schneider a n d H. Brintzinger, Hclr. Chini. A(,ru. 1964, 47, 1717; D. H. Buisson a n d H . Sigel, Biochini. Bioph.\’.s.At.1~1,1974. 343, 45; M . M. T a q u i K h a n a n d M . Srinivas M o h a n , J. Inorg. N u t , / . C ‘ h ~ r ~ i . 1974, , 36, 707; M. M. T a q u i K h a n a n d M . Srinivas M o h a n , inclitrri J. Cliv111.. Src t . A , 1976, 14, 945, 951; P. E. Arnsler, D. H. Buisson, a n d H. Sigel, Z.Nutitr$w.sc//., T ~ i l C, . 1974. 29, 680; H . Sigel, D. H . Huisson. a n d B. Pris, Biainorg. C ’ h c ~ ~ t 1975, ~ . , 5, I ; P. E. Anisler a n d H. Sigel. Eur. J. Bioch~rti..1976. 63, 569; H . Sigel a n d P. E. Anisler. J. Atti. Clicm. Soc.. 1976, 98, 7390.

Phosphoryl Transfer from Phosphomonoesters atid Adenosine 5'- Triphosphare 1 5 5

contains one oxygen atom from the water.15 In our studies, Pi was isolated by standard procedures, and was converted into H,PO, and (MeO),PO for isotopic analysis by mass spectrometry. In principle, the hydrolytic cleavage of ATP can proceed as follows: H ~ O+ A T P ( P ~ )

H,O + A T P ( P Q ) H,O +

ATP(PP)

-

-

-+++

ADP + pi

(22)

PPi + AMP

(23)

pi + ADP

(24

2 Pi

(27)

Further hydrolysis takes place as follows:

H,O + PPi

We find that, in l.OM-HCI, water attacks almost exclusively at the PY atom of ATP. All the Pi that is obtained after complete hydrolysis to AMP+ 2Pi contains only one oxygen atom from the water.Is I f cleavage had occurred at Pa and Pa, there should have been some Pi with no oxygen and some with two oxygen atoms from the water. Further studies with [y-l8a]ATP containing 96.0 atom 7; la. have revealed that the hydrolysis of ATP in ].OM-HCI involves 92-9376 attack by water at the Pr atom and 8-7",< attack at the Pfl atom. Attack at the Pa atom produces Pi and ADP. When the changes in ATP, ADP, and AMP concentrations with time in the hydrolysis of ATP in IM-HCI are plotted, one obtains curves of the type expected if k , z k , in the sequence: ATP

H,O tl 0 7 ADP 7 AMP I

If the hydrolysis is performed in 0.1 M-HCI, the hydrolysis of ATP is faster than that of ADP by a factor of about 4. The hydrolysis of ATP is faster in IM-HCI than at pH 9.30 by a factor of 4200 ( 104k= 1390 us. 0.33 min-I). The rate levels off above pH 9.3. The pH-rate profile reaches an approximate plateau between pH 4.0 and 7.0 ( 104k= 7.13 and 5.1 1 min l , at pH 3.98 and 6.69 respectively). Under the conditions of the hydrolysis, the pKa3 of the dianion ATPHZ2-and the pKa4 of the trianion ATPH3- are 4.3 and 7.32, respectively, with the initial pKa1 and pKa2 values being lower than 1.5. Hence, the acid ATPHl and the monoanion ATPH,- are the only species that are expected in significant amounts at pH < 2. I n the pH range 2-6, various mixtures of monoanion, dianion, and trianion are present. Only trianion and tetra-anion are expected in the pH range 6-9, with virtually pure tetra-anion present at pH > 9.

-

-

I5

11. Moll, P. W. Schneider. and H. Brintzinger. H c l r . Chim. Alrci, 1964, 47, 1837

I 6

F. Kaniirez, J . F. Marecek. S. Meyerson, and E. K u h n . unpublished work.

156


It should be noted that the pKa3 value of 4.3 refers to the equilibrium involving the basic adenine ring and its protonated form. However, changes in conformation of the polyphosphate chain and the adenosine moiety can occur in solution as a result of electrostatic attraction between the positively charged adenine and the polyphosphate oxyanion. This effect allows for an intramolecular proton transfer between the PY oxyanion and the protonated adenine, which in essence constitutes intramolecular acid catalysis during the addition of nucleophiles to the PY atom. On the basis of our studies, and by analogy with the results obtained with aryl phosphomonoesters,' we interpret the pH-rate profile for the hydrolysis of ATP as follows. The hydrolyses of the acid ATPHl and of the monoanion ATPH; occur by an addition-elimination mechanism ciu a phosphorane intermediate (Scheme 5). The tetra-anion and the trianion have a terminal PY group of the 0

II Ado-P-O I OH

0

0

II I1 -P--0-P-OH 1 I OH OH

0

0

I

I/ 2 Ado-P-0--P., H,O

I

I

0

II I OH

It

AdO- -P-0-P-OH

''0

I 1

OH ,,OH H 0 -- P' 'OH

OH

OH 0

II I OH

+ H,PO,

Scheme 5 0

0

II II Ado-P-0-P-0-P-0I I

0

II

I

0-

0-

0-

0-

0-

0-

_+

0

0

0-

I 0-

II Ado-P-0-P-0I

0-

II

OH

i Scheme 6

+ PO;

0'

Phosphoryl Transfer from Phosphomonoesters and Adenosine 5'- Triphosphate 1 5 7

type XP032-and XP03H-, respectively, and undergo hydrolytic cleavage at that group by an elimination-addition mechanism via the rnetaphosphate ion. The trianion generates metaphosphate faster than the tetra-anion by a factor of about 18 (see Scheme 6). The highly electrophilic metaphosphate ion reacts rapidly with the nucleophile to yield the product: ROH+PO,ROP0,H-. The proton-shift that is assumed to occur in the trianion allows the elimination of the anion, rather than of its conjugate acid PO,H, as was discussed in a previous section . The metaphosphate mechanism for the hydrolysis of the tetra-anion and trianion of ATP has already been suggested.'' We have added support for this hypothesis by the following observations. t-Butyl phosphate is formed when solutions of tetra-n-butylammonium salts of these anions in mixtures of acetonitrile and t-butyl alcohol are kept for several hours at 70°C: ATPATPH"-

+

Me3COH

+ Me3COH

--+Me3COP03z- + ADPH2Me3COP03H-

+ ADPH2-

(28)

(29)

It is unlikely that t-butyl phosphate can be derived from any reaction other than the entrapment of the highly reactive metaphosphate intermediate. The rate of decrease of ATP concentration is insensitive to the structure of the alcohol, and isopropyl alcohol yields isopropyl phosphate at a comparable rate. Our experiments have not resolved the question of whether the dianion ATPH 22- reacts via metaphosphate or oiu phosphorane intermediates. It is probable that both mechanisms are competitive in this species. In solution, the shifts of protons to and from the oxyanions of the PY group, which appear to be needed for the formation of phosphorane and metaphosphate intermediates, respectively, can occur rapidly. From observations made among aryl phosphomonoesters, it appears that a phosphate group with one or two protons, i.e. XP03H- or XP03H2,is able to generate a phosphorane, while the doubly charged phosphate prefers to generate a metaphosphate. We speculate that, in the active site of an enzyme, protonation is specifically directed toward a particular oxyanion. Therefore, a tetra-anion (ATP-) that is bound to the active site will be protonated at one of the two PY oxyanions, forming the trianion ATPH3-, which may not be able to undergo the proton shift that is required for generation of metaphosphate. The implication is that the ATP trianion ATPH3-, which in solution reacts via metaphosphate, may react via phosphorane in the active site of an enzyme. The rates of hydrolysis of the complexes MgATPH2 and CaATPH, have also been studied at constant pH, in the range 1.5-8.2, utilizing buffers which do not appreciably affect these complexes. We find that the Mg2+and Ca2+ions have little or no effect on the rate of formation of metaphosphate from the trianion. However, Mg2+and Ca2+increase the rate of formation of metaphosphate from the tetra-anion by factors of about 10 and 50, respectively. As expected, rates of hydrolysis at pH c 3 are similar in the presence and in the absence of the two metal ions. We account for these results as follows. I i

D. L. Miller arid F. H. Westheimer. J . A m . C/iom. Soc., 1966, 88, 1507.

6*

158

Organophosphorus Chemistry 0 Ado-P

I

O,

0

I

0 Ado-

I

/o

0-

Mg

0

0

0

II II P-0-P"

0

0'

,0 MI2

I

I

O,

II I

\ P-

0-

(2)

(1)

(3)

(4)

Recent studies of the 31Pn.m.r. chemical shifts of the salt ATPH,? 2Me,N and the complex MgATPH, in 0.02M-D20 solutions at p D 8.20, 6.20, and 3.70, and comparison of the results with those obtained from solutions of ADPH2 At p D 8.20, 2Me,N+ and MgADPH, have led to the following three bidentate complexes (1)-(3) are in equilibrium with each other, and this equilibrium is relatively rapid on the time-scale of n.m.r. at 22°C. The changes in conformation of the polyphosphate chain as the various oxyanions become electrostatically bound to the bivalent cation cause the changes that are observed in the chemical shifts of the three nuclei. The effect of magnesium on the signals does not specify the position of the metal in the chain. Calcium has virtually the same effect as magnesium on the three signals of ATP, under the same conditions. The formation of metaphosphate and of MgADP- (4) is faster from one of these complexes, since the bivalent cation renders ADP3- more nucleofugic by neutralizing two of the negative charges, as shown in reaction (30). The magnesium 1

0

0

0

II

complex of the trianion, MgATPH-, generates metaphosphate at about the same rate as the metal-free trianion, ATPH". This is expected from the observed effects of magnesium ions on 31Pn.m.r. signals of ATP at various pH values. One can say that protonation at PY weakens the binding of magnesium to the polyphosphate chain and hence disfavours the nucleofugacity of MgADPH, or that the (MgP"PP)ATPH- complex disfavours the proton shift that is needed for metaphosphate formation. In the above hypothesis, CaADP- is a better nucleofugic group than MgADP during the formation of PO,- from the corresponding complexes CaATP2- and F. Raniirez and J . F. Marecek. Biochim. B i o p h i ~ .Acta, 1980. 589, 21

Phosphoryl Transfer from Phosphornonoesters arid Adenosine 5’-Triphosphate 1 5 9

MgATP2-, presumably due to tighter binding of Ca2’ than Mg2+to the pyrophosphate oxyanions. The addition of imidazole, pyridine, or quinuclidine (up t o 50 mole equivalents) does not have a significant effect on the rate of hydrolysis of A T P - . In summary, the non-enzymatic behaviour of ATP in solution, including the effect of Mg2+and Ca2+ions, is reasonably well understood. However, the situation which results when MgATP binds to an enzyme is quite complicated. One aspect of this problem is discussed in the next Section. 5 Enzymatic Hydrolysis of ATP : Actomyosin MgATPase

in Muscle Contraction Muscle contraction is basically a two-stage process in which the hydrolysis of MgATP, catalysed by myosin, releases energy; this is coupled to contraction by interactions between myosin and the protein actin. Actin activates the release of Pi from a myosin-ADP-Mg-Pi complex t o the medium after the cleavage of ATP. In the absence of actin, the Pi-release step, not the cleavage, is rate-limiting in the MgATPase pathway. During the hydrolysis of MgATP by myosin or its enzymatically active subfragments, there is an exchange between water and the terminal PY group of the enzyme-bound nucleotide. Ultimately, the PY group appears in the Pi that is released from the enzyme to the medium. This exchange has been called ‘the intermediate oxygen exchange’ in myosin ATPase, and much effort has been devoted to the elucidation of the mechanism by which it occurs.1e In a recent study20 in which the myosin-catalysed hydrolysis of Mg[p1*O1ATP was carried out in the presence of actin, an interesting pattern was obtained for the incorporation of oxygen from H 2 0 of the medium into the Pi that was formed in the hydrolysis. (The distribution of [“.n]Pi species in the Pi that was produced by myosin-CaATPase, which is known not to cause ‘intermediate oxygen exchange’, was used to define the isotopic distribution in the original [.J)-’~O.]ATP. This allowed the calculation of each [InOn]Pispecies in the Pi that was produced by myosin-MgATPase. The values tz = 3, 2 , I , and 0 correspond to none, one, two, and three ‘intermediate oxygen exchanges’, respectively.) When the enzyme was the native myosin obtained from rabbit skeletal muscle, the Pi that was formed consisted of four species: H,P.,O(no exchange; 27-38 :)-dATP[zS]is polymerized in the presence of poly(dT) .oligo(dA) template primer, the product that is formed is digested by snake venom phosphodiesterase at a similar rate to that of (Rp)-poly(;A) [i.c.. poly(A) that contains internucleotidic links of (Rp)-thiophosphate], indicating that polymerization proceeds stereospecifically with inversion to yield (R~)-poly[d(sA)],probably riu an in-line mechanism.Yu The stereochemical course of activation of amino-acids by methionyl- and tyrosyl-tRNA synthetases has been in~estigated.~' When each ~-['~O,]aminoacid is incubated with (SP)-ATP[~S] (41) and the appropriate aminoacyl-tRNA synthetase, the corresponding aminoacyl thioadenylate is formed, which on treatment with hydroxylamine yields the aminoacyl hydroxamate and (66) if the synthetase reaction involves inversion at phosphorus, and (65) if it involves retention. The nucleotide product is phosphorylated on the pro- R oxygen, as before, with adenylate kinase and pyruvate kinase, and the 31Pn.m.r. spectrum of the resulting ATP[aS] shows that (42) is formed, with l*O in the non-bridge position. Hence (66) was formed viu inversion at phosphorus, probably viu an in-line mechanism. The same result was obtained for both aminoacyl synthetases. The reaction pathway of valyl-tRNA synthetase from E. coli has also been investigated, using b- and ;I-thio-analogues of ATP.92While ATP[yS] promotes both aminoacylation and pyrophosphate-exchange reactions with similar efficiency to ATP, the (Rp)-isomer of ATP[/jS] is preferred to the (Sp)-isomer for the overall aminoacylation reaction, but the (Sp)-isomer is preferred for the exchange reaction. I t appears that, in the absence of pyrophosphate, the enzyme catalyses a novel interchange reaction in which ATP[yS] is formed from (SP)ATP[PS] with high stereoselectivity. I t has been observed that the equilibrium constant of the reaction that is catalysed by 3-phosphoglycerate kinase is shifted towards the 3-phosphoglyceroyl phosphate side by a factor of 10 when ATP[PS] is employed as substrate in place of ATP.g" Metal complexes of the diastereoisomers of ADP[aS] have been investigated as inhibitors of myosin ATPase, and both (Rp)- and (Sp)-isomers were found to be effective inhibitors, irrespective of whether Mg2' or Co2' is present, suggesting that the metal ion is not co-ordinated to the a-phosphorus in the enzyme-ADP complexB4( c f . ref. 90).Moreover, the /)-unidentate CrIII-ADP complex is a much more powerful inhibitor than the afi-bidentate CrlIr-ADP complex, suggesting that, as with yeast hexokina~e,'~ the 8-unidentate metal-ADP complex is the product of myosin A T P ~ S ~ . ~ ~ Studies similar to those detailed above have been described for a number of other enzymes. Carbamate kinase uses the Mg2' salt of (Rp)-ATP[PS] as substrate, and this stereospecificity is not reversed by Cd". The enzyme accepts both ( R P ) - and (Sp)-isomers of ADP[aS] with Mg2+ and Cd2+. Carbamoyl phosphate synthetase requires specifically the (Sp)-isomer of ATP[PS] (69) in the presence of Mg2 and the (Rp)-isomer in the presence of Cd2+(72), and this and +

P. M . J. Burgers and F. Eckstein, J . B i d . Chem., 1979, 254, 6889. L)lS. P. Langdon and G . Lowe, Nature (London), 1979, 281, 320. 9 2 E. F. Rossomando, L. T. Smith, and M . Cohn, Biochemistry, 1979, 18, 5670. y3 E. K . Jaffe and M . Cohn, J . Biol. Chrm.. 1980,255, 3240. D. Yee and F. Eckstein, FEBSLrtt., 1980, 112, 10.

Nucleotides and Nucleic Acids

?

185 X

(69) M = Mg,X = S , Y = 0

(70) M = Co, X = S,Y = 0 (71) M = C o , X = 0,Y = S (72) M = Cd, X = 0,Y = S

other evidence indicates that the A configuration of the chelate ring is recognized by the enzyme. Conversely, glutamine synthetase appears to recognize the A configuration of the ring. 9 5 DNA-Dependent RNA polymerase can employ diastereoisomers of ATP[aS] and ATP[BS] in place of ATP in the initiation reaction, the (Sp)-diastereoisomers being preferred to the ( RP) ones. The diastereoisomers of Up(S)A can replace UpA in the primed initiation reaction, the ( R P ) isomer being preferred to the (Sp)-isomer. Both initiation and primed initiation reactions employing ATP and (Sr)-UTP[aS] in the presence of T7 DNA proceed with inversion of configuration at phosphorus on forming the inter-nucleotide link. The pyrophosphate-exchange reaction into (Sp)-UTP[aS], catalysed by the enzyme in the presence of CpA and T7 DNA template, proceeds with retention of c o n f i g u r a t i ~ n Both . ~ ~ (Sp)-ATP[aS] and (Sp)-UTP[aS] are substrates for the elongation reaction of the enzyme in the presence of Mg2+,the (Rp)-isomers being weak inhibitors. With Mg2+,both (RP)- and (Sp)-ATP[BS] are substrates, while with Cd2 only the (Rp)-isomer (72) is a substrate. These findings have led to the proposal that the A-isomer of MgATP is the form that is active with RNA polymerase, and a model for the binding of the substrate to the active site has been proposed.97Both ( R P ) -and (Sp)-ATP[PS] may be used as donor substrates by cA M P-dependent protein kinase from bovine cardiac muscle. In the presence of Mg2+,the (Sp)-isomer (69) is preferred, while the (Rp)-isomer (72) is preferred in the presence of Cd2+.It has therefore been postulated that the A-isomer of the metal-nucleotide chelate is recognized preferentially.g8 Methods for the synthesis of the ( R p ) - and (Sp)-isomers of [y-32P]ATP[BS] have been detailed.99The (Rp)-diastereoisomer is readily prepared by stereospecific transfer of the labelled phosphate group from acetyl [32P]phosphateto ADP[PS], using acetate kinase. For the (Sp)-diastereoisomer, H,32P04 is incubated with NAD+, glyceraldehyde 3-phosphate, and glyceraldehyde 3-phosphate dehydrogenase to afford 3-pho~phoglyceroyl-[~ *P]phosphate, from which the labelled phosphoryl group is transferred stereospecifically to ADP[PS] in the presence of 3-phosphoglycerate kinase, affording the required compound. If the labelled orthophosphate in this latter procedure is replaced by 36S-labelled thiophosphate, [35S]ATP[yS]of high activity may be prepared, in fair yield.'OO +

R . P. Pillai, F. M . Raushel, and J. J . Villafranca, Arch. Biochem. Biophys.,1980. 199, 7. D. Yee, V. W. Armstrong, and F. Eckstein, BiochPrnistr.v, 1979, 18, 4116. 97 V. W. Armstrong, D. Yee, and F. Eckstein, Biochemistrjp, 1979, 18, 4120. 98 D. W. Bolen, J. Stingelin, H. N. Bramson, and E. T. Kaiser, Biochemistry, 1980, 19, 1 1 76. 9 9 J. Stingelin. D. W. Bolen, and E. T. Kaiser, J . Biol. Chrm.. 1980, 255, 2022. l o o P. S. Cassidy and W. G . L. Kerrick, Biochim. Biophivs. Acta, 1979, 565, 209. 95

96

186

Organophosphorus Chemistrjt

When nucleosides are heated, dry, with a mixture of urea and [32P]orthophosphate at 1 0 0 “C,a mixture of the labelled nucleoside 2‘-, 3‘-, and 5‘-monophosphates is formed. These may be separated chromatographically, and the 5’-isomers converted into the corresponding triphosphates, using pyruvate kinase, nucleotide kinase, and appropriate substrates. Nucleoside [a-32P]triphosphatesof very high specific activity may be obtained in this way.l0’ Novel phosphonate analogues of dTDP and dTTP have been described.lo2 Treatment of 5’-O-tosyl-2’-deoxythymidinein DMF with the appropriate phosphonic acid in the presence of a lipophilic base affords (73)-(75) in moderate yields. The position of the nucleoside was confirmed in each case by n.1n.r. spectroscopy, and the stereoisomers of (74) were separable by h.p.1.c. 0

II R1-P-CH I

R‘O

0

II

*-P-OdThdJ’

I

R’O

(73) R’ = OH, R’ = H (74) R‘ = EtO, R’ = Et (75) R 1 = CH,P(O)(OH),, R2 = H

An enzyme, ATP :nucleotide pyrophosphokinase, which catalyses the efficient transfer of the 5’-/j;~-pyrophosphoryIgroup of d ATP to the 3’-hydroxy-group of the four common deoxynucleoside 5’-triphosphates at pH 9 in the presence of Co2+,has been isolated from Streptomyces udephosphoi-vticus. Yields of the deoxynucleoside 5’-triphosphate 3’-diphosphate products are moderate to good. 3’-O-Methyl-2’-deoxynucleoside5’-triphosphates have been obtained directly, in good yields, by methylation of the corresponding triphosphates with dimethyl phosphate in concentrated alkali. l o 4 3‘-Deoxyadenosine 5’4riphosphate is a chain-terminator substrate for RNA polymerases, and consequently the incorporation of radiolabel from 3’-deoxyadenosine 5’-[a-32P]triphosphate at RNA chain termini may be used to determine the number of RNA chains being propagated in transcription systems in vitro.lo5 2’,3’-Dideoxythymidine 5’-triphosphate, which is a poor inhibitor of DNA polymerase o! from mouse myeloma in the presence of Mg2+,becomes a powerful competitive inhibitor with respect to dTTP in the presence of Mn2+.lo6It is not clear whether interaction of M n 2 + with the substrate, the enzyme, or the template is the critical parameter. Fluorescent nucleotide analogues are valuable for binding and kinetic studies in those enzymes that will accept them as substrates or inhibitors. Treatment of nucleoside or of deoxynucleoside 5’-triphosphates with 1-aminonaphthalene-4sulphonic acid and a water-soluble carbodi-imide in aqueous solution affords the C. K. Biebricher, Anal. Biorhcm., 1979, 95, 419. J . A. Stock, J . Org. Chcm., 1979, 44. 3997. J-I. Mukai, A. Razzaque, Y . Hanada, S. Murao, arid T. Nishino, Anal. B i o d w t ~ r . ,1980, 104, 136. l o ’ L. A. Voznyuk, A. M . Kritzyn, and V. L . Florentiev, Bioorg. Khint., 1980, 6, 205 ( C h e m . Abstr., 1980, 92, 198 684). 1°5 N. Olszewski and T. J . Guilfoyle, Biochc~tir.Biophys. Res. Commun., 1980, 94, 553. loH K . Ono. M . Ogasawara, and A. Matsukage, Biochrm. Biophjps. Reg. Commlm.. 1979, 88, 1255.

lo’

103

Nuc1cotidt.s and Nucleic Acidr

187

0 NH-P

0,s

0

II I

0

I1 0-P--0-

-P

-0

-0

-0

I1 I

~

O

HOv

R B

(76) R = OH; B = Ade-9, Gua-9, Ura-I, or Cyt-1 (77) R = H ; B = Ade-9, Gua-9, Thy-I, or Cyt-1

(78) X = NH, (79) X = H (80)X=OH

1

I

R = I-ribofuranosyl

fluorescent ;~-(4-sulphonaphthylamido)-analogues (76) and (77) in fair yields. lo’ Cleavage of the a-/j phosphate bridge results in changes in the absorption and emission spectra, particularly in the pyrimidine derivatives, and the analogues may be used to study the formation of phosphodiester bonds by RNA polymerase from E. coli, l o * The fluorescent ‘stretched’ nucleoside analogues linbenzoguanosine (78), /in-benzoinosine (79), and liwbenzoxanthosine (80) have been prepared, and phosphorylated using pyrophosphoryl chloride in rn-cresol to afford the 5’-monophosphates, and thence the 5’-phosphoromorpholidates, to give the 5’-diphosphates. The corresponding 5‘-triphosphates were obtained from the diphosphates, using phosphoenolpyruvate and pyruvate kinase, in high yield. Derivatives of (78) and (80) are very strongly fluorescent, those of (79) being less so. The 5’-diphosphate of (79) is a substrate for polynucleotide phosphorylase from Micrococcus lutru.~,affording poly(lirr-benzoinosinic acid).l o o The closely related P ‘-(lin-benzo-5’-adenosyl)-P4-( 5’-adenosyl) tetraphosphate and -P5-(5’-adenosyl) pentaphosphate, prepared from lirr-benzoadenosine 5‘phosphoromorpholidate, using ATP and p,A respectively, are powerful inhibitors of adenylate kinase from pig muscle. l o Diri bonucleoside monophosphates containing fluorescent 3’-termini have been prepared by treating guanosine 2’,3’-monophosphate with I ,N6-ethenoadenosine2-sulphonate and 1 ,NG-etheno2-aza-adenosine 2’(3’)-monophosphate, respectively, in the presence of ribonuclease N,.”’ Solubility considerations dictated the use of the 2’(3’)-phosphate for the latter synthesis. I t is proposed to use these compounds to follow kinetics o f action of nucleases. The 5‘-triphosphate of ribavirin [the nucleoside moiety of (14)]has been shown to be a powerful competitive inhibitor of the ‘capping’ guanylation of viral ‘07

loH lo!l ll(J

L . R. Yarbrough, J . G . Schlageck, and M. Baughman, J . Biol. Cheni., 1979, 254, 12 069. J . Ci. Schlageck, M . Baughman, and L. R . Yarbrough, J . Biol. Cfirni., 1979,254. 12 074. N . J . Leonard and G. E. Keyser, Proc. NorI. A c d . Sci. USA, 1979, 76. 4261. 1’. VanDerLijn, J . R . Barrio. and N . J . Leonard, Biocfrc~nii.srr~~, 1979. 18. 5557. K . C . Tsou and K. F. Yip, Nuclrir Acids Res., 1980, 8, 567.

188


m R N A in a vaccinia virus system.112I t is noteworthy that ribavirin is ineffective against poliovirus in which the mRNA lacks the ‘cap’ structure. I n a most unusual reaction, it has been shown that the action of ribonucleoside diphosphate reductase on its inhibitor 2’-chloro-2’-deoxyuridine5’-diphosphate results in the release of chloride ion, uracil, and pyrophosphate.l13 The sugar remnant has not been identified, but, although the mechanism remains unclear, it has been suggested that formation of a 3’-ketonucleotide as the first step could account for these findings. A number of analogues of dTTP, derived cia nucleophilic displacement of iodine in 5-iodo-dU MP and subsequent conversion into the triphosphate, have been investigated as inhibitors of hamster cytoplasmic thymidine kinase, with a view to establishing bulk tolerance at C-5 for the dTTP-binding site.l14 Similar studies have been performed on adenylate kinases, using N 6 - and 8-substituted ATP derivatives to establish differences in substituent tolerance between species and i s o ~ y m e s Base-modified .~~~ analogues of ADP have been examined as possible substrates for photophosphorylation. l 6 8-Bromo-ADP proved a poor substrate, suggesting that an unti, gauche-guuche conformation may need to be recognized for substrate binding, and the C(6)-N( 1)-C(2) region of the heterocycle also seems critical in determining binding. 3’-O-Acylated derivatives of ADP have been prepared by treatment of ADP with the appropriate acylimidazolides, and shown to be powerful and specific inhibitors of oxidative phosphorylation in beef heart mitochondria. l 7 The hydrophobic 3’-substituent is thought to fit into a hydrophobic cleft on the enzyme which is only exposed in the energized state. Analogues of ATP have been used to investigate the substrate specificity of the ATP-pyrophosphate exchange reaction of aminoacyl-tRNA synthetases, which was shown to be less stringent than that of the aminoacylation reaction.’ l 8 A study of a series of 5-alkyl-2’-deoxyuridine5’-triphosphates as substrates for mammalian and bacterial DNA polymerases has also been reported. l 9

Affinity Labelling.-While reagents for affinity labelling continue to be used widely, little novelty in the design of new reagents for this purpose has been reported. Among reagents of established value, 8-azidoadenosine 3’,5’-monophosphate has been used for photoaffinity labelling of the CAMP-receptor protein of E. colileOand, it appears, CAMP phosphodiesterase in Dictyostelium discoideum ghost membranes. l 2 8-Azidoadenosine 5’-monophosphate has also been used for this latter purpose,lZ1 and also for photoinactivation of the methotrexate-transport system in L1210 cells.1228-Azido-1,W-etheno-ATP has 113 114 115

IL6 ‘17

L1*

121

122

B. B. Goswami, E. Borek, 0. K. Sharma. J . Fujitaki, and R . A . Smith, Eiochenz. Eiophy.~. Res. Commun., 1979, 89, 830. J . Stubbe and J . W . Kozarich, J . A m . C h ~ mSoc., . 1980, 102, 2505. A . Hampton, F. Kappler, and R . R . Chawla, J . Med. Chem., 1979, 22, 621. A. Hampton and D. Picker, J . Med. Cham., 1979, 22, 1529. E. Schlimme, E. J. de Groot, H. Strotmann, and K. Edelman. FEES L e t t . , 1979, 106, 251. G . Schafer and G. Onur, Eur. J . Eiocheni., 1979, 97, 415. W. Freist and F. Cramer. Eur. J . Eiorhem., 1980, 107, 47. J . Sagi, R . Nowak. B. Zmudzka, A . Szemzii. and L. Otvos, Eiochim. Biophys. Acta, 1980, 606, 196. H. Aiba and J . S . Krakow, Biochemistr)., 1980, 19, 1857. L. J . Wallace and W. A. Frazier, J . Biol. Chenz., 1979, 254, 10 109. G . B. Henderson, E. M . Zevely, and F. M. Huennekens, J . Biol. Chem., 1979, 254, 9973.

Nuckorides and Nucleic Aidx

189

C-0 (81) R’ = 4-N3C,H4CH,, R2 = H, n = 2, NUC= Guo-5’ (82) R’ = 4-N3C,H4, R2= H , n = 2, N U C= Ado-5‘ (83) R‘ = 4-N3C6H4,R2 = H, n = 1, NUC= GUO-5’ (84) R’ = 4-N3C,H4CH2,R2 = Me, n = 2, Nuc = Ado-5’

I I

(CH,),

NH

I

pJN02 N3

(85)

been employed for the fluorescent photoaffinity labelling of F1 ATPase from Micvococcus luteus, in which the label becomes bound preferentially to the /3-subunit of the enzyme,123and 8-azido-GDP and 8-azido-GTP have been used to probe aspects of the GTPase-linked mechanism of polymerization of tubulin.lZ4 Treatment of GTP with 4-azidobenzylamine in the presence of DCC affords (81), which has been used in photoaffinity-labelling studies of RNA polymerase from E. coli, along with guanosine 5’-(3-azidotriphosphate). 125 The closely related adenosine 5’-[3-(4-azidoanilido)triphosphate] (82) has been employed for the photoaffinity labelling of arginine kinase and creatine kinase,126and studies on the modification of phenylalanyl-t RNA synthetase from E. coli MRE600 on irradiation in the presence of (83) and (84) suggest that effector sites on the enzyme are becoming labelled.127The photoaffinity label and ATP analogue 3’-0-{3-[N-(4-azido-2-nitrophenyl)amino]propionyl}-ATP (85) specifically antagonizes ATP-induced contractions of the vas deferens of the guinea-pig, and this antagonism becomes irreversible on irradiation, providing evidence for the existence of purinergic receptors which use ATP as the neurotransmitter.12s In other photoaffinity-labelling studies the tRNA molecule itself has been employed as the photosensitive reagent. Irradiation of ternary complexes of 70s ribosomes from E. coli with poly(U) and either phenylalanyl-tRNAPhc or N-acetylphenylalanyl-tRNAPhe results in cross-linking, permitting the identification of the ribosomal proteins that interact with tRNA in the A- and P-sites, respectively.129 An extensive study of the cross-linking of tRNAPhe to yeast phenylalanyl-tRNA synthetase by irradiation at specific wavelengths, so as to excite different chromophores in the molecule (wybutine, 31 5 nm; 4-thiouridine, 335 nm), and also following oxidation of the 3’-terminus with periodate, has 123 124 125

127 12R 128

H-J. Schafer, P. Scheurich, G. Rathgeber, and K . Dose, Anal. Biochem., 1980, 104. 106. R. L. Geahlen and B. E. Haley, J . Biol. Cheni., 1979, 254, 1 1 982. E. D. Sverdlov, S. A. Tsarev, and N . F. Kuznetsova, FEBS Lett., 1980, 112, 296. P. Vandest, J-P. Labbe, and R. Kassab. Eur. J . Biochem., 1980, 104, 433. 0. I . Lavrik and G. A . Nevinsky, FEBS Lett., 1980, 109, 13. G. K. Hogaboom, J . P. O’Donnell, and J. S. Fedan, Science, 1980, 208, 1273. G. G. Abdurashidova, M . F. Turchinsky, Kh. A . Aslanov, and E. I . Budowsky. N i d e i c Acids Res., 1979, 6, 3891.

7*

190


been described.’:jO Periodate-oxidized tKNAf-\*’treacts with methionyl-tKNA synthetase from E. coli, and, following reduction by sodium cyanohydridoborate, an inactive I : I covalent complex is obtained.’.” Periodate-oxidized adenosine nucleotides “” have again found use, with the labelling of F, ATPase by treatment with periodate-oxidized ADP and subsequent reduction with borohydride serving to indicate that the non-catalytic nucleotide-binding site of the enryme is localized on the r-subunit(sj.1;i:3 Treatment of 3’-amino-3’-deoxyadenosine 5’-triphosphate (86) with the bromoacetyl ester of N-hydroxysuccinimide affords (87), and treatment of 3’amino-2’,3’-dideoxyadenosine 5’-triphosphate with thiocarbonyldi-imidazole affords (88). As noted previously,1o5nucleoside triphosphates that are modified at the 3’-hydroxy-group are chain terminators for RNA polymerase, forming inactive ternary complexes with the enzyme in the presence of poly(dT) and oligo(Aj. When RNA polymerase is incubated with poly(dT), [5’-:’2P](pA),,, and (87), (88), or (86) (using glyoxal to cross-link the terminator to the enzyme in the last instance), RNA polymerase becomes labelled on the /I’-subunit in each case, indicating that this subunit contains the 3’-terminus of the nascent RNA chain i n the ternary complex. BrCH,CONH ~

0

0

o - ~ - o - p II-0

0-”rd-5’

I

-0

(86) K’= NH,, R2 = OH (87) R’= NHCOCH,Br, R’ = OH (88) R’ = NCS, R’ = H

If uridine 5’-phosphoromorpholidate is treated with 4-nitrophenyl phosphate, to afford P ‘-(4-nitrophenyl) P 2-(5’-uridyl)pyrophosphate, and this is catalytically reduced and then acylated, using the bromoacetyl ester of N-hydroxysuccinimide, (89) is obtained. Compound (89) is an active-site-directed irreversible inhibitor of UDP-galactose 4-epimerase from E. coli, the rate of inactivation of the enzyme correlating with the rate of covalent incorporation of one molecule of (89) at the active I t appears that the tightly bound molecule of N A D + that is associated with the enzyme becomes alkylated in the adenine ring by (89), and is rendered irreducible.lRB 4 Oligo- and Poly-nucleotides

Chemical Synthesis.-A published. I R 7 130 131

132 133 *34 135

l:I6

L37

new review o n the synthesis of polynucleotides has been

M. Baltzinger, F . Fasiolo, and P. Remy, Eur. J . Biochem., 1979, 97, 481. C. Hountondji, G . Fayat, and S. Blanquet, Eiir. J . Biochern., 1979, 102, 247. P. N . Lowe, H . Baum, and R . B. Beechey, Biochrtn. SOC.Trans.. 1979, 7 , 1 I 3 I . I. A . Kozlov and Y . M . Milgrorn, Eur. J . Biochem., 1980, 106, 457. V. W. Armstrong and F. Eckstein, B i o c h m i s t r . ~1979, , 18, 5117. Y-H. H . Wong, F. B. Winer, and P. A . Frey, Biochemistry, 1979, 18. 5332. Y-H. H. Wong and P. A. Frey, Biochemistry, 1979, 18, 5337. M. Ikehara, E. Ohtsuka, and A . F. Markham, Arb. Carbohydr. Chem. Biochrm., 1979, 36, 135.

Nuckotides and Nuclcic Acids

191

The 'phosphotriester' method is presently the method of choice in oligonucleotide synthesis. The basic building block for this method is a nucleoside 3'phosphotriester in which the 5'- (and, if present, 2'-)hydroxy-groups are blocked by acid- or base-labile protecting groups, the amino-groups (if any) on the heterocycle are blocked by base-labile protecting groups, and the non-nucleosidic functions that are attached to phosphate may be removed with high specificity. Much effort has been directed towards the efficient synthesis of such intermediates. I f N '-isobutyryl-5'-O-dimethoxytrityl-2'-deoxyguanosine is treated with excess 4-chlorophenyl phosphorodichloridite (in THF, at - 78 "C, and in the presence of 2,6-lutidine) and subsequently with 2-cyanoethanol (at - 78 "C), and the resulting phosphite triester is oxidized with iodine in aqueous T H F at -20 "C, the product (90) is formed in good yield, and similarly good results are obtained for the other common deoxynuc1eosides.l3* When 5'-monomethoxytrityL2'-deoxythyrnidine is treated with the appropriate alkyl aryl phosphorobromidate in pyridine solution at - 20 "C, products of type (91) are obtained.139 The alkyl group [nay be removed from (91) quantitatively, using thiophenol in acetonitrile; t-butylamine at reflux temperature is reported to be equally effective.'-'* The alkyl aryl phosphorobromidates, prepared by oxidation of the corresponding alkyl aryl phosphite with bromine, are preferred to the alkyl aryl phosphorochloridates because the latter react more slowly and afford more side-products. If 2-chloro-4-t-butylphenol is treated firstly with phosphoryl chloride and then with 2,2,2-tribromoethanoI, 2,2,2-tribromoethyl 2-chloro-4-tbutylphenyl phosphorochloridate (92) is formed, and if base-protected 5'-0(4-chlorophenoxy)acetyl-2'-deoxynucleosidesare treated with this reagent they afford the corresponding 3'-phosphotriesters (93) i n good yields.l4' The tribromoethyl group is readily removed, using zinc and 2,4,6-tri-isopropylbenzenesulphonic acid, and the t-butyl group confers useful lipophilicity on intermediates in the phosphotriester synthesis. If 2-chlorophenyl phosphorodichloridate is treated with 1 H-l,2,4-triazole in acetonitrile, 2-chlorophenyl phosphoro[bis( 1,2,4,-triazolidate)] is formed. When a suitably 5'-protected 2'-deoxyribonucleoside is treated with an excess of this reagent, and the products are hydrolysed, the corresponding 3'-(2-chlorophenyl) phosphate (94) is formed directly in very high yield, thus obviating the necessity of selectively deblocking intermediates of type (90)-(93) prior to the next (condensation) step in phosphotriester synthesis.132 It is noteworthy that phosphodiesters of type (94) are also formed in high yields, in one step, if alkyl aryl phosphorobromidates are treated with pyridine at - 20 "C for 30 min before being used to phosphorylate 5'-blocked 2'-deoxyribonucleosides in pyridine at ambient temperatures. 13H 1-Mesitylenesulphonyl-3-n~tro-l,2,4-triazole (MSNT) is a most effective reagent for condensing phosphodiesters such as (94) with the 5'-hydroxy-group of another deoxynucleoside or deoxynucleotide, and it is not necessary to protect D. Molko, R . B. Derbyshire, A. Guy, A . Rogct, and R. Teoule, Tetrahedron Lett., 1980,

21, 2159. 1.41

N . T. Thuong and M.Chassignol, Tctraheclron Lctt., 1980, 21, 2063. D. J . H . Smith, K . K . Ogilvie, and M . F. Gillen, Terraliedron Lrtt., 1980, 21, 861. R . Arentzen, C . A. A. Van Boeckel, G . Van Der Marel, and J. H . van Boom, Synrlwsis, 197Y.

1'82

J . B . Chattopadhyaya and C. B. Reese, Tetralietlron Lptt., 1979, 5059.

139

137.

192


0

I I OR2

0-P-OR'

(90) R' = CH2CH,CN; R'= 4-C1C,H4; R' = (4-MeOC6H4),(Ph)C;B = N -ibuGua-9 (91) R'= Me or Et; R'= 2- or 4-C1C6H4;K3= (4-MeOC6H4)(Ph),C; B = Thy-1 (93) R' = CBr,CH,; R2= 2-Cl-4-ButC6H3;R3 = 4-ClC6H40CH2CO;B = Thy-1, N "-bzAde-9, N '-anCy t-1 ,or N ,-bzGua-9 (97) R' = %Ba2+;R 2 = 4-C1C6H4;R 3 = (4-MeOC6H4),(Ph)C;B = Thy-I, N6-bzAde-9, N4-bzCyt-l, or N 2-ibuCua-9

0

an = anisoyl bz = benzoyl ibu = isobutyryl

0

I 0-P-R' I OR

OR4

(95) R ' = OH, R 2 = 5-chloro-8quinolyl; R3= (4-MeOC,H4),(Ph)C; R4 = tetrahydropyranyl; B = Ura-1 (96) R' = OCH2CH2CN;R2,R3,R4, and B as in ( 9 5 ) (99) R' = NHPh; R' = 4-C1C,H4; R3= (4-MeOC,H4)(Ph),C; R4 = 2-N02C,H4CH,; B = Ura-1, N6-bzAde-9,N'-bzCyt-l, or N l-ibuGua-9

the 3'-hydroxy-group of the sugar in the first case, the quantity of 3'-3'-linked product obtained being less than 2 % . l a 2Phosphotriester formation using arenesulphonyl triazolides a n d phosphorylation a t 3'-hydroxy-groups with chlorophenylphosphoro( bis-triazolidates) are both strongly catalysed by tertiary bases, a n d particularly by 4-(dimethy1amino)pyridine. 143 The use of phosphoro143

V. N. Dobrynin, N. S. Bystrov, B. K. Chernov, I. V. Severtsova, and M. N . Kolosov, Bioorg. Khitn., 1979, 5 , 1254 (Chem. Abstr., 1980, 92, 164 212).

Nuclcotidcs arid Nuclcic Acids

193

triazolidates and arenesulphonyl triazolides in phosphotriester syntheses of oligonucleotides is nicely exemplified in the preparation of a tridecanucleoside dodecaphosphate sequence of SV 40 DNA.14‘ However, the use of MSNT in coupling reactions is not without snags. When N 2-benzoyl-2’,3’,5’-tri-0-acetylguanosine and 2‘,3’,5’-tri-O-acetyluridineare treated with MSNT in pyridine, the 6-oxygen function of guanine and the 4-oxygen function of uracil are replaced by 3-nitro-1,2,4-triazole, presumably uiu attack of this base on the 6- and 4-0arylsulphonates that are formed as intermediates.145Moreover, this side-reaction is catalysed by phosphodiesters, and care must therefore be taken that in condensation reactions neither MSNT nor phosphodiester is present in excess, and that the reaction time is kept as short as possible. When TPS-tetrazole or benzenesulphonyltriazole have been used to effect condensation reactions, sulphonation of the component that bears the 5’-hydroxy-group has been but this is minimized if the other component of the reaction is a 3’-0-(4-~hlorophenyl) phosphate. Here the relative rates of condensation and sulphonation are critical, and condensation proceeds fastest when an aryl phosphodiester is employed. When reagents such as (92) are used to phosphorylate, at the 3’-hydroxy-group, those nucleosides that bear acid-sensitive groups at the 5’-position, the addition of powdered molecular sieves to the reaction mixture (to scavenge for HCI that is formed) has been found to be benefi~ial.’~’ In a critical comparison of the utility of different condensing agents in coupling silylated ribonucleosides and ribonucleotides,148 the t-butyldimethylsilyl (TBDMS) protecting group remained stable throughout coupling procedures employing arene nitroimidazoles, triazoles, tetrazoles, and TPS-CI.14gHowever, the particular proponent of the use of silyl groups as protecting groups favours the use of trichloroethyl phosphorodichloridite to introduce the inter-nucleotidic link,lgBand has demonstrated its efficacy in the synthesis of the 3’-terminal heptanucleotide sequence of tRNAfMetfrom E. coli. 150 The 5-chloro-8-quinolyl group has been used as an efficient phosphateprotecting group in oligoribonucleotide synthesis. Treatment of 5’-O-dimethoxytrityl-2’-0-tetrahydropyranyluridinewith one equivalent of 5-chloro-8-quinolyl phosphate and two equivalents of quinoline-8-sulphonyl chloride (a novel coupling reagent)161 affords (95) in quantitative yield.152Compound (95) may be coupled with 2-cyanoethanol, using quinoline-8-sulphonyl chloride, to give (96), which is a useful intermediate for the phosphotriester method,153or may be coupled directly to a 2’,3’-di-O-benzoylated nucleoside, using the same condensing agent, to afford a fully protected dinucleoside monophosphate. The 5-chloro144 146 147

14% 149

150 151 152

153

J . B. Chattopadhyaya and C. B. Reese, Nuelc~icAcids Res., 1980, 8, 2039. C. B. Reese and A . Ubasawa, Tetrahedron Lett., 1980, 21, 2265. A. Kraszewski. J . Stawinski, and M . Wiewiorowski, Nuclcic Acids Res., 1980, 8, 2301. V. Kohli, H . Blocker, and H. Koster, Tetrahedron Lett., 1980, 21, 501. K. K . Ogilvie, A. L. Schifman, and C. L. Penney, Con. J . Chem., 1979, 57, 2230. K . K . Ogilvie and R. T. Pon, Nucleic Acids Re.s., 1980, 8 , 2105. K . K. Ogilvie and N . Y . Theriault, Can. J . Cheni., 1979, 57, 3140. H . Takaku, M . Yoshida, M. Kato, and T . Hata, C h c t ~Lett., ~. 1978, 81 1 (Chetit. Ahstr.,

1979,91, I75 654). H . Takaku, R. Yamaguchi, T. Nomoto, and T. Hata, Tetrahedron L e f t., 1979, 3857. H . Takaku, T. Nomoto, Y . Sakamoto, and T. Hata, CIiem. Lett., 1979, 1225 (Chem. Ahstr.. 1980, 92, 4 2 3 16).

194

Organophosphoriis Chemistrj,

8-quinolyl group is removed by using zinc chloride in aqueous pyridine at room temperature. The 2-(4-nitrophenyl)ethyl group has also been commended as a phosphate-blocking group for use in oligonucleotide synthesis. 154 It is readily removed by 1,5-diazabicyclo[5.4. OIundec-5-ene or by 1,5-diazabicyclo[4.3 .O]non-5-ene. A study of fluoride-ion-promoted deprotection and transesterification in phosphate (and particularly nucleotide) triesters has confirmed the dangers inherent in using this reagent to remove phosphate-protecting groups.’jS Initial formation of phosphorofluoridate may be followed by hydrolysis to a phosphodiester, or transesterification, or cleavage of inter-nucleotide bonds. Certain phosphate-protecting groups, such as the 4-N-benzylaminophenyl group, are amenable to selective removal by anodic ~ x i d a t i o n , ’but ~ ~ scope for the use of this technique seems rather limited. Following the removal of the phosphateblocking 2,2,2-trichloroethyl groups from a fully protected heptanucleotide, using zinc and acetylacetone, purification of the product by chromatography o n Sephadex LH 20 reportedly results in a spectacular increase in ~ie1ds.l~’ Barium salts of protected deoxyribonucleoside 3’-(4-chlorophenyl) phosphates may conveniently be used for the high-yield synthesis of dinucleotide blocks for the triester ~ y n t h e s i s . ’Thus, ~ ~ (97) may be treated with 2-cyanoethanol and TPS-4-nitroimidazole to give an intermediate of type (90),which is then treated with benzenesulphonic acid to remove the dimethoxytrityl group and coupled with another molecule of type (97) to afford the fully protected dinucleoside diphosphate. All sixteen dinucleotide blocks have been prepared, in high yield, in this way. Treatment of 4-chlorophenyl phosphorodichloridate with aniline affords 4chlorophenyl N-phenylchlorophosphoramidate (98), which is a new phosphorylating reagent. 159 When 5’-0-monomethoxytrityl-2’-0-(2-nitrobenzyl)-ribonucleosides are treated with (98), triesters (99) are formed, which are convenient for oligoribonucleotide synthesis, the anilido-group being removed by isoamyl 160

While dianilidophosphoryl chloride is a convenient reagent for introducing a phosphate group at the 5’-terminus of shorter fully-protected oligonucleotides,lG0 it fails to phosphorylate the fi’-hydroxy-group on otherwise fully protected decathymidylate.161 This difficulty may be circumvented by joining appropriately phosphorylated shorter blocks. Functionalized DNA fragments that bear a primary amino-group attached to the 5’-terminus have been prepared and coupled to cellulose that was activated with 2,4,6-trichloro-s-triazineor 2-amin0-4,6-dichloro-s-triazine.~~~ While the synthesis of the fragments (mostly E. Uhlmann and W. Pfleiderer, Tetrahedron Lett., 1980, 21, 1181. K . K . Ogilvie and S. L. Beaucage, Nuelpic Acids Res., 1979, 7, 805. 1 5 6 E. Ohtsuka, T. Miyake. M . Ikehara, A . Matsumoto, and H . Ohmori, Chrtn. Phnrm. Bull.. 1979, 27, 2242. 1 5 7 K . Grzeskowiak. R . W. Adamiak, and M . Wiewiorowski, NucIeic Acids Rcs., 1980, 8, 1097. 1 5 8 G . R . Gough, K . J . Collier. H . L . Weith, and P. T . Gilham. Nucl(4c A c i h RCJS., 1979, 7 . 1955. 159 E. Ohtsuka, T. Tanaka, and M. Ikehara, J . Am. Clwm. Sor., 1979, 101, 6409. lgnE. Ohtsuka. T. Tanaka, and M. Ikehara, Cham. Phartn. Bull.. 1980, 28, 120. J . F. M. de Rooij, G . Wille-Hazeleger. A . B . J . Vink. and J . H . van Boom, Tctruhw‘roti, 1979, 35, 29 13.

154

155

Nuclmtides arid Nucleic acid^

195

oligothymidylate) follows regular phosphotriester methods,162the 5’-terminus is chosen so as to allow subsequent removal from the cellulose by base (5’-0glycylthymidine as the 5‘-terminus), by acid 1 thymidine 5-[N-(4-aminobenzyl)]phosphoramidate as the 5’-terminusl, or by enzymic cleavage (5’-amino-5’deoxythymidine at the 5’-terminus of an oligothymidylate chain that contains a single uridylate residue).161Following cleavage from the cellulose, linkage could be shown to have taken place exclusively riu the functionalized 5’-terminus. Other notable examples of the phosphotriester method include the synthesis of seventeen deoxyribo-oligonucleotide fragments of the insulin gene l g 3 and of ribo-oligonucleotide fragments corresponding to an inter-cistronic regional sequence of mRNA from E. coli.“jJThe phosphodiester method has been used to assemble a deoxyribohexanucleotide corresponding to the recognition sequence of the restriction endonuclease Eco R1,165and, in another tour de force from Khorana’s laboratory, the DNA of a tyrosine suppressor tRNA gene,166which is 207 base-pairs long. Several promising attempts to perform phosphotriester syntheses on polymer supports have been detailed. Three of these involve the initial attachment of the 3’-hydroxy-group of 5’-0-dimethoxytrityl-2’-deoxythymidine ciu a carboxylate ester link to a functionalized polymer which may be aminopropylsilylated silica gel,16i a polyamide gel, 168 o r partially hydrolysed cross-linked polyacrylmorpholide. 1 6 @ 0

AcO

b I

O=P--OC,,H4C14

I

0

I

MeO-P-CI

I

?

. F. M . de Kooij, G . Wille-Hazeleger, P. H . van Deursen. J . Serdijn, and J . H . van Boom, Kocl. Trtir. Cliiiti. Pri~*.~-Bos. 1979. 98, 537. W . L. Sung, H . M . Hsiung, R . Brousseau, J . Michniewicz, R . Wu, and S. A . Narany, Nirclvic Acitls R P S . , 1979, 7 , 1199. T. Neilson. K.J . GreEoire. A . R . Fraser, E. C. Kofold, and M . C . Ganoza. Eur. J . Bioc~liciri.. 1979. 99, 419. ti. Ohtsuka. R . Fukumoto. and M . Ikehara. Chcrii. PIiwiu. Bull, 1980, 28, 80. R . Belagaje, E. L. Brown, M. J . Gait, H . C i . Khorana, and K . E. Norris, J . B i d . Ciiciv., 1979. 254, 5754. and following papers. M . D. Matteucci and M . H . Caruthers, Tc~tr~ihrrlroti Lcjlr.. 1980, 21, 719.

Iti2J

I li5 I lili 11;;

I iin 169

M . J . Gait, M. Singh. R . C. Sheppard, M . D. Edge, A . K.Greene, G . R . Heathcliffe. T. C. Atkinson, C. R . Newton. and A . F. Markham, Nuc,lcic. Acids Res., 1980. 8. 1081. K-i. Miyoshi and K . Itakura, Tcrrahrtlroti Lcrt., 1979, 3635.

196

0rganop hosphorus Chemistry

In the fourth the same terminus is attached to cellulose riu a uridylate residue, by first synthesizing ( 100) by standard methods and coupling the phosphodiester to the polymer with TPS-tetrazole. The dimethoxytrityl group is then removed by washing with an arenesulphonic acid, in each case. In one procedure,1s7the inter-nucleotidic link is formed by the reaction of the 5’-hydroxy-group of the immobilized thymidine with (101) and subsequent oxidation with iodine in aqueous T H F to form the methyl-protected phosphotriester. In others,1ss*170 a building block of type (97) (but with a different cation in place of barium) is coupled t o the thymidine residue, using TPStetrazole. Alternatively, the same condensing agent is used for the stepwise addition of protected trimer blocks, the underlying idea being that, during the final product separation, oligonucleotides that differ in length by three residues are more readily separated chromatographically than those differing by only one On completion of the elongation cycles, the methyl groups are removed from the phosphotriesters with thiophenol and the oligomer is removed from the support with concentrated ammonia in the first procedure1s7 (which reported high yields) or with 4-nitrobenzaldoximate 168 or concentrated a m n i ~ n i a , 1’7~0 which ~~ were used for simultaneous deblocking of the phosphotriesters and cleavage from the polymer in the other methods. However, there may be some risk of chain cleavage or of isomerization at the inter-nucleotidic link if both of these reactions are performed concurrently, with a single reagent. N o less than six new methods for the synthesis of the protein-synthesis inhibitor pppA2’p5’A2’p5’A 1 7 1 - 1 7 3 or its ‘core’ t rinucleoside di phosphate, A2’~5’A2’p5’A,”~have been published. Four of these 1711 174 employ stepwise phosphotriester methods similar to those described above. In another procedure,I7? Ns-benzoyl-3’-O-(2-nitro)benzyladenylic acid is first synthesized, and then oligomerized with DCC. Following debenzoylation, the protected trimer, formed in 6 % yield, is irradiated to remove the nitrobenzyl groups and converted into the required 5’4riphosphate with carbonyldi-imidazole and pyrophosphate. The last method 173 takes the prize for simplicity and directness. Adenosine 5’-phosphorimidazolidate is stirred with lead nitrate in imidazole buffer, at pH 6.5, for 5 days. Under these conditions, the 2‘-5‘ link is formed preferentially. Removal of the lead by chelation and separation of the products on QAE-Sephadex affords pA2’p5’A2’p5’A in 9 % yield. Conversion into the triphosphate is performed as described above. Oligonucleotide analogues containing inter-nucleoside phosphite links have been described.175Treatment of 5’-O-phenoxyacetylthynidinefirstly with 2,2,2trichloroethyl phosphorodichloridite in T H F at - 78 “C, and then with 3 ’ 4 monomethoxytritylthymidine, affords (102) in good yield. Removal of the phenoxyacetyl group with ammonia and repeated coupling as above yields the lio

li3 174

R . Crea and T. Horn, Niccli~icAcids Rcs., 1980, 8, 2331. S. S. Jones and C . B. Reese, J . Am. C/ic,t?i.Soc., 1979, 101, 7399; J . A. J . den Hartog. J . Doornbos, R. Crea, and J . H . van Boom, R i d . Truv. Chim. Pays-Bus, 1979,98. 469. M . Ikehara, K . Oshie, and E. Ohtsuka, Ti,truhetlron Lett., 1979, 3677. H . Sawai. T. Shibata. and M . Ohno, T c t r u h d - o n Lrtt., 1979, 4573. J . Engels and U . Krahnier, Angrw. Chrm., Int. €d. Engl., 1979, 18, 942; R . Charubala and W . Ptleiderer, Tctrulicdron Lett., 1980, 21, 1933. R . P. Melnick, J . L. Finnan, and R . L . Letsinger, J . O r g . Chem., 1980, 45, 2715.

Nucleoticks and Nucleic AciL1.Y

I97

I

R

(102)

(103)

Cl ,CCH 2O MMTr = (4-MeOC,H4)(Ph),C DMTr = (4-MeOC,H4),(Ph)C

R = Me or Ph B

=

Thy-1, N ,-bzAde-9, N 4-anCyt- 1 ,or N 2-ibuGua-9

corresponding protected trinucleoside diphosphite. Oxidation of (102) with iodine in aqueous TH F affords the corresponding phosphotriester quantitatively. Oligodeoxyribonucleotidescontaining methyl- and phenyl-phosphonate 177 Treatment of 5’-O-dimethoxytrityl-2’linkages have also been prepared. deoxy-nucleosides with methyl- or phenyl phosphonobis(triazo1idate) affords the corresponding 5’-O-dimethoxytritylnucleoside-3’-O-methylor -phenyl-phosphonotriazolidate; on consecutive treatment with benzenesulphonyltetrazole and another 2’-deoxynucleoside, this gives ( 103) in good ~ i e 1 d . lThe ~ ~ methylphosphonates (103)are unstable in alkali at room temperature, but the phenylphosphonates are relatively stable. Both types may be deblocked, using concentrated ammonia followed by benzenesulphonic acid, to yield the dinucleoside alkylphosphonates. The diastereoisomers of d(Tp(Me)T} and d{Tp(Ph)T} are separable by t.1.c. Both diastereoisomers of each compound are completely resistant to spleen phosphodiesterase, but can be phosphorylated using [p3*P]ATPand polynucleotide kinase. One diastereoisomer of each compound is hydrolysed slowly by snake venom phosphodiesterase. Similar results have been reported for the separated diastereoisomers of d{Ap(Me)A}, which is prepared by pseudo-phosphotriester Interestingly, these oligonucleotide analogues are.taken up by cells in culture. Dicytidylyl(3’49-1,2-di(adenosin-N6-yl)-ethane and -butane have been described.”* These molecules, effectively two CpA units with the adenine rings joined through N-6 by dimethylene and tetramethylene bridges respectively, show different susceptibilities to snake venom phosphodiesterase, with only the latter species undergoing partial degradation. Differential stacking and rotamer populations are thought to account for the difference. The octanucleotide d(T-G-C-A-C-A-T-G) possesses two ‘sticky ends’ and self-associates in solution, forming double-helical concatemers similar to type B helices of DNA.17Q Phosphorylation of the octamer, using [ Y - ~ ~ P I Aand T P T4 polynucleotide kinase, followed by polymerization, using a water-soluble carbodi-imide, under conditions of concatemer stability, afforded 13 ”/, yield of the octanucleotide dimer. 1767

178

l77 lis

179

K. L. Agarwal a n d F. Riftina, N d c i c Acids RPS., 1979, 6, 3009. P. S. Miller, J . Yano, E. Yano, C. Carroll, K. Jayaraman, a n d P.O.P. T’so, Biocherni.stry, 1979, 18. 5134. J. kemlitka. Biochi~mistry, 1980, 19, 163. Z. A. Shabarova, N. G . Dolinnaya, S. I. Turkin, a n d E. S. G r o m o v a , Nuclcic Acids R e s . , 1980, 8, 2413.

198

Orguriophosphorus Chcmistr,.

Enzymatic Synthesis.-Poly(5-ethynyluridylic acid) has been prepared. The nucleoside, which is readily hydrated in mildly acidic conditions, is phosphorylated with 2,2,2-trichloroethyl phosphoromorpholinochloridate (a reagent that is specific for the 5'-position), the trichloroethyl group is removed with zinc and acetylacetone, and the resulting 5'-phosphoromorpholidate is treated with phosphate, affording 5-ethynyluridine 5'-diphosphate, which is a substrate for polynucleotide phosphorylase from Micrococcits Iirrrus.l M 0Poly(5-ethynyluridylic acid) possesses an ordered structure in solution, even at low ionic strength, and forms only a rather stable 1 : 1 complex with poly(A), in marked contrast to poly( U). While 8-azido-ADP and 8-azido-I DP fail to form homopolynucleotides on incubation with polynucleotide phosphorylase from Escherichiu coli, they can be copolymerized with ADP and IDP, respectively, using this enzyme i n the presence of Mn'. ions, yielding poly(A,zXA)that contains up to 26'::) of S-azidoadenylic acid and poly(I,zsI) that contains up to 3 % of 8-azidoinosinic acid.IX* If the azidonucleotide content of the copolymers is kept low, poly(A,z8A) forms a triplex with two poly(U) strands, and poly(I,zsI) a duplex with poly(C). Poly(A,zsA) can act as a template, directing the synthesis of poly(U) by RNA polymerase, but the enzymic activity is lost on irradiation, with the /L, /i'-, and +subunits becoming attached to the polynucleotide, suggesting that these copolymers show promise as photoaffinity reagents. The fluorescent analogue 1 ,Ns-etheno-2-aza-adenosine may be incorporated into poly(A), poly( U), or poly(1) by copolymerization of its 5'-diphosphate with ADP, UDP, and IDP, respectively, using polynucleotide phosphorylase.lM2The physicochemical properties of the copolymers containing less than 10% of the fluorescent base are similar to those of poly(A), poly(U), and poly(l), respectively, and the analogue residues may thus be used as fluorescent structure probes in processes involving these polynucleotides. Treatment of poly(cytidy1ic acid) with methyl hypobromite in dry methanol, followed by sodium hydrosulphide, results in the conversion The thiolation, of some of the cytidine residues into 5-mer~aptocytidine.~"'j which appears (from enzymic digestion studies) to take place at random, disrupts the normal poly(C) structure, and results in the formation of inter- and intramolecular disulphide links. Deoxynucleotide copolymers containing O"-methyldeoxyguanylic acid have been prepared with a view to studying the stability and repair of DNA that contains this 'promutagenic' lesion. lW4 06-Methyldeoxyguanosine, another acid-labile nucleoside, is converted into its 5'-monophosphate (using carrot phosphotransferase) and thence, with carbonyldi-imidazole and pyrophosphate, into the 5'-triphosphate, which is copolymerized with dCTP or dTTP by terminal deoxynucleotidyf transferase. The stability of O"-methyldeoxyguanosine in poly(dT, m6dG)decreased markedly with pH below neutrality. Polynucleotide analogues continue to provoke interest in the fashionable area of interferon research. Analogues of poly( 1). poly(C) that contain 2'-fluoro2'-deoxyinosinic acid or 2'-chloro-2'-deoxyinosinic acid in place of inosinic E. Biala, A . S. Jones. and R . T. Walker, Tcrralic~lroii,1980, 36, 155. I . L. Cartwright and D. W. Hutchinson. Nuc/oic Acids Rcs., 1980. 8, 1675. K . F. Y i p and K . C. Tsou. Biopolj~nirrs, 1979, 18, 1389. lH:l Y . - K . H o , R . J . Fiel, J . Aradi, and T . .I.Bardos. Biochrmisrr,., 1979. 18, 5630 IHJ P. J . Abbott, J . R . Mehta, and D. B. Ludlum. Bioch>misrr,,, 1980. 19, 643. IH1


199

acid,IH5or in which up to lo:< of the inosinic acid residues are replaced by uridylic acid [resulting in mismatched pairs in the poly(I ) poly(C) duplex], ln6 are effective inducers of interferon, strengthening the idea that the overall conformation of the duplex, rather than a specific functional group (such as 2’-hydroxy) requires to be recognized, and that an intact double-helical segment that is about 10 base-pairs long is necessary to elicit the interferon response. As the name suggests, T4 RNA ligase normally joins the 3’-hydroxy terminus of an acceptor oligoribonucleotide to the 5’-phosphorylated terminus of a donor oligoribonucleotide in the presence of ATP. I n the presence of Mn’. and low concentrations of ATP plus an ATP-regenerating system (e.g. phosphocreatinecreatine kinase-myokinase), the same reaction can be effected with oligodeoxyribonucleotides.1M7Thus dA(pdA), is coupled with [5’-‘32P](pdT),pdCpto afford dA(pdA),[3’-5’-“2P]pdT(pdT),pdCp in yields up to 60 yi, which may be increased if excess acceptor is used. Indeed, pdAp, pdCp, pdGp, pdTp, and pdUp can be ligated to dA(pdA), in high yields.InHI t is required that the 3’-terminus of the donor should bear a phosphate or other blocking group, since otherwise oligomerization may occur. This procedure appears to obviate the need to synthesize complementary sequences in order to join stretches of DNA, as required by DNA ligase. T4 RNA ligase has been used to link a chemically synthesized tetraribonucleotide, a hexaribonucleotide, and a decaribonucleotide to form the eicosanucleotide which corresponds to the base sequence 1-20 of tRNAf3“’t from E. coli.’H9Oligonucleotide chains are conveniently synthesized, using chemical I y synthesized P ‘-adenosi ne-P 2-( 2’, 3’-O,O-ethoxymet hy1idene)nucleosidepyrophosphates as single-addition substrates for T4 RNA ligase and an acceptor chain that is three or more residues long.*9oA wide range of adenylate analogues may also be ligated to the 3’-terminus of ApCpC, by initial chemical adenylation to form the unsymmetrical 5’,5’-pyrophosphates followed by treatment with T4 RNA ligase and the acceptor. The symmetrical pyrophosphates of the adenylate analogues were not donor substrates, emphasizing a strict requirement for adenylate as cofactor.l g o Several polynucleotide block polymers that consist of a D N A - R N A hybrid joined to a DNA.DNA duplex of the type (dG)i-(rC)k(dC),( k = 10-48, i= 10-60) have been prepared and c h a r a ~ t e r i z e dIn . ~the ~ ~ key step, (rC)iand (dC)k,the latter acetylated at the 3’-terminus, were annealed to (dI), and joined, using T4 DNA ligase, since T4 RNA ligase was found to be unsatisfactory. After thermal dissociation, (dl), was replaced by (dG),. Oligoribonucleotides may also be synthesized by utilizing 2’-0-(2-nitrobenzy1)nucleoside 5‘-diphosphates as single-addition substrates for polynucleo*

1:. de Clercq, B. D. Stollar, J . Hobbs, T . Fukui. N . Kakiuchi, and M . Ikehara, Eur. J . Bioclicni., 1980, 107, 279. IHfi E. de Clercq. G.-F. Huang, B. Bhooshan, G . Ledley. and P. F. Torrence. Nuclcic A(,id.s R c s . , 1979, 7 , 2003. I H 7 M . I . M . McCoy and R. I . Gumport, B i o ~ h ~ r i i i s t r1980, y, 19, 635. I B R D. M. Hinton and R. I . Gurnport, N u d k Acids Rcs., 1979, 7 , 453. l R D E. Ohtsuka, S. Nishikawa. R. Fukurnoto, H. Uernura, T. Tanaka, E. Nakagawa, T. Miyake, and M . Ikehara, Etir. J . Biochein., 1980, 105. 481. l v o E. Ohtsuka, T . Miyake, K. Nagao. H . Uernura, S. Nishikawa, M . Sugiura, and M . Ikehara, Niicli>icAcids Rc,.s., 1980, 8, 601. E. Selsing and R . D. Wells. J . B i d . Chrm., 1979, 254. 5410.

200


tide phosphorylase from E. coli or M . luteus, adding residues one at a time to the 3’-terminus of a short oligoribonucleotide template.lQ2Following each addition, the product is irradiated to remove the 2-nitrobemzyl group, prior to adding the next residue. Polynucleotide phosphorylase from Thermrts thermophilus has been used to add short guanylyl blocks, either one or two residues long, to the 3’-termini of (Ap),A and (Up),U primers.19” I f a DNA fragment that bears a 3’-hydroxy-group is incubated with 4-thiouridine 5’-triphosphate and terminal deoxynucleotidyl transferase, and the product is incubated with pancreatic ribonuclease, a single 4-thiouridine residue is left at the 3’-terminus of the DNA. This terminal residue may be specifically alkylated with iodoacetamide or with fluorescent labels that contain a-halogenoacetamide groups, thus providing a method for the specific chemical labelling of DNA.194 Sequencing.-Modern methods of DNA sequencing have been reviewed. l H 5 Double-stranded DNA, labelled with 32Pat a single 5/-terminus, may conveniently be sequenced by an adaptation of the Maat-Smith and Sanger-Coulson techniques reported If DNA is treated with formaldehyde in the presence of primary amines, adenine units are lost from the chain. Hence, if end-labelled single-stranded DNA is incubated with a concentration of formaldehyde and ethanol that is sufficient to provide one statistical ‘hit’ per chain, and then treated with piperidine to cleave the chain at depurinated positions, separation on a polyacrylamide gel generates a ladder of chain lengths corresponding to adenine One major problem in RNA sequencing is that no enzymes are known which cleave RNA chains at specific sequences in the way that restriction endonucleases cleave DNA sequences. However, ribonuclease H specifically cleaves RNA DNA hybrids. Hence, hybridization of an oligodeoxyribonucleotide (tetramer or longer) to the RNA chain and treatment with RNase H effects addressed fragmentation of the RNA molecule at any sequence that is complementary to the added DNA oligomer, and the RNA fragments may be end-labelled and sequenced by standard methods. l Q 8 A novel direct-readout RNA-sequencing technique has been described, 9 9 * 2oo An RNA molecule is subjected to brief hydrolysis in hot waterlg9 or DMF200 to produce roughly one hydrolytic break per chain. The 5’-hydroxy-groups thus generated are phosphorylated with [y-32P]ATPand polynucleotide kinase and then separated on a polyacrylamide gel, giving a ladder of all chain lengths. The gel bands are transferred by blotting on to a P E I - c e l l u l ~ s eor ~ ~DEAE~ E. Ohtsuka, S. Tanaka, M . Hayashi, and M. Ikehara, Biochim. Biophys. Acrci, 1979, 565, 192. l g 3 Y. Kikuchi, K. Hirai, and K . Sakaguchi, J . Biochem. (Tokyo), 1979, 86, 1427. l e 4 H. Eshaghpour, D. Soll, and D. M. Crothers. Nucleic Acids Res., 1979, 7, 1485. lg5 S. M . Weissman, Anal. Biochem., 1979, 98. 243. l g 6 1. Seif, G . Khoury, and R. Dhar, Nucleic Acids Res., 1980, 8, 2225. 197 E. D. Sverdlov, G . S. Monastyrskaya, A . M. Poverenny, Yu.A . Semin, and E. N. Kolomyitseva, FEBS Lert., 1979, 108, 427. l Q B H . Donis-Keller, Nucleic Acids Res., 1979, 7 , 179; 0. B. Stepanova, V. G . Metelev, N . V. Chichkova. V. D. Smirnov, N. P. Radionova. J . G. Atabekov. A. A. Bogdanov, and Z. A . Shabarova, FEBS Lett., 1979, 103, 197. lQ9 R . C. Gupta and K . Randerath, N u c l ~ i cAcids Res., 1979, 6, 3443. Y . Tanaka, T. A . Dyer, and G. G . Brownlee, Nurleic Acids Rm., 1980, 8, 1259.

Nuclrotidrs und Nucleic Aids

20 1

cellulose2oot.1.c. plate and digested it2 situ with ribonuclease T,, releasing the 5’-32P-labelled nucleoside 3’,5’-bisphosphate at the terminus of each RNA fragment. Development of the plate in the second dimension by chrornatography ’O Y or electrophoresis allows the nucleoside 3’,5’-bisphosphates to be identified and the sequence read directly. This technique is particularly convenient for sequencing RNAs that contain modified nucleotides. I f RNA is treated with niethoxyamine and bisulphite, the cytidine residues are converted into N4-methoxy-5,6-dihydrocyt idine 6-sulphonate, G-C: pairs in any double-stranded regions are disrupted, and the secondary structure unfolds. Since the regions of RNA that are involved in secondary structure are only poorly hydrolysed by RNase compared with single-stranded regions, pretreatment with methoxyamine and bisulphite gives a more uniform set of fragments after partial hydrolysis with RNase.201Moreover, after complete modification of cytidine residues with this reagent, the specificity of RNase A is restricted to chain cleavage on the 3‘-side of uridine residues, and that of RNase T, to cleavage on the 3’-side of adenosine, guanosine, and uridine residues, permitting the positions of cytidine residues to be established. A ribonuclease which cleaves RNA preferentially on the 3’-side of cytidine residues has been isolated,2o2 and this property is likely to be of value in RNA sequencing.”O” Nucleases of specificity which varies with pH and the metal ion present have been isolated from Stuphylococcus uureus and Neurospora crussa and utilized in RNA sequencing. 205 If RNA is digested with nuclease S, (which digests single-stranded regions) and then subjected to two-dimensional gel electrophoresis in which the first dimension is run in non-denaturing conditions and the second dimension in denaturing conditions, the regions of RNA which were involved in secondary structure in the native molecule which persisted in the first dimension are separated to give pairs or families of fragments in the second dimension. These fragments are isolated, sequenced, and matched against the known sequence of the RNA molecule to determine interacting regions in the original m 0 1 e c u l e . ~ ~ ~ A variation of the old copy-synthesis technique has been used to determine sequences adjacent to the poly(A) tail of mRNA molecules. Synthetic oligodeoxyribonucleotide primers of general sequence d[(pT),NpN’] (where N is rlot thymidine) are incubated with the mRNA molecule, reverse transcriptase, and a mixture of 2’-deoxynucleoside 5’4riphosphates containing a single 2’,3’dideoxynucleoside 5’-triphosphate as chain terminator. Only when N and N’ complement the sequence adjacent to the poly(A) tail of the mRNA are unique fragments obtained in the dideoxy sequencing reaction, and the sequence of the newly synthesized material, and hence (by complementarity) that of the mRNA, is thus identified.’06 ?O1

202 203

m5 “06

A . M. Mazo, T. D. Mashkova, T. A . Avdonina. N . S. Arnbartsumyan, and L. L . Kisselev, Nuclcic Aciils Res., 1979, 7.2469. C . C . Levy and T. P. Karpetsky, J . B i d . Chrm., 1980, 255, 2153. M. S. Boguski, P. A. Hieter, and C. C. Levy, J . Biof. Chem., 1980. 255, 2160. G . Krupp and H . J . Gross, Nucleic Acids Rrs., 1979, 6,3481. A , Ross and R. Brirnacom be, Nature (London),1979. 281, 27 1 . N . L. Sasavage, M. Smith, S. Gillam, C. Astell, J . H. Nilson, and F. Rottman, Biochrmistr,v, IY80, 19, 1737.

202

Orgariophosphorirs Chcmistrjt

While the widespread application of such a method appears doubtful, fully protected oligodeoxyribonucleotides of up to hexamer length that contain phosphotriester linkages may be sequenced by using the data obtained from positive- and negative-ion 'j'Cf plasma desorption mass spectrometry.'07 Other Studies.-Useful reviews on interactions between metal ions and nucleotides .'On and X-ray structural studies o n metal-nucleotide complexes " 0 9 have appeared. The lack of uniformity in the size and direction of chemical shifts in the "P n.m.r. spectra of ADP", AMP2 , and phenyl phosphate dianion on binding Mg' ions has prompted the suggestion that the corresponding shifts observed when Mg' and Ca" form complexes with ATP are due principally to changes in conformation of the polyphosphate chain rather than to purely electronic effects that occur because the metal ion binds to the phosphooxyanions. 2 1 0 Treatment of poly(adeny1ic acid) with chloroacetaldehyde affords copolymers of adenylate and 1 ,N6-ethenoadenylatein which the proportion of the fluorescent analogue ranges from 9 to nearly The ethenoadenosine residues are distributed non-randomly in the copolymer, suggesting that initial modification alters the local structure in poly(A), facilitating further reaction. Poly(A,tA) appears to have an ordered structure at ambient temperature in aqueous solution. Fluorescent labels may conveniently be introduced into polynucleotides by treatment with sodium bisulphite and I ,3-diaminopropane, whereby cytidine residues are converted into N4-(3-aminopropyl)cytidineresidues, and subsequent treatment with 4-chloro-7-ni trobenzofurazan affords the fluorescent compound ( 104).2'2The degree to which the bisulphite-exchange reaction takes place, and

consequently the amount of fluorescent label which may be introduced, is strongly pH-dependent. The same method has been used to introduce chemically reactive groups into oligodeoxyribonucleotides."'" After the exchange reaction of 2'-deoxycytidine residues with bisulphite and a diaminoalkane, as mentioned above, the free primary amino-group is acylated, using the bromoacetyl ester of "07

208 209 210 "11 912

"13

C . J . McNeal. S. A . Narang, R . D. Macfarlane, H . M. Hsiung, and R . Brousseau. /'roc,. N o t / . A < . ~ i lSt,;. . USA, 1980, 77, 753. M. R . Bruce and Y. H . Mariam, M p t . lotis B i d . S.rst., 1979, 8, 57; H . Sigel. ;bid., p. 125. R . W. Gellert and R . W . Bau, Mpt. Ions Biol. S.~.sr.,1979, 8, 1. F. Ramirez and J . F. Marecek, Biothitn. BiophJ4s.Acra, 1980, 589, 21. A. P. Razzhivin, R. K . Ledneva. G. V. Terganova. Yu. A. Borisov. A . A . Bogdanov, and A . A. Kost, Bioorg. Khini., 1979, 5 , 691 (Chrm. Abstr.. 1979, 91, 51 309). D. E. Draper and L. Gold, Biochrmi.str>~,1980, 19, 1774. M . G. Ivanovskaya, Z. A . Shabarova, and M. A . Prokof'ev, Dokl. Akad. N m k SSSR, 1979. 249, 109 (Chvm. Absrr.. 1980. 92, 129 2 3 2 ) .

Nucleotides and Nrrcleic Acids

203

N-hydroxysuccinimide. A fluorescent label is easily introduced into tRNAPhefrom E. coli by the reaction of the X base (3-[3-amino-3-carboxypropyl]uracil) with

fluorescein isothiocyanate, and shows promise as a sensitive probe of the tertiary structure of tRNAPhc.21L M ~ c hexcitement and speculation in the nucleic acid field has followed the revelation that the self-complementary sequences d(CpGpCpGpCpG) and poly(dG-dC)* poly(dG-dC) assume a left-handed helical arrangement.2 1 5 The basic unit of the helix is a dinucleotide in which the conformations of the guanylic and cytidylic acid residues differ considerably. The cytidylic acid unit has the base in the crrrti conformation, the sugar ring 2‘-ondo, and the guirche-gauche conformation at C(4’)-C( 5’), while the guanylate unit is sjw, 3’-endo, and gauche-trans, respectively. As a result, the deoxyribose phosphate backbone appears as a staggered zig-zag, and the conformation has been christened ‘Z’-DNA. The change from a right-handed to a left-handed helical arrangement in poly(dG-dC) is a saltinduced co-operative conformational change, and it has been suggested that this occurs vici a change in the co-ordination number of the phosphorus atom.216 On adding salt or spermine, the oxygen atoms of phosphate are shielded by the cations and a water molecule is co-ordinated to phosphorus in-line with the 5’-oxygen, producing a trigonal-bipyramidal arrangement. The strain induced upon 0(5’)-C(5’)-C(4’)-0( 1’) is relieved by rotations about the C(4’)-C(5’)and C(I’)-N axes, resulting in the changes observed in the guanylate unit. If this takes place for guanylate in both strands of the helix, the change from righthandedness to left-handedness is accomplished.217 5 Analytical Techniques and Physical Methods The dissociation constants of ATP over a range of temperatures and ionic strengths have been determined, and used to calculate the enthalpies and entropies of dissociation under these The osmotic and activity coefficients of the tetrasodium and tetrapotassium salts of ATP have also been measured.?19 A useful formula that is accurate for predicting the electrophoretic mobilities on neutral paper of nucleotides in the range of molecular weights 200-2000 has been calculated, and may be used to predict whether a given set of nucleotides can be adequately separated at a given pH, and in the initial identification of unknown nucleotides.??O A review on the column chromatography of nucleotides, with particular reference to separation using h.p.l.c., has been published. 2 2 1 Measurement of the 31Pn.m.r. spectrum of tRNAPhe from yeast in the presence and absence of Mg2+and over a range of temperature shows the scattered ”I1 ?15 2’0

“LR

21i#

ml “21

J . A . Plumbridge. H. G . Biumert. M. Ehrenberg, a n d A . Rigler, Niiclcic Acids R r s . , 1980, 8 , 827. D. R. Davies a n d S. Zimmerman, Natiire ( L o n r k ~ n ) ,1980. 283, 1 1 . H . Buck, R c d . Tr ar . Chim. Pa.vs-Bas, 1980, 99, 181. H. Ruck, D . van Aken. J. van Lier, a n d M. Kernper, Rrcl. T r a r . Chim. Pa.t+Bas, 1980, 99, 183. H . C. Malhotra a n d L. K. Sharma, Gazz. Chim. / f a / . . 1979, 109, 113 (Chem. Ahstr., 1979, 91. 158 032). 0. D. Bonner, J . Chcur. ThPrmoJ,w., 1979, 11, 563. S. S. Somrner, Anal. Biorhcm., 1979, 98, 8. K. H. Schram a n d J . A . McCloskey, Chromntogr Sci., 1979, 9, 1149.

2 04


non-helical phosphodiester signals, which are distinct and largely invariant below the thermal melting transition, merging with the main group of signals from helical phosphodiester to give a single signal that corresponds to a random coil conformation above the melting temperature, thus supporting the hypothesis that chemical shifts are sensitive to torsional and bond angles of the phosphate ester group. 2 2 2 Measurements of spin-lattice and spin-spin relaxation times indicate that another transition, at a lower temperature, between two intact tertiary structures also takes places, and the small changes in chemical shifts, with broadening of the signal, that are observed in the scattered peaks in the presence of Mg2+are thought to be due to distortions of bond angles that are associated with this transition. The anisotropies of the 31Pn.m.r. chemical shifts of DNA fibres in the A, B, and C forms, oriented parallel and perpendicular to the magnetic field, indicate that the molecules undergo appreciable rotational motion about the helical axis, and suggest that the orientation of the phosphodiester group, and thus the conformation of the backbone, varies significantly along the molecule. 2 2 3 Conformational fluctuations of DNA 2 2 4 and of polyribonucleotides 225 in solution have been investigated by measurement of spin-relaxation times and other parameters in the 31Pn.m.r. spectra; the results indicate that long-range bending motions and rotational wobbling about P-0 bonds occur, resulting in substantial local fluctuations from the equilibrium geometry in these molecules. The concentration of ATP and other phosphate-containing metabolites may be measured by n.m.r. spectroscopy in tissue preparations such as mouse liver 2 2 6 and even, using a surface-coils technique, in whole animals.227 Moreover, measurement of the signals due to ATP and MgATP allows the concentration of free Mg2+ in intact cells to be calculated, and hence, using equilibrium data for certain enzyme reactions, the kinetically active concentrations of other metabolites, such as ADP, MgADP, and AMP, may be determined. 22H Terbium(ii1) co-ordinates to guanine bases in RNA with much more marked enhancement of its fluorescence than that observed on co-ordination to guanine bases in DNA, On thermal denaturation of DNA, however, the fluorescence enhancement of Tb3+increases more than ten-fold, and the increase in fluorescence enhancement correlates closely with the susceptibility of the DNA to nuclease S, over a range of temperature. 2 2 9 Thus only deoxyguanylate residues in single-stranded regions lead to an increase in fluorescence, and the enhancement may be used to measure the single-stranded content of DNA. The influence of terminal 3’-phosphates and 2’,3’-monophosphates on the conformations of adenylate and cytidylate di- and tri-nucleotides has been 224q

“”2

D. G . Gorenstein and B . A. Luxon, Biochemistry, 1979, 18, 3796. H . Shindo, J . B. Wooten, B. H. Pheiffer, and S . B. Zimmerman, Biochemisrry, 1980, 19,

“ ~ 3

518. 224

“25 “26

?Z7

M. E. Hogan and 0. Jardetzky, Proc. Natl. Acad. Sci. USA, 1979, 76,6341. P. H . Bolton and T . L. James, J . A m . Chenr. Soc., 1980, 102, 25. A. C. McLaughlin, H . Takeda, and B. Chance, Proc. Natl. Acad. Sci. USA, 1979, 76, 5445. J . J . H . Ackerman, T. H . Grove, G . G . Wong, D. G . Gadian, and G . K . Radda, N a t i ~ c

(London), 1980, 283, 167. 229

R. K . Gupta and R. D. Moore, J . Biol. Chem., 1980, 255, 3987. D. P. Ringer, B . A. Howell, and D. E. Kizer, Anal. Biochem., 1980, 103, 337.


205

investigated by studying circular d i ~ h r o i s r nIn . ~ compounds ~~ with the terminal 2’,3’-monophosphate, the unusual puckering conformation of the sugar that is imposed by the cyclic phosphate appears to result in destacking. The X-ray structure of the complex between Staphylococcal nuclease and thymidine 3’,5’bisphosphate, at 1.5 A resolution, has allowed the mechanism of action of this enzyme to be formulated. 23

”31

A . F. Markham, S. Uesugi, E. Ohtsuka, and M. Ikehara, Biochemistry, 1979, 18, 4936. F. A. Cotton, E. E. Hazen, Jr., and M. J. Legg, Proc. Nutl. Acad. Sci. USA, 1979,76,2551.

10

Ylides and Related Compounds ~~~

BY B. J. WALKER

1 Methylenephosphoranes

Preparation and Structure.-The tautomeric equilibrium between phosphine ( I ) and phosphonium ylide (2) forms, and the structure of diethyl(carbomethoxy)methylphosphonate anion, have been investigated, using n.m.r. spectroscopy. A variety of novel ylides have been reported. These include the cyanocarbonylstabilized compound (3) and the tropylium-stabilized ylide (9,obtained from the salt (4) by treatment with water or methanol.4 The ylide (5) does not react with aldehydes or acetic anhydride, although it can be methylated, and its chemical and spectroscopic properties indicate a major contribution from the heptafulvalene structure (5b). R'R'PCH(CO,Me),

__L

H R'R2P=C(C0,Me),

(2)

(1)

P-

1

2 3 -1

Ph,P=-CArC;OCN

(3)

/--.

0. 1. Kolodiazhnyi, Telruhedron Lett., 1980, 21, 2269. T. Bottin-Strazalko, J. Corset, F. Frornent, M . J. Pouet. J. Seyden-Penne. and M . P. Simonnin. J . Org. C/wtn., 1980, 45, 1270. A. Robert, M . T. Thomas, and A. Foucaud, J . Chem. Soc., Chem. Commun., 1979, 1048. G . Cavicchio, G. Gaudiano, and P. P. Ponti, Tctruhedron Lett., 1980, 21, 2333.

206

207

Ylides and Related Compounds

Ylidic adducts (6) have been prepared by the reaction of electron-deficient allenes with p h ~ s p h i n e swhereas ,~ the stable ylides (7) are formed in the reaction of tervalent phosphorus esters with dimethyl acetylenedicarboxylate.6 The cumulated ylides (lo), ( 1 I), and ( I 3) have been prepared by the action of the currently popular sodium bis(trimethylsily1)amide on the ylides (8), (9), and (1 2), re~pectively.~ It is gratifying to know that the well-known synthesis* of ylides from phosphines and carbenes is theoretically possible! The formation of arylmethylene ylides (14) from the photolysis of diary1 or aryl alkyl ketones in the presence of triphenylphosphine may or may not involve carbenes.'O Phase-transfer catalysis by crown ethers has been used to generate benzylphosphonium fluorides,l' which are known to be in equilibrium with the corresponding ylide and so undergo Wittig reactions under base-free conditions.12

R'O C

'\ /

/ \

C=C=C

C02R2

C02R2

+

R3,P

+

C02R2

R102C

R'02C

n m

(R'O),P + MeO,CC=CCO,Me

NaN(SiMe,),

Ph,P=CH-C-XMe

II

(8) X = 0 (9)x = s OEt

I

Ph ,P =C H -C =C R' R2

(12) ArCOR + 2Ph,P

C02Me

I

(R'O),P--C-CHCO,Me

(7)

+ NaXMe + HN(SiMe,),

(1O)X (11)X

= =

0

s

NaN(SiMe,),

hv

I

0R2

Ph,P=C=C=X

X

C02R2

Ph ,P =C =C=C

R'R2

(1 3)

Ph,PO + Ph,P=CArR

(14) R. Gompper and U . Wolf, Liebigs Ann. Chem., 1979, 1406.

li

I1 12

K . Burgada, Y . Leroux, and Y . 0. El Khoshnieh, Tetrahedron Lett., 1980, 21, 925. H . J. Bestmann and D. Sandmeier, Chem. Ber., 1980, 113, 274. A. J . Speziale and K . W. Ratts, J . Am. Chem. SOC.,1962, 84, 854. G . Trinquier and J . P. Malrieu, J . Am. Chem. SOC.,1979, 101, 7169. M. A . Fox, J . Am. Chpm. SOC.,1979, 101, 5339. G. Kossmehl and R. Nuck. Chem. Ber., 1979, 112, 2342. C i . 1'. Schiemenz, J . Becker, and J. Stockigt, Chem. Ber., 1970, 103, 2077.

208


Ph

Ph

Similarly, the addition of phosphines to cyclic perfluoroalkenes, e.g. ( 1 9 , is known to give phosphonium ylides,13 presumably by the mechanism shown. However, the most recent report l4 demonstrates that ylide formation is observed only when the carbanion is stabilized by p-fluoro substituents; e.g., (16). When a-fluoro-substitution exists, pentaco-ordinate phosphorus is formed (Scheme 1).

+ BU,P

CF,CF=CF,

-

C F , C F = C F ~ B ~ , F-

%

-

F

/

C=C

Ph'l

Ph'Ph

CF,CF,CFPB~,

Scheme 1

@-Fluoro-stabilizedylides (17) have also been generated in situ from triphenylphosphine and tetrakis(trifluoromethyl)-1,3-dithietan, and in the presence of aromatic or aliphatic aldehydes they give good yields of bis(trifluoromethy1)alkenes.l6 Fluoride-induced desilylation of (1 8) has been used to prepare methylenetriphenylphosphonium ylide in situ.ls

\

S

/

+ 2Ph,PO

2RCH=C(CF,),

IPh,b-CH,SiMe,

CsF

[Ph,P-CH,I

*

P

h

o

C

H

,

(18) 1s 14

l5 18

R. D. Howells, P. D. Van der Valk, and J . J . Burton, J . Am. Chem. SOC.,1977, 99, 4830. D. J . Burton, S. Shinya, and R. D. Howells, J . Am. Chem. SOC.,1979, 101, 3689. D. J. Burton and Y. Inouye, Tetrahedron Lett., 1979, 3397. E. Vedejs and G . R. Martinez, J . Am. Chem. SOC.,1979, 101, 6453.

209


Predictably, silyl substituents, as in (19), increase the thermal stability and reduce the nucleophilicity of 1-methyl-1-methylene-A5-phospholan (20) ; this can be generated from (19) by desilylation with Trimethyl(silylmethy1ene)phosphorane (21 ) has been prepared by the reaction of 2-chloroethylsilane with trimethylmethylenephosphorane,and its structure in the gas phase has been determined by electron diffraction.18 The first example of a bis(methylenephosphorane), e.g. (23), containing two terminal ylide groups has been prepared by the reaction of lithium bis(trimethy1sily1)methylenediphenylphosphine anion (22) with methylene iodide. l g However, the success of the method depends on the stabilization of (23) by the silyl groups rather than the method itself. The related di-ylide (25) and the mono-ylide (24) have been prepared as shown in Scheme 2. Both (24) and (25) react with sodamide to give coloured, crystalline sodium complexes (26) and (27).20

(19) R = SiMe, (20) R = H

M e 36-C cS i H

-

[Ph,P-C(SiMe,),] (22)

-

Li'

C,H,

Me,kH,SiH, CI-

CHJ,

Me P=CH,

Ph,P

(21)

+ Me,P' CI-

It

I1

C(SiMe,),

(Me,Si),C

(23)

The stable, symmetrically substituted ylide (30) has been prepared from the trisphosphine (28) via the carbanion (29), and its structure has been determined by X-ray analysis.21 Attempts to alkylate (28) directly led to cleavage of the C-Pbond.22 Reactions.--A ldehydes . In Wit t ig react ions of benzy I t r iary1phosphoni um y 1ides with acetaldehyde, increasing steric crowding at phosphorus leads to an increase The authors argue convincingly that this in the cis-trans ratio of the l7 l8

"')

22

33

H . Schmidbaur and H. P. Scherm, Z . Anorg. Allg. Chem., 1979, 459, 170. E. A. V. Ebsworth, D . W . H. Rankin, B. Zimmer-Gasser, and H. Schmidbaur, Chem. Ber., 1980, 113, 1637. R. Appel and G . Haubrich, Angew. Chem., Int. Ed. Engl., 1980, 19, 213. H . Schmidbaur, U . Deschler, B. Zimmer-Gasser, D. Neugebauer, and U. Schubert, Chem. Bey., 1980, 113, 902. H . H . Karsch, Z . Nuturforsch., Teil. B, 1979, 34, 117 1 (Chem. Abstr., 1980, 92, 42 052); H. H . Karsch, B. Zimmer-Gasser, D. Neugebauer, and U . Schubert, Angew. Chem., Inr. Ed. Engl., 1979, 18, 484. S. M . Nelson, M . Perks, and B. J . Walker, J . Chem. SOC.,Perkin Trans. 1, 1976, 1205. D. W. Allen and H . Ward, Tetrahedron Lett., 1979, 2707.

210

Organophosphorus Chrmistrj* CH,

Ph,P

/’

\

PPh, I(2X)

CH,

+ /

I

PhCH,

Ph,P

‘iPh,

PhCH,

PhCH,

I

Br-

H Ph,P

I

2Br-

H

PPh,

Ph,P

I

I

PhCH,

2\

PhCH,

(24)

iPh2

CHPh

(25)

(26) Reagents: i. PhCHzBr; i i , N a N H n ; i i i , PhxP-CH?

Scheme 2

*+

Me,PO. Li1

21- +

+

Me,P

I

supports a [ n Z a + n,,]cycloaddition mechanism (31) to give a cis-1,2-oxaphosphetan (32) directly, without involvement of betaine intermediates, since large steric effects from phosphorus would clearly favour the formation of the cisoxaphosphetan (32). A stereoselective synthesis of (Z)-c$-unsaturated aldehydes (34) is provided by the Wittig reaction of the ketal ylide (33),24 itself prepared from formylmethylenetriphenylphosphorane(Scheme 3). 24

H . J . Bestmann, K . Roth, and M . Ettlinger, Angew. Chem., I n r . Ed. Engl., 1979, 18. 687.

Ylides and Related Compoitrtds

21 1 Ar H\ \

c-c

Ph,P=CHCHO

H

\

H

'

C=C

R

/'

'CHO

H

c=c

IV.

v

+ Ar,PO

Br

I_ Ph$-cH=CHOEt

-

/

1.

II. 111

Ph,P=CH-CH

(OEt),

(33)

(34) [ > 9 5 % 2 ]

Reagent$: i, EtBr; i i , NaNHz; i t i , EtOH; iv, RCHO; v, 4-MeC6H4S03H

Scheme 3

Since polymer-supported Wittig reactions and phase-transfer-catalysed Wittig react ions have been reported, phase-transfer-ca tal ysed pol ymer-su ppor ted Wittig reactions should not come as a surprise! 25 Intramolecular Wittig reactions have been used in a variety of syntheses. Those involving 8-lactam antibiotics include (6R,7S)-l-oxa-l-desthiacephalosporins (35),26 7-0x0-3-mercaptyl-1 -azabicyclo[3 .2.O]hept-2-ene-2-carboxylates (36),27 optically active (5R)-2-penam-3-carboxylates(37),28 and a variety of 2-alkyl- and 2-aryl-substituted analogues (38) of thienamycin.2RBy carefully controlling the reaction conditions, a general method 3 0 of synthesis of lactones, ~ . g (39), . with rings of thirteen or more members from ketophosphonates has been developed (Scheme 4). A similar method (Scheme 5), under somewhat

RNH Me,C'O. Me1 H,O, BaCO,

0

I

CO,CMe,

CO,CMe,

(35)

S. D. Clarke, C. R . Harrison, and P. Hodge, Tetrahedron Lett., 1980, 21, 1375. C. L. Branch and M . J . Pearson, J . Chem. Soc., Perkin Trans. I , 1979, 2268. R . J . Ponsford, P. M. Roberts, and R . Southgate, J . Chem. SOC.,Chem. Commun., 1979, 847; A . J . G. Baxter, R . J . Ponsford, and R . Southgate, ihid., 1980, 429. M . Foglio. G. Franceschi, C. Scarafile, and F. Arcamone, J . Chem. Soc., Chpm. Commun., 1980, 70.

L. Cania and B . G . Christensen, Tetrahedron Lett., 1980, 21, 2013. G. Stork and E. Nakamura, J . Org. Chem., 1979,44, 4010.

212


R' 0*SRZ

oa+.H20Ac

CO,R'

R*o

CO,R

(36)

C0,(4-N0,C,H4) (38)

(37)

different conditions, has been used to synthesize the 'left-wing' of carbonolide B (40)and in an efficient synthesis of (+)-muscone (41) from oleic acid.31(See also the next Section, on Ketones).

Reagents: i, HMPT,THF; ii, Pr'OLi, THF; i i i , AcOH

Scheme 4 0

0

( M e O ) ! j A

6..;'

___) I

25'C

0

( M 0 e O ) * ! O

I

iii

___)

31

0

K. C . Nicolaou, S. P. Seitz, M. R. Pavia, and N. A. Petasis, J . Org. Chem., 1979, 44, 401 I .


213

Various dienes have been prepared by Wittig reactions of both saturateds2 and unsaturated 3 3 phosphoranes. The synthesis of the dienes (42) 34 and (43) 35 has been achieved by alternative routes. The highly stereoselective Wittig reaction of (E)-2-hexenylidenetriphenylphosphoranewith the lactol(44) is a key step in the synthesis of palitantin (45).36 4-Bromo-l,4-dienes (46), with the (E)-form predominating, have been prepared from (dibromomethy1ene)triphenylphosphonium ylide by alkylation with ally1 bromide followed by a Wittig reaction (Scheme R’O

\

C=C H/

/

R’

H

‘CHO

+

\

Ph,P=CHR’ I1

’

C=C

R2

/

H

+

Ph,P=CH (OR’)

‘CHO

H

OR2

3% 33 :j4

37

E. Piers and E. H . Ruediger, J . Org. Chem., 1980, 45, 1727. H. Duttrnann and P. Weyerstahl, Chem. Ber., 1979, 112, 3480. S. David and J . Eustache, J . Chem. SOC.,Perkin Trans. 1 , 1979, 2521. S. David and .I.Eustache, J . Chem. Soc., Perkin Trans. 1, 1979, 2230. A . Ichihara, M. Ubukata, and S. Sakamura, Tetrahedron, 1980, 36, 1547. R. H. Srnithers, J . Org. Chem., 1980, 45, 173.

8

214

Organophosphorus Chemistrev Ph36-CBr,

+ H,C=CH

--CH,Br

--+

Ph,b-CBr,CH,CH=CH,

Br-

i i . ii

RCH=CBrCH,CH=CH, (46)

Reagents; i, BuLi; i i , RCHO

Scheme 6

Triene syntheses include a quantitative yield of the iron complex (47)from a Wi ttig reaction of the corresponding aldehyde. Acetylenedicarbaldehyde mono(diethylacetal) (48)can be converted into unsymmetrical dienynes (49)by stepwise Wittig reactions3Por into cyclic tetraenes (50) via Diels-Alder and Wittig reactions (Scheme 7).40

O H C C E C C H (OEt), IV, I

111

(50) Reagents: i, Ph,P=CR'R';

ii, HC'OIH: iii, Ph,P=CR'R4;

IV,

Scheme 7

Several groups have investigated the structure and synthesis of the slowreacting substance of anaphylaxis (SRSA), possibly the major mediator in allergic asthma. The tetraenes (52) and (54) have been synthesized by the reaction of (Z)-non-3-enylidenetriphenylphosphoranewith aldehydes ( 5 1) and (53);40 the relative stabilities of (52) and (54) suggest that SRSA has the structure ( 5 5 ) rather than its (2E)-isomer. ( k )-5,6-0xido-7,9-trans-11,14-cis-eicosapentaenoic M 3g 40

J . Martelli, R. Gree, and R. Carrie, Tetrahedron Lett., 1980, 21, 1953; B . F. G . Johnson, J . Lewis, and G. R. Stephenson, ibid., p. 1995. A. Gorgues and A. le Coq, Tetrahedron Lett., 1979, 4825. A. Gorgues and A . le Coq, Tetrahedron Lett., 1979, 4829; R . Rokach, Y. Girard, Y . Guindon, J . G. Atkinson. M . Larue, R . N. Young. P. Masson, and G. Holme, ibid., 1980. 21, 1485.


21 5

C0,Et

C0,Et

+ P h , P = C H q CHO

+

-w

C,Hll

(52)

(51)

CO,Et

/

(54) R = C0,Et

(55) K =

"y"\o,H OH

acid (58), which is a possible precursor of SRSA, has been synthesized, using the Wittig reaction of (Z)-non-3-enyltriphenylphosphoranewith the aldehyde (56) as a key step41 and more directly with the epoxy-aldehyde (57).42 An alternative route through the aldehyde (60)and the dienyl ylide (59) gave (58) as a mixture of isomer^.^^^ 4 3 A number of vinylogous bipyridyls and biquinolyls have been prepared by a variety of routes involving Wittig reactions.44Worthy of mention are the use of glyoxal and a method involving arylation with 2-chloroquinoline, although the yields are poor (Scheme 8).

""1

OHC

m OSiMe, (56) H

OHC

C0,Me H (57)

41 42

43 44

E. J . Corey, Y. Arai, and C. Mioskowski, J. Am. Chem. SOC.,1979, 101, 6748. E. J . Corey, D. A. Clark, G. Goto, A. Marfat, C. Mioskowski, B. Samuelsson, and S. Hammerstrom, J . Am. Chem. SOC.,1980, 102, 1436. J . G. Gleason, D. B. Bryan, and C. M. Kinzig, Tetrahedron Lett., 1980, 21, 1129. P. Carsky, S. Hunig, 1. Stemmler, and D. Scheutzow, Liebigs Ann. Chern., 1980, 291.

216

Organophosphorus Chernistrj3

C0,Me

2HetCH2bPh, Het-C1

+ H,C=CHCH=PPh,

X-

C0,Me

* --+

Het(CH=CH),

Het

Het-CH,CH=CHhPh,

C1-

iiil

Het(CH=CH),Het

Het-CH=CHCH-PPh,

Reagents: i, NaOEt, EtOH, DMSO;ii, OHC-CHO; iii, PhsP=CHCH=CHz; iv, Het--CHO Scheme 8

Ketones. The detailed mechanism of the Wittig reaction continues to be an active area for speculation. Bestmann has provided further indirect evidence for involvement of the rearrangement (61) to (62) at pentaco-ordinate phosphorus in order to achieve an axial leaving X-Ray analysis confirms that the reaction of the cyclic phospha-allene ylide (63) with fluorenone gives the adduct (64), where the rearrangement of (61) to (62) is precluded. An interesting new

45

H . J. Bestmann, K . Roth, E. Wilhelm, R . Bohme, and H. Burzlaff, Angew. Chern., Inr. Ed. Engl., 1979, 18, 876.


217

R’

R’

\c=c H/

trans

\

/H ‘R2

H

’

c=c cis

/R2 ‘H

rationale for the cis-stereoselectivity in alkenes obtained from salt-free Wittig reactions has been put forward.46 The authors suggest that, under these conditions, the olefin may be formed by anti- rather than syn-elimination from (65). This assumes that the thermodynamically more stable trans-oxaphosphetan predominates in the reaction; in view of the contorted argument sometimes adopted to rationalize the predominance of the cis-oxaphosphetan, this is perhaps a point in favour of the new mechanism. Debate of the role of betaines and/or oxaphosphetans in the Wittig reaction continues. Schlosser has investigated the reaction of the betaine (66) with a further mole of base and f~rmaldehyde.~’ On the basis of similar deuterium distribution from deuteriated betaine and formaldehyde and from betaine and deuteriated formaldehyde, the equilibrium shown in Scheme 9, and hence the involvement of the betaine (67), have been postulated. One objection to this reasoning is the possibility of direct interconversion of phosphetans (68) and (69) via a bicyclic hexaco-ordinate phosphorus intermediate (70). 4H 4’

J . D. Thacker, M. H . Whangbo, and J . Bordner, J . Chem. SOC.,Chem. Commun.,1979, 1072. M . Schlosser and H . B. Tuong, Angew. Chem., I n t . Ed. EngI., 1979, 18, 633.

218

Organophosphorus Chemistry CI / H / eM' D,C-

I

i*

R,P-0

J

I I D,C-C-CH, I I LiO

HOCD,

/

OLi

(66)

'J

'

ph3p;

/Me

OLi

0-PR,

I

I

D,C-C-CH2

F+=

I

(69) (68)

\

C=CH,

1

Me OLi

Me

I

I

/

Me

\

D,C=C'

CH,OH /

\

Me

Reagents: i, Base; ii, DCDO; i i i , HCHO

Scheme 9

By analogy with the reductive elimination of vicinal benzoyloxysulphones, Lythgoe has suggested that the proportion of trans-olefin from Wittig and phosphonate reactions will be increased by chain branching adjacent to the double bond.48 This has been confirmed in several cases, and is probably a result of steric interaction promoting the dissociation of the erythro-betaine and hence increasing the formation of the fhreo-betaine. While cyclopropanone and cyclopropanone hemiketal (71) do not undergo the Wittig reaction, treatment of the hemiketal with methylmagnesium iodide converted it into a species, probably (72),which reacts with a variety of benzylidenephosphonium ylides to give a l k e n e ~ .However, ~~ 4-nitrobenzylidenetriphenylphosphorane and alkylidenephosphoranes d o not give the corresponding alkenes when allowed to react with (72), although in the latter case the betaine intermediates, e.g. (73), can be isolated. Intramolecular Wittig reactions have been used to prepare both five- and sixmembered rings. (Bromoacetylmethylene)triphenylphosphorane acts as a convenient cyclopentannelating agent for a wide range of enolates, e.g. (74), through alkylation and an intramolecular Wittig reaction.50 Full details of the synthesis of (-)-(S)-bicyclo[3.3.1]non-l(2)-ene (76), the first anti-Bredt compound with 48

4Q 50

P. J . Kocienski, B. Lythgoe, and I . Waterhouse, J . Chem. Soc., Perkin Trans. I , 1980, 1045. J . Salaun and A. Fadel, Tetrahedron Lett., 1979, 4375. H . J. Altenbach, Angew. Chem., Int. Ed. Engl., 1979, 18, 940.


OEt

OEt

(71)

0- Na'

219

(72)

0

0

n Br(75)

n (76) [27%]

a known absolute configuration, have been reported. The method uses an intramolecular Wittig reaction of (75) as a key step.51 A new, one-pot synthesis of 3-acyl-cyclohexa- 1 ,Cdienes is provided by the reaction of acylmethylenephosphonium ylides with electron-deficient d i e n e ~ The . ~ ~ proposed mechanisms are outlined in Scheme 10. The vinylphosphonium bicyclo-annulation outlined in Scheme 1 1 has been developed through a number of model studies and applied as the key step in the synthesis of trachyloban-19-oic acid (77).53The yields obtained are remarkably high, considering the alternative sites for attack by the ylide carbanion. Miscellaneous Reactions. A further report of the conversion of esters into branched alkenes (78) by reaction with phosphonium ylides includes conditions for improved yields from aliphatic esters and a broadening of the scope of the react i ~ n o-(Acy1oxy)benzyl . ~ ~ bromides react with phosphonium ylides to form chrom-2-enes in good yield,66presumably by the mechanism shown in Scheme 12. 51

52

53

54 55

M. Nakazaki, K. Naemura, and S. Nakahara, J . Org. Chem., 1979,44,2438. W. Flitsch and E. R. Gesing, Tetrahedron Lerr., 1979, 4529. R. M. Cory, D. M. T. Chan, Y.M. A. Naguib, M . H. Rastall, and R . M. Renneboog, J . Org. Chem., 1980, 45, 1852. A. P. Uijttewaal, F. L. Jonkers, and A. Van der Gen, J . Org. Chem., 1979,44, 3157. A. Hercouet and M. Le Corre, Tetrahedron L e f t . , 1979, 2995.

220

Organophosphorus Chemistrjj

1/

+

fO*Rz hPh,

I

concerted

0

y r 3

R'

- o;l +

Ph3PO

0 Scheme 10

Scheme 11

8 ,I

Me

@CHR' R1C0,R2 + Ph,P=CHR3

--+

Me' CO,H

K'C

\

CH,R3

(78)

(77)

a

CR'=PPh

CH,Br

OCOR'

ZPh,P=CHR'

aC

H OCOR'

+ Ph,kH,R2 Br-

Scheme 12

+

+ Ph,PO


22 1

Bestmann and his co-workers have thoroughly investigated the chemistry of cummulenylidene ylides (79);56-59 some of this chemistry is summarized in Scheme 13. The reactions of ketenylidenetriphenylphosphorane (80) and its

Nn:ph Ph,P=C=C=X

Ph

I

Ph‘N

Ph,P=CH-C-y

(79)X = O , S , NPh,

I

Ph

ir

I1

X

I

ArCH=CH-C-Y

I1

Y

I/

Reagents: i . P h N O ; i i , RCN C

Z ( Y = 0, S, or N P h ) ; iti, H Y ; iv, ArCHO

Scheme 13

dimer (81) with acid are shown in Scheme 14. With aryl acid chlorides, both (80) and (81) give the pyrone-derived salt (82). However, as shown in Scheme 14, the reactions with acid chlorides containing an a-hydrogen atom are more complex.

Ph,P=C=C=O

(80)

-

ArCO

\

ArCOCl

+/

,c=-c=o

Ph,P

-

Ar\

C

li

+/

Ph,P

C

P-

\

y=O

(82) Scheme 14 (part) 5u 57 5*

H. J. H. J. 2401. H. J. H. J.

8*

Bestmann, G. Schmid, a n d E. Wilhelm, Angew. C‘henr., fnt. Ed. Engl., 1980, 19, 136. Bestmann, G. Schmid, D. Sandmeier, a n d C. Geismann, Tetrahedron Lett., 1980, 21, Bestmann, G. Schmid, a n d D. Sandmeier, Chem. Ber., 1980, 113, 912. Bestmann a n d C. Geismann, Tetrahedron Lett., 1980, 21, 2 5 7 .

222

Organophosphorus Chemistrjp RiR2C.

(81) + R'R2CHCOCI

--w

n

( 8 3 ) + Ph,PO +

'CY-fo &\ PPh,

Scheme 14 (continued)

The reaction of the ester-stabilized ylide (84) with aryl isocyanates provides a simple synthesis of 1,3,9-triaza-anthracene derivatives (85).s0 3-Thioacetalphosphonium ylides (86) provide a new routes1 to P-functionalized ketones through alkylation, acylation, and the Wittig reaction (Scheme 15). N-Cyano-a-diazoimines (87) have been prepared from acylmethylenephosphoranes and cyanoazide.62 0 XH

(85)X = NArorO

n

n s\/s

Ph,P=CR'CH,-CR2

R 4CH =C

R' C H,-

s\

C R'

+ Ph3P0

(86)

'

4

R' R3C=CHCOR2 Reagents: i, RSX; i i , [ C O ( N O ~ ) ~ ] ( N HMeCN, ~ ) Z , H2O; Scheme 15

iii,

E h N ; iv, R4CH0

0RC=CHPPh,

RC-CH

N,CN

NCN,

N , N/

+

II II I

CN (87)

6" 62

L. Capuano. M. Bronder, K . Djokar, and I. Muller, Chem. Ber., 1980, 113, 395. H. J . Cristau, J . P. Vors, and H . Christol, Tetrahedron Lett., 1979, 2377. B. Arnold amd M . Regitz, Tetrahedron Lett., 1980, 21, 909.


223

With a view t o the synthesis of thioketens, the reactions of phosphonium ylidess3 and of phosphonate carbanionsePwith carbon disulphide have been investigated. In the ylide reaction,63 decomposition of the initial adduct (88) gives a variety of products, and attempts to trap (with amines or azomethines) any thioketens that were formed gave the expected products; however, the authors suggest that they are derived from the betaine (88) rather than from thioketens. Phosphonate carbanions give similar adducts (89), which eliminate an available hydrogen atom (R2or R3= H) t o give (90). However, neither (89) nor (90) eliminates thiophosphate t o give t h i o k e t e n ~ .Reactions ~~ of (2,2-diethoxyviny1idene)triphenylphosphorane with carbon disulphide and with carbon dioxide give the adducts (91) and (93); on heating, these rearrange t o the stable ylides (92) and (94).66 The stability of the ylide is important in reactions with sulphur monoxide;66 moderately stable ylides, e.g. ( 9 9 , give sulphines.

Ph,P=CR'R2

-

O3 O4

65

"3'

-

+ CS,

p.

-'---f.i

E. Schaumann and F. F. Grabley, Liebigs Ann. Chem., 1979, 1702. E. Schaumann and F. F. Grabley, Liebigs Ann. Chem., 1979, 1715. H. J. Bestmann and R. W. Saalfrank, J . Chem. Res. ( S ) , 1979, 313. S . F. Bonini, G. Maccagnani, G. Mazzanti, P. Pedrint, and P. Piccinelli, J. Chem. Suc., Perkin Trans. I , 1979, 1720.

224

Organophosphorus Chemistry Ph,P=CR'R2

+ [SO]

--+

R'R2C=S0

+ Ph,P

(95) R'R' = Ph or R' = RZ = Ph

A general method of preparation of pyranylidene dimers (97) has resulted from attempts to prepare unsymmetrical dimers (98) from a Wittig reaction of thiopyran-4-thione with the ylide (96).s7 The Wittig olefination of thiocarbonyl groups adjacent to nitrogen has been investigated.68 Schmidbaur's group has prepared a variety of phosphonium ylide-borane adducts (99) and investigated their spectroscopic proper tie^.^^ The sterically hindered ylide (100) is known to be extremely thermally labile; however, the corresponding adduct (101) melts at 229 "C without decomposition. A number of transition-metal complexes, e.g. (lO2),'* (103),'l (104),72 and ( 109,' have been prepared.

Ph[

APh3 0,jPh

---+

' 0 + 2Ph,P

Ph

R1,P=-CHR2

Ph

+ H,B-OEt,

-+

Ph

Ph

R',6-CHR2-BH3

(99) BU'

,LCH,BH,Me g-CH, (101)

(CO),CrCH,hh, (102)

67

6s 63 70

7L 72 73

CH,-6Me2

I H,B

-

\+

\

\-/ /M\

Me,P -CH,

-

BH,

+/

CH2-PMe,

(103) M = Ni, Pd, or Pt

G. A. Reynolds, C. H. Chen, and J . A. Van Allan, J. O r g . Chem., 1979, 44, 4456. A. Gossauer, F. Roessler, H. Zilch, and L. Ernst, Liebigs Ann. Chem., 1979, 1309. H. Schmidbaur, G. Miller, and G. Blaschke, Chenr. Ber., 1980, 113, 1480. L. Knoll and H. Wolff, Chem. Ber., 1979, 112, 2709. G. Muller, U. Schubert, 0. Orama, and H. Schmidbaur, Chem. Ber., 1979, 112, 3 3 0 2 . H. Schmidbaur, G. Blaschke, and H. P. Scherm, Chem. Ber., 1979, 112, 3311. J. M. Bassett, J. R. Mandl, and H. Schmidbaur, Chem. Ber., 1980, 113, 1145.


225

2 Reactions of Phosphonate Anions PO-Activated olefin synthesis has been r e v i e ~ e d . ' ~ The use of lithiated diethyl [ 1-(trimethylsilyloxy)alkyl]phosphonates (106) as equivalents of acyl carbanions has been further i n v e ~ t i g a t e d76. ~Alkylation ~~ of (106), followed by hydrolysis, gives the ketones (109); however, in certain cases, complications arise through the Wittig rearrangement of (107) to ( 108).75 The reaction of (106) with aldehydes or ketones 76 generally gave a-hydroxy-ketones, as shown in Scheme 16, although the phosphonate (1 10) could be isolated from 0

II

RICH P(OEt),

I

Pr',N1

I

0''

0

II

R'C-P(OEt),

I

OSiMe,

F=+

OSiMe,

(1 06)

.Li.

I R'C-

"0

I1

P(OEt b2

I

SiMe,

(107)

( 1 08)

I.

room temperature

0

I1

R'R'CP(OEt),

NaOH

I

OSiMe,

R'R2C0 ( 109)

(106; R' = Ph) % R' R2C-0-Li' iii)R1

= H.R' = A r l

0

R'R'C-OSiMe,

iiil

PhCOCR'R'

II

(EtO),PCPhOSiMe,

I

I

OH

ArCHOH ( 1 10)

Reagents: i, LiNPr',, THF, at -60 " C ;ii, R1R2C0, at - 1 0 0 " C ;iii, H J O +

Scheme 16 74

75 76

B. J . Walker in 'Organophosphorus Reagents in Organic Synthesis', ed. J . I . Cadogan, Academic Press, London, 1980, p. 155. M . Sekine, M. Nakajima, A. Kume, and T. Hata, Tetrahedron Lett., 1979, 4475. R. E. Koenigkramer and H . Zimmer, Tetrahedron Lett., 1980, 21, 1017.

2 26 Organophosphorus Chemistry reactions with aromatic aldehydes. The addition of elemental sulphur to phosphonate carbanions provides a general route t o a-phosphoryl thiols (1 11) and, through their alkylation, the sulphides ( I l2)." The latter compounds can act as equivalents of acyl anions in that their anions react with aldehydes to give (1 13), which are readily hydrolysed to the substituted ketones ( 1 14) (Scheme 17). 0

I1 (EtO),PCH,R1

-

0

0

I1

II (EtO),PCHR'SH

A (EtO),PCHR1SR2 (112)

(111)

R3CH,COR1

2

R3CH=C

(1 14) Reagents: i, BuLi, T H F ; 1 1 , Sn, at - 2 0 i C , RSCHO; vi. TiC14, H.0

III,

H ;

I\,

/ R'

( 1 13) 'RS'

R2X, NaOH, PhH. R4N+ CI : v,

Scheme 17

The use of lithium hexamethyldisilazide at low temperature, rather than sodium hydride, as a base in the reaction of the phosphonate ( 1 15) with isobutyraldehyde (Scheme 18) gave a much higher yield of diene and a higher proportion of the C0,Et

I

d'

C0,Et

C0,Me

I

I

CHMe, ( 1 15)

( 1 16)

Reagents: i,(TMS)zNLi.THF,at -78 "C;ii, Me2CHCH0,at - 4 0

C

Scheme 18

(E,E)-isomer (1 16).?!jPotassium fluoride can act as a mild base in PO-activated olefin synthesi~.'~ A mixture of vinylphosphonate and alkene (1 17) was obtained, but the use of the fluoride dihydrate and phase-transfer catalysts gave almost exclusively ( 1 17). Phase-transfer catalysis, by tetra-alkylammonium salts, of reactions of phosphonate anions ( I 18) with lactols leads t o improved yields and reproducibility.* O Cathodic reduct ion of diet h y1 t r ichloromet h yl p hosp honate (119) has been used t o generate the corresponding carbanion, which, in the presence of carbonyl compounds, gives I , 1 -dichloroalkenes in moderate yield.81 77 78 79

8" 81

M. Mikolajczyk, S. Grzejszczak, A. Chefczynska, and A . Zatorski. J. Org. Chrm., 1979, 44.

2967. W. R. Rousch, J. Am. Chem. SOC.,1980, 102, 1390.

F. Texier-Boullet and A. Foucaud. Terrahedron Lett., 1980, 21, 2161. B. M. Frost, G. T. Rivers, and J. M. Gold, J. Org. Chem., 1980, 45, 1835. F. Karrenbrock, H. J. Schafer, and I. Langer, Tetrahedron Leu., 1979, 2915.


227

0

II (EtO),PCH,R

0 + PhCHO

KF

DMF-

I/

( R = CN or C0,Et)

(1 17)

@

R

+ PhCH=CHR

(EtO),PCR=CHPh

cc

0

I1 Na+

0 + (MeO),wHCO,Me

Me,SO

7 (n-C,H,,),N Br-

R

(118)

OH

0

Aromatic and aliphatic aldehydes (but not ketones) can be converted into the corresponding enamines through olefination with (N-morpholinomethyl)diphenylphosphine oxide anion.82Previous attempts to use the analogous phosphonate anions have been only partially successful. Olefination with 2-sulphonylmethylphosphonate carbanions has been used to prepare both racemic and optically active vinylsulph~xides.~~ a[l-Unsaturated sulphonic acid derivatives ( 1 20) have been prepared from the corresponding phosph~nate.~~ An allene synthesis that is initiated by PO-activated carbanions has been used to prepare optically active allenes from ketens and the optically active phosphinate (121).85Enantiomeric excesses obtained are in the range 8-23%, and the mechanism of the reaction is discussed in terms of the thermodynamically most stable trigonal-bipyramidal intermediate. 0

II

+ R'CHO

(R'O),PCH,SO,R'

Ph

R'R2C=C=0

+ MeO'

\p/

0

82

83 84 85

BuLI. THF

-

R'

'CHC0,Me (121)

-

Na+

R'

R3CH=CHS0,R2

\

/

/

\

c=c=c

H

C0,Me

Ph

+

Me0

\ /o

/pie Na+

N . L. J. M. Broekhof, F. L. Jonkers, and A. Van der Gen, Tetrahedron Lett., 1979, 2433. R. W. Hoffman, S. Goldmann, N. Maak, R. Gerlach, F. Frickel, and G. Steinbach, Chem. Ber., 1980, 113, 819. M. Fild and H. P. Rieck, Chem. Ear., 1980, 113, 142. S. Musierowicz and A. E. Wroblewski, Tetrahedron, 1980, 36. 1375.

228


Olefination involving dimethyl diazomethylphosphonate ( 1 22)H6has been extended to reactions with dialkyl and cyclic ketoness7 Similar reactions with aldehydes or aryl alkyl ketones gave acetylenes (Scheme 1 9),87,88 presumably 0

0

il

II

(MeO),POK + [KC-N,]

(MeO),PCHN, + R,CO

Reagents: i, KOBu' at

~

78°C; ii.

0

Scheme 19

through rearrangement of the carbene (123), although attempts to trap (123) were unsuccessful. Reactions with cyclic or dialkyl ketones in the presence of alkenes gave moderate yields of alkylidenecyclopropanes, e.g. (l24), and so provide good evidence for the intermediacy of (1 23). A similar reaction, using nucleophiles as trapping agents, provides a novel route to aldehydic enol ethers and enamines (Scheme 20).89The more conventional use of the phosphonate reagents 0

II (MeO),PCHN,

+ R',CO

-

R'2~ =cH 0R' I y

[R',C=CN,] l h

R',C =CH N R32 Reagents: i. ButOK: ii. R 2 0 H : iii, R"NH

Scheme 20 ( 125) in the synthesis of enol ethers, and hence one-carbon annelation of ketones to aldehydes, has been further i n v e ~ t i g a t e d .9~1 ~Predictably, , the lithium alkoxides ( I 26) required prolonged heating before undergoing elimination, and the alternative procedure of isolation of the conjugate acid of (126) and treatment with potassium t-butoxide gave much shorter reaction times, although similar yields (Scheme 21 ). Individual geometrical isomers of vinyl ethers can be obtained by separation and base-induced decomposition of the diastereoisomeric phydroxy-phosphine oxides ( 127) and (1 28). 9 1 The p-hydroxy-phosphine oxide procedure for conversion of epoxides into alkenes and for inversion of olefins has been used for the synthesis of lockedtwist (1 3 1) and locked-chair trans-cyclo-octenes ( 1 32),92 through separation of 86

87 88 89

90 91

92

E. W. Colvin and B. J. Hamill, J. Chem. Soc., Perkin Trans. I , 1977, 869. J. C. Gilbert, U. Weerasooriya, and D. Giamalva, Tetrahedron Lett., 1979, 4619. J . C . Gilbert and U. Weerasooriya, J . Org. Chem., 1979, 44, 4997. J. C. Gilbert and U. Weerasooriya, Tetrahedron Lett., 1980, 21, 2041. A. F. Kluge and I. S. Cloudsdale, J . Org. Chem., 1979, 44,4847. C. Earnshaw, C. J. Wallis, and S. Warren, J . Chem. SOC.,Perkin Trans. I , 1979, 3099. P. F. Newton and G . H. Whitham, J . Chem. SOC.,Perkin Trans. I , 1979, 3067.

Yiides and Related Compounds

229 0

II

0

II

(R'O),PCHOR~

(R~O),PCH,OR'

\

J&

CR3R4

/

(1 25)

(R3 =

-

0

R3R4C=CHOR2

1

Li' -0

0

Li'

R3R4CHCH0

,CH,CH,OMe, or SiMe,Bu') 0

It

Ph,P

0

I1

0

iii

J.

(126)

/?

+ (R'O),P : \.

Ph'PCHRWMe

,OMe ' C h ~

I

-%

Ph,P

+

P

R3/7\

OH

; ' ? I

R4

( 1 27)

,OMe '&R2

I

C

\OH

R3 (1 28)

Reagents: i, LiNPrk, T H F ; ii, R 3 R T O ; iii, H:10 Scheme 21

the diastereoisomers (1 29) and ( 1 30) (Scheme 22). A related approach has been used to obtain both enantiomers of trans-cyclo-octeneby resolution of the corresponding #I-hydroxy-phosphineoxides as their ( - )-menthoxyacetic esters ( 1 33) and (1 34) and base-induced decompo~ition.~~ The optically active cyclo-octadiene ( 1 35) and epoxy-olefin (1 36) were similarly prepared. However, the method was not satisfactory for the synthesis of optically active locked-twist (1 37) and lockedchair trans-cyclo-octadienes(1 38); these were prepared 9 2 by a method analogous

e--H H

(131)

H (132)

Reagents: i, LiPPhz i i , MeCOZH; i i i , HzOe; iv. NaH. THF

Scheme 22 93

P. F. Newton and G . H. Whitham, J . Chem. Soc., Perkin Trans. I , 1979, 3072.

230


to that shown in Scheme 22. The configurations of ( 1 37) and ( 1 38) were unambiguously established by conversion into (139) and (140) respectively, since the former is optically active while the latter has a plane of symmetry. Intramolecular olefination, using a phosphonate, has been applied in a number of syntheses; for example, ( k )-4,5-deoxymaysine (141) 94 and maysine ( 142).95 Treatment of the phosphonate (143) with potassium t-butoxide gives the enone ( 144), presumably via a retro-aldol reaction followed by olefination. 90 The trans ring-junction in (144) is thought t o arise through stereoselective protonation of the aldehyde enolate from the side opposite to the adjacent methyl group, and the cyclization is a key step in the synthesis of ( k )-helenalin. A similar cyclization is involved in the synthesis of cyclopent-2-en-1-ones frQm ketone enolates

(133)

( 134)

-0 Me

R =

I

CHMe,

H

I" 94 95 98

A. I . Meyers, D. M . Roland, D. L. Comins, R. Henning, M. P. Fleming, and K . Shimizu, J . Am. Chem. Suc., 1979, 101, 4732. A. I . Meyers, D. L. Comins, D. M . Roland, R . Henning, and K . Shimizu. J . Am. Chrm. Suc., 1979, 107, 7104. M. R. Roberts and R . H. Schlessinger, J . Am. Chern. Suc., 1979, 101, 7626.


23 1

H

I

( 1 4 1 ) X = -C

yC-

(142) X = -C/

I

A

Me

Me 0

@

0-

I ,CH

I1

CH,P(OR

Bu'O

Bu'd

(143)

H

0

II

,CH,P(OR),

Me

J

that is shown in Scheme 23 97 and in annelation reactions using N-ethyl(diethy1phosphono)methylketenimine (1 45).s8 0

0

I1

OEt

I

(MeO),PCH =CCH,Br

*

II

??

CH,COCH,P (OMe),

+ (MeO),P

Reagents: i,

; ii, H,O', acetone; 111, NaH, DME

[ 74% overall)

Scheme 23 97 98

E. Piers, B. Abeysekera, and J . R. Schaffer, Tetrahedron Lett., 1979, 3279. J . Motoyoshiya. T. Enda, Y . Ohshira, and T. Agawa, J . Chem. Soc., Chem. Commun., 1979. 900.

232

Organophosphorus Chemistrj, 0

II

to),P,

( F:

C=C=NEt Me'

+

0 CHO

Na'

(145)

L

NEt

J

As might be p r e d i ~ t e d phosphonate ,~~ anions derived from imines undergo, probably stepwise, cycloaddition reactions with activated alkenes to give mixtures of pyrrolidines and A'-pyrrolines via ( 146).loo The reactions of lithium, silver, and mercury salts of diazomethylphosphoryl carbanions with a wide range of electrophiles have been investigated,'O' and found t o depend to some extent on the nature of the metal (Scheme 24). Li+ ( Et O),P -C H R' -N =CR'R3

+ R4R5C=CR! C0,Et

-

(Et0),P Li+

The autoxidation of carbanions derived from diphenyl {aryl[(4-nitrophenyl)amino]methyl}phosphonates(147) leads to the formation of the corresponding aroyl anilides in moderate yield.lo2 Optically active methylphenylcyclohexylphosphinesulphide undergoes or-metallation with retention a t phosphorus, as demonstrated by its conversion into carbethoxymethyl(pheny1)cyclohexylphosphine sulphide ( I 48). lo:) T. Kauffrnan, Angcw. Chem., I n t . Ed. Engl., 1974, 13, 627. A. Dehnel and G. Lavielle, Tetrahedron Lett., 1980, 21. 1315. l o l M. Regitz, B. Weber, and U . Eckstein, Liebigs Ann. Chem., 1979, 1 0 0 1 ; M. Regitz. A . Heydt, and B. Weber, Angew. Chem., I n t . Ed. Engl., 1979, 18, 531. l o 2 H . Zirnmer. R . E. Koenigkrarner. R . L. Cepulis, and D. M. Nene. J . Org. Chem., 1980, 45, 2018. l o 3 F. Mathey and F. Mercier. Tetrahedron Lett., 1979, 3081. 99

10"

Yiides and Related Compounds

23 3

0 R'*P-

CCPh,

II

R2P-CBr

I1

Reagents: i, PhCOBr; ii, BrCN; iii, Ph,CX; iv,

R* Scheme 24 0

'I

(PhO),PCHArNH O N 0 2

,CO,Et

(-)-GI 3 Selected Applications in Synthesis

Pheromones.-A variety of mono-olefinic pheromones ( 149) have been prepared that are stereospecifically ( E ) , by alkylation of diethyl allylphosphonate anions followed by reduction with lithium aluminium hydride (Scheme 25). l o 4 The silazide technique [the use of sodium bis(trimethylsily1)amide as the base for generation of an ylide] has been used to synthesize stereoselectively the insect sex attractants (150), (151), and (152),lo5the alkyl-branched analogues (153),lo6 and (5Zb5-tetradecadiene (1 54).lo7 ( 1 32)-13-0ctadecanal ( 1 56; R = CHO), a component of the sex attractant of' the rice stem borer, has been synthesized from a Wittig reaction of pentylidenetriphenylphosphorane with the aldehyde (1 5 9 , followed by reduction and oxidation. l o 8 104 105

106 107

108

C. Canevet, T. Roder, 0. Vostrowsky, a n d H. J . Bestrnann. Chem. Ber., 1980,113. 1 1 15. H . J. Bestmann, T. Suss, a n d 0. Vostrowsky, Tetrahedron Lett., 1979, 2467. H. J . Bestmann, P. Rose], a n d 0. Vostrowsky, Liebigs Ann. Chem., 1979, 1189. H . J. Bestmann, T. Brosche, K. H. Koschatzky, K. Michaelis, H. Platz, 0. Vostrowsky, a n d W. Knauf, Tetrahedron Lett., 1980, 21, 747. H. J. Bestrnann, R . Wax, a n d 0. Vostrowsky, Chem. Bey., 1979, 112, 3740.

234

Organophosphorus Chemistry 0

I1 (E tO),PCH ,CH =CH R II

(EtO),PHo I

I

5 RCH =CH -CH (CH,) ,OTH P

liii-"

H

I

RC H,C =C(CH,), OCOMe

I

H (149) Reagents: i, BuLi; ii, Br(CHz),OTHP; iii, LiAIH4; iv, HsO'; v, Ac2O. pyridine

Scheme 25

et?

H,C=CH-C

(CHJ,OCOMe (150)

H

=C(CH,),OCOMe H

(151)

H H R'R'CH(CH3, C=C(CH,), OCOMe ( 1 5 3 ) n = 0, 1 , 2 , o r 3 H H Me(CH3,C-C(CHz),CH=CH, (154)

Ph3P=CH(CH3,Me

+ OHC(CH3, ,CO,Me (155)

*

Me(CHzOCHJ,,R (1 56)

Prostaglandins.-The ylide (1 57) and phosphonate (15 8 ) continue to be widely used in prostaglandin 110 The formation of (159) by these methods presents a rare example of isomerization of a double bond in the Wittig reaction.llo The ylide carboxylate (160) has been used to introduce the (2)-heptenoic acid side-chain in syntheses of prostaglandin A,, l1 9-deoxa-9,lO-dehydroprostaglandin D2,lI2 1Zalkyl analogues of prostaglandin A2,113 (+_ )-prostaglandin F2a,114 and 10-fluoroprostaglandin F z a methyl ester.11KThe reaction 109 110

111

112 119

114 115

P. A. Zoretic, F. Barcelos, J. Jardin, and C. Bhakta, J. Org. Chem., 1980, 45, 810; E. J. Corey, J. W. Ponder, and P. Ulrich, Tetrahedron Lerr., 1980, 21, 137. A. G. Caldwell, C. J. Harris, R. Stepney, and N. Whittaker, J. Chem. SOC.,Perkin Trans. I , e.g.

1980,495.

M. A, W. Finch, T. V. Lee, S. M. Roberts, and R. F. Newton, J. Chem. Soc., Chem. Commun., 1979, 677. S . M. Ali, M. A. W. Finch, S. M . Roberts, and R. F. Newton, J. Chem. Soc., Chem. Commun., 1979, 679. C . B. Chapleo, S. M. Roberts, and R. F. Newton, J. Chem. SOC.,Chem. Commun., 1979, 680.

R. F. Newton, D. P. Reynolds, N. M . Crossland, D. R. Kelly, and S. M. Roberts, J . Chem.

Soc., Chem. Commun., 1979, 683.

P. A. Grieco, E. Williams, and T. Sugahara, J. Org. Chem., 1979, 44, 2194; P. A. Grieco, T. Sugahara, Y. Yokoyama, and E. Williams, ibid., p. 2189.


235 0

0 (159)

Ph,P =CH (CH,),CO;

Na'

I

t

,

,

(160) Ph,P=CHCH=CHCO,Me (163)

OR

OR

(161) R = R,Si (162) R = H

failed with the ketone (161), apparently because of enolization; however, the reaction of the unprotected ketone (1 62) with an excess of ylide gave the expected alkene. l6 A new method of formation of a side-chain is provided by Wittig reactions of the allylic ylide (1 63) followed by h y d r ~ g e n a t i o n . ~ ~ ' A Wittig reaction with methoxymethylenetriphenylphosphorane has been used to synthesize the diene (164) as a mixture of isomers en route to aromatic prostacyclin analogues. 11* MeOCH-CH

OHC* !

I

+ Ph,P=CHOMe

7 DMSO

* H-tJ.R

Carbohydrates.-The Wittig reaction of the p-D-ketose (165) with methoxycarbonylmethylene ylide required reaction in acetonitrile at 160 "C and 125 p s i . , and gave (166), presumably uia the expected alkene.l19 The formation of vinyl sulphides (1 69) and sulphoxides (168) through olefination of aldehydes, e.g. (1 67), by phosphonates is a key step in a new synthesis of 2-deoxy-~-ribosefrom glucose. O D. R. Morton, Jr., and F. C. Brokaw, J . Org. Chem., 1979, 44, 2880. R . D. Little and L. Brown, Tetrahedron Lett., 1980, 21, 2203. 1 1 * K . Shimoji and M. Hayashi, Tetrahedron Lett., 1980, 21, 1255. l l @ T. F. Tam and B. Fraser-Reid, J . Org. Chem., 1980, 45, 1344. 12" J . R . Hauske and H. Rapoport, J . Org. Chem., 1979.44, 2472. 116 117

236


R

0

CHO (167)

x

h

CH-CHSPh

It

X

(168) X = 0 (169) X = lone pair

Carotenoids.-The chromophore (172; K = H), containing the cis-pentaene system found in phytofluene (172; R = Me,C-CHCH,) from tangerine tomatoes, has been synthesized, using phosphine-oxide-based olefination (Scheme 26).121 Formation of the tetraene (170) takes place with complete preservation of stereochemistry of double bonds and 98 % (E)-olefination. In the second olefination step the mixture of erythro- and threo-p-hydroxy-phosphineoxides is isolated and separated by chromatography. Decomposition of the erythro-isomer ( 171 ) with sodium hydride gave the polyene (172; R = H), which showed spectral data closely related to those found in natural 15,9’-di-cis-phytofluene. The phosphorane (173) has been used to synthesize the extremely labile retinoid epoxide (174).’?‘ Non-benzenoid Aromatic Compounds.-The d icarbanion of the bisphosphonate (175) has been used to prepare a series of CH,-bridged [4n+ 2lannulenes (1 76), ( 1 77), and (1 78) by a building-block approach (Scheme 27). lZ3 Tetrabenzo[a,c,g,i]cyclododecene ( 1 79) and hexabenzo[d,f,jk,o,g,uv]dodecalene (180) have been prepared in low yield by multiple phosphonate cyclizations.124 121

122

123 12.1

J . M . Clough and G . Pattenden, Tetrahvdron Lvtt., 1979, 5043. D. Davalian and C . H. Heathcock, f. Org. Chom., 1979, 44, 4988. E. Vogel, H. M. Deger, J . Sombrock, J. Palm, A. Wagner, and J. Lex, Angew. Chem., In[. Ed Engl.. 1980. 19, 41. 1. Agranat, M . Rabinovitz, and W.-C. Shaw, J . O r g . Chem., 1979, 44, 1936.

Reagents: i , BULI, at

V.

MeO,C, 78°C; 11,

--

&

Carbon-13. Carbon-13 chemical shifts are at present considered to be one of the best probes into electronic effects of organic molecules. Calculations of CR and GI constants for the anilides and phenyl esters (10; X = O or NH) indicate that the electronic effects operating in phosphoryl molecules can be described in

terms of a variable degree of P-0 p,-d,, back-donation, competing donation effects from neutral atoms bearing unpaired electrons being of lesser importance.1 8 A 13C n.m.r. study of pyridoxal 5'-phosphate oxime has also been reported.20 Hydrogen-1. The 'H magnetic shielding constants for PH, and PMe, have been calculated and the separate contributions of the lone pairs of electrons estimated.21 Wide-line 16 MHz lH n.m.r. of insoluble crystalline butadiene-PCI, adducts has been used to investigate molecular mobility.22

Equilibria, Shift Reagents, and Liquid Crystals.-Phosphorus-carbon diad taut+ + omerism (Ph2P-CHEPPh, + P h 2 P H 4 E P P h , ) 2 3 and a new type of triad tautomerism involving phosphoryl migration 24 have been studied by n.m.r. In addition to a further example of keto-enol tautomerism e.g. (11),25 n.m.r. investigations revealed an interesting thiol tautomer (12), which is present in solutions of thiophosphonic sulphonamides.2s Me

Me

/N-N

\

SH

O H ( 1 1) 19 20

21 22

23 24

25 26

I

R,P=NSO,Ar (12)

N-NMe Me (1 3)

T. A. Modro, Phosphorus Sulfur, 1979, 5 , 331. T. Korpela, J . Lundell, and E. Makinen, Org. Magn. Reson., 1979, 12, 376. R. M. Aminova, M. B. Zuev, and I . D. Morozova, Izc. Akad. Nauk SSSR, Ser. Khim., 1979, 2190.

S. V. Fridland, V. S. Minkin, A . I. Efremov, E. S. Nefed'ev, and B. D. Chernokal'skii, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 876 (Chem. Abstr., 1979, 91, 73 816). T. A. Mastryukova, I . V. Leont'eva, and I . M. Aladzheva, Dokl. Akad. Nauk SSSR, 1979, 247, 866 (Chem. Ahstr., 1979, 91, 192 533). M. G. Zimin, M. M. Afanas'ev, and A. N. Pudovik, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 2323 (Chem. Absrr., 1980, 92, 110 306). A . I. Razumov, E. A. Krasil'nikova, T. V. Zykova, and 0. L. Nevzorova, J . Cen. C'hPm. USSR (Engl. Transl.), 1979, 49, 469 (Chem. Abstr., 1979, 91, 20 61 1). L. Almasi, R . Popescu, and L. Paskucz, Reo. Roum. Chim.. 1979,24, 3 (Chem. Abstr., 1979, 91, 19 523).

243

Physical Methods

Lanthanide shift reagents have been used in studies of the stereochemistry of cyclophosphamide and rigid model analogue^,^' and of derivatives of trishydrazinediyldiphosphine ( 13).2 8 The association constants of butylphosphonium-ferricyanide ion-pairs have been calculated from 6~ displacements.29 The n.m.r. spectra of phosphacymantrene in a liquid crystal gave H-H and P-H direct dipolar coupling constants, which were used to determine the H-H and P-H distances.30

Variable-temperature Studies.-Pseudorotatiort and Restricted Rotation. N.m.r. studies of cyclic phosphoranes possessing four P-C bonds, e.g. (14), are in best accordance with t.b.p. geometries pseudorotating by a turnstile m e ~ h a n i s m . 3 ~ The equilibrium geometries and harmonic force fields of PH5 have been calculated by an ab initio method which included electron correlation. The barrier to Berry pseudorotation was estimated to be 2 kcal m 0 1 - l . ~There ~ have been some further studies of tri- and tetra-oxypho~phoranes,~~ and also of some tri- and tetra-fluorophosphoranes ( 15),34 where pseudorotation is combined with restricted rotation about the P-Y bond when Y is F2PNH35or MeS.36 One of the (13C)carbonyl resonances observed in the spectra of tribenzoylphosphine 37a has been shown to be an impurity, and thus the n.m.r. spectrum shows no evidence for restricted P-C rotation.38 Further MO calculations predict that the P-C rotational barrier in triformylphosphine is less than 6 kcal mol-l and that the inversion barrier is ca. 14 kcal m 0 1 - ~ . ~Hindered @ rotation about the P-C bonds of aryldimesitylphosphines leads not only to non-equivalent ortho- and metacarbon atoms in the aryl rings but also t o different geminal P-C MIND0 calculations have been shown t o be a considerable advancement for estimating the ground-state geometries and rotational barriers of aminop h o ~ p h i n e s The . ~ ~ P-N rotational barrier in phosphinamide, H2P(0)NH2, has

(14)

(15)

D. W. White, D. E. Gibbs, and J. G. Verkade, J. Am. Chem. Soc., 1979, 101, 1937. 9H R. D. Kroshefsky and J. G. Verkade, Phosphorus Suvur, 1979, 6, 397. 2 8 S. Papp and P. Kvintovics. M a g y . Kem. F o b . , 1979, 85, 202 (Chem. Abstr., 1979, 91, 90 946). C. L. Khetrapal, A . C. Kunwar, and F. Mathey, J. Urganomet. Chem., 1979, 181, 349. 31 H. Schrnidbaur and P. Holl, Chem. B w . , 1979, 112, 501. 3 2 W. Kutzelnigg, H. Wallmeier, and J. Wasilewski, Theor. Chim. Acta, 1979, 51, 261. 33 Yu. Yu. Samitov, Chem. Abstr., 1979,91,56 206; J. Brierley, J. I. Dickstein, and S. Trippett, Phosphorus Sul/ur, 1979, 7 , 167. 3 4 R. K. Marat and A. F. Janzen, Inorg. Chem., 1980, 19, 798. 35 D. W. H. Rankin and J. G. Wright, J. Chem. SOC.,Dalton Trans., 1979, 1070. 36 R. G. Cavell, K. I . The, J. A. Gibson, and N. T. Yap, Inorg. Chem., 1979, 18, 3400. s7 ( a ) ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1979, Vol. 10; ( 6 ) ihid., 1974, Vol. 5 . 3 8 D. Kost, F. Cozzi, and K. Mislow, Tetrahedron Lerr., 1979, 1983. 3t) D . A . Dougherty and K . Mislow, Tetrahedron L e t t . , 1979, 2321. 40 V. V. Negrebetskii, A. I. Bokanov, N. A. Rozanel’skaya, and B. 1. Stepanov, J. Gen. Chem. USSR (Engl. Transl.), 1979, 49, 1304 (Chem. Abstr., 1979, 91, 210 789). 4 1 W. E. Jennings, J. H. Hargis. and S. D. Worley, J . Chem. Soc., Chem. Commun., 1980, 30. 27

244

Organophosphorus Chemistrj

1

been estimated by ab initio SCF MO calculations, and protonation at oxygen is predicted, the lone pair of electrons on nitrogen and the P-OH group being syn- or anti-~eriplanar.~~ Other Studies. Temperature-dependent studies of 6~ of the phosphazene (16) showed the PN resonance to be more sensitive to temperature changes than the PO resonance.43Proton n.m.r. studies of hydrogen bonding of phosphine oxides with imidazole were used to calculate thermodynamic p a r a r n e t e r ~ . ~ ~ CH,But

I

0

II

(RO),P=NP(OR),

Ph9pLY

HlC'H /

I

Bu'

(17)

Configuration.-The non-equivalence of geminal nuclei in certain prochiral molecules can also vary with temperature, and in some molecules the nonequivalence disappears on raising the t e m p e r a t ~ r eIn . ~ the ~ case of the neopentyl compounds (17) this phenomenon led to an erroneous claim for restricted rotat i ~ n .46~The ~ . temperature and solvent dependence of diastereotopic nuclei in chiral and prochiral compounds is well established; 47 even so, the non-equivalence usually observed has been useful for the detection of diastereomeric properties,48$ 4 8 for checking optical and as proof of absolute c ~ n f i g u r a t i o n . ~ ~ Spin-Spin Coupling.-A method of suppressing homonuclear and heteronuclear coupling by homonuclear two-dimensional J spectroscopy has been described.62 It involves the measurement of a series of time-domain FID signals as a function of two time variables that are then double-Fourier-transformed to give a twodimensional J spectrum, represented as a function of two frequency variables 42

43 44

45 48

47

4R

19

50 51

52

T . A. Modro, W. G . Liauw, M . R . Peterson, and I . G . Csitmadia, J . Chem. Soc., Perkin Trans. 2, 1979, 1432. L. Riesel, J . Steinbach, and B. Thomas, 2. Anorg. Allg. Chem., 1979, 451. 5 . S-M. Wang, L-Y. Lee, and J-T. Chen, Spectrorhim. Acta, Part A , 1979, 35, 765. J . Jacobus, J . Org. Chem., 1979, 44, 3717. G . Singh and G . S. Reddy, J . Org. Chem., 1979,44, 1057. T. P. Zeleneva, S. I . Parlina, L. K. Vasyanina, and E. E. Nifant'ev, J . Gen. Chem. USSR (Engl. Transl.), 1979,49,484 (Chem. Absrr., 1979,91, 20 612); M . Mikolajczyk, J . Omelanczuk, and J . Drabowicz, Pol. J . Chem., 1979, 53, 317 (Chem. Abstr., 1979, 91, 90714). M. I . Kabachnik, L. S. Zakharov, E. I. Goryunov, and V. A. Svoren, Dokl. Akad. Nauk SSSR, 1979,245, 125 (Chem.Abstr., 1979,91, 38 789); D. A. Predvoditelev, M. K . Grachev, M. V. Galakhov, and E. E. Nifant'ev, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 248 (Chem. Abstr., 1979, 91, 141 116); Z . Biran and J . M. E. Goldschmidt, J . Chem. SOC., Dalton Trans., 1979, 1017; S . Musierowicz, W . T. Waszkuc, and H. W. Krawczyk, Phosphorus Suljiur, 1979, 5 , 377. V. A. Shokol, B. N . Kozhushko, Yu. A . Paliichuk, and Yu. P. Egorov, J . Gen. Chem. U S S R (EngI. Transl.), 1979, 49, 1287. W . Kuchen and J . Kutter, Z . Naturforsch., Teil. B, 1979, 34, 1332; A. Barabas, V. Muresan, and L. Almasi, Org. M a p . Reson.. 1979, 12. 313. K . Lesiak and Z . J . Lesnikowski, Pol. J . Chrm., 1979. 53, 2041 (Cheni. Abstr., 1980, 92, 129 245). L. D . Hall and S. Sukumar. J . Am. Chem. Soc., 1979, 101, 3120.

24 5

Physical Methods

orthogonal to each other. Distinction between homonuclear and heteronuclear coupling is achieved by display projections onto two different axes. JPPand JPM. Geminal PIVCPIT1couplings of up to 150 Hz have been observed in molecules of the type (18), which contrasts with the more normal coupling of 21-30 Hz in the PII1CPII1 rn01ecules.~~ The P1I10CPv coupling constants in the dioxadiphosphorinans (19) vary from 30-34 Hz to 15-1 8 Hz between the isomeric The diphosphine disulphide (20) possesses a long-range coupling 4 J ~of~ 5~H' z . Comparison ~~ of bond lengths in Me,PSe with 'JPs~ shows the direct coupling to be highly anisotropic ( J 11 - J I z - 680 H z ) . ~ The ~ considerably lower magnitude of JPSeR has been used diagnostically. 370, 57

J I ~and F JPN.A nearly linear relationship between 'JPPand 8~ has been reported for the phosphoranes (21).58There have been further studies of lJ1>15~, and reports have appeared on phosphor amid ate^,^^ azides (22),60 and phosphazenes.6I In the cyclic phosphorothioates (23), 1 J ~ iwas 5 ~ 37.5 Hz when the anilide group was axial, but 49.0 Hz when it was equatorial.62 Jpc. In a series of (a-hydroxycycloalky1)phosphonates(24), ~ J P becomes C less positive as the degree of steric congestion about the P-C bond increases.63This L:oupling is also sensitive to the axial or equatorial orientation of the phosphorus grouping in the glycosylphosphonates (25), and in all cases 'JCP-eq > I J C P - ~ ~ . ~ EtOP*$\

Y

Ph,P=CHPPh,

(18)

i R

P-OEt

S

Ph2P+!ph

I1

R

Ch

(20)

(19) NHPh

X H. H. Karsch, Z . Nuturforsch., Teil. B. 1979. 34, 1171; R . Appel and V . Barth, Angrw. Cham., Int. Ed. Engl., 1979. 18, 469.

E. E. Nifant'ev, G. Ya. Legin. S. F. Sorokina, and A. A. Borisenko, J . G m . Chem. U S S R (Eng/. % ? n s / . ) 1979, , 49, 2331 (Cham. Abstr., 1980, 92, 1 1 1 112). x B. Divisia, Tetrahedron, 1979, 35, 181. 5 6 A . Cogne, A. Grand. J . Laugier, J . B. Robert, and L . Wiesenfe1d.J. Am. Chem. SOC.,1980, 102, 2238. 5 7 M. Michalska, I . Orlich-Krezel, and J . Michalski, Tetrahedron, 1978, 34, 2821. 58 H. B. Stegmann, H . V. Dumm, and K. Scheffler, Phosphorus Su(jirr, 1978,5, 159. 5 9 G . A. Gray, G. W. Buchanan, and F. G. Morin, J . Org. Chem., 1979, 44, 1768. 60 J . Mueller and H. F. Schroeder, Z . Anorg. Allg. Chem., 1979, 450, 149. 6 1 B. Thomas, G . Seifert, G . Grossmann, and D. Scheller, Z . Phvs. Chem. (Leipzig), 1979, 260, 225. J. Baraniak, R . W. Kinas, K. Lesiak, and W. J . Stec, J . Chem. SOC.,Chem. Commun., 1979, 940. G . W . Buchanan and F. G . Morin, Cun. J . Chem., 1977, 55, 2885. G . Adiwidjaja, B. Meyer, H . Paulsen, and J. Thiem, Tetrahedron, 1979, 35, 373.

51

'12

(19

9

246


The sensitivity of ~ J P to C substitution at phosphorus and the possible sign of the coupling in trifluoromethylphosphines and their oxides have also been disThe phosphonate ion (26) exhibited a large ~ J P(220 C Hz) compared to its conjugate acid (123 Hz). This evidence, combined with an increase in l J C H and a change in sign of 2 J ~indicates ~ ~ , that the a-carbon atom is planar.66The geminal PIIT coupling is quite sensitive to the orientation of the lone pair of electrons both to aryl carbon atoms, as in (27),67and to aliphatic carbon, e.g. (28).6*In the latter case, the lower couplings were assigned to the configuration with the lone pair on phosphorus and the C-C* bond in a periplanar arrangement. The P-N-C couplings of triazaphosphadiborines are also stereodependent,69and in the amidines (29) it was zero for the syn isomer shown, but 5-10 Hz for the anti form.7oThe P-C couplings for the tin heterocycle (30) and its selenide have also been studied.71Although vicinal PV-C couplings can be rather small in magnitude, in the case of P1I1compounds they are dependent on the orientation of the lone pairs of electrons on and in some instances the coupling can be quite JPH.The phospha-alkene (31) is interesting in that the P-H bond must have considerable s character ; nevertheless the direct P-H coupling constant is only 166.6 H z . This ~ ~ is about 40 Hz less than the couplings observed in (trifluoromethy1)phosphines. There have been some further studies of protonated cyclic pho~phites,'~ and * J ~ of H chiral bicyclic phosphoranes has been found to be related to onf figuration.^^ J P C ~ HThe . influence of orbital configuration and the charge on phosphorus upon P-H and P-C-H coupling constants has been examined through MOLCAO c a l c ~ l a t i o n s .Further ~~ examples of the use of JPCHto determine the configuration 78 and conformation 7 9 of phosphoryl compounds have been reported. Thus JPCHis 16 Hz for the phosphorinan (32) but zero for its isomer in which the phosphoryl oxygen is The relationship between the P-C-C-H coupling constants and dihedral angle has been investigated for phosphonium 65 66

67 68 69

70 71

72

73 74

75 76 77 76 79

P. Dagnac, J . L. Virlichie, and G . Jugie. J . Chem. Soc., Da/ton Trans., 1979, 155. T. Bottin-Strzalko, J . Corset, F. Froment, M . J . Pouet, J . Seyden-Penne, and M . P. Simonnin, J . Org. Chem.. 1980, 45, 1270. V. V. Negrebetskii. Zh. Strukt. Khim., 1979, 20, 540 (Chem. Abstr., 1979, 91, 174 361). S. D. Venkatararnu, K . D. Berlin, S. E. Ealick, J. R. Baker, S. Nichols, and D. van der Helm, Phosphorus Sulfur, 1979, 7 , 133. K. Barlos. H . Noeth, B . Wrackmeyer, and W. McFarlane, J . Chem. Soc., Dalton Trans., 1979, 801. V. V. Negrebetskii, L. Ya. Bogel'fer, A . F. Grapov, V. N . Zontova, and N . N . Mel'nikov, J . Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 61 (Chem. Abstr., 1979, 90, 186 260). H . 0. Berger, H . Noeth, and B. Wrackmeyer, Chem. Ber., 1979, 112, 2866. E. E. Nifant'ev, L. T. Elepina, A. A. Borisenko, M . P. Koroteev, L. A. Aslanov, B. M . lonov, and S . S. Sotman, Phosphorus Sulfur, 1979, 5 , 315; S. Samaan, ibid. 1979, 7, 89. 0. J . Scherer and M . Puettmann, Angew. Chem., I n t . Ed. Engl., 1979, 18, 679. H . Eshtiagh-Hosseini, H . W . Kroto, J . F. Nixon, S. Brownstein, J. R . Morgan, and K . F . Preston, J . Chem. Soc., Chem. Commun., 1979, 653. R. Weiss, L. J . Vande Griend, and J . G. Verkade, J . Org. Chem., 1979, 44, 1860. C . Bonningue, J . F. Brazier, D. Houalla, and F. H . Osman, Phosphorus SulJirr, 1979,5, 29 I . L. I . Vinogradov, Fosfororg. Soedin. Polini., 1978, 4, 35 (Chem. Abstr., 1980, 92, 93 542). B. A. Arbuzov, 0. A . Erastov, S. Sh. Khetagurova, T. A . Zyablikova, R . A . Kadyrov, and V. N . Smirnov, Bull. Acad. Sci. USSR, Dic. Cheni. Sci., 1979, 28, 2061. 0. A . Raevskii, N . G. Mumzhieva, M . M. Gilyazov, and A. A. Karelov, Bull. Acad. Sci. USSR, Div. Chem. Sci., 1979, 28, 2073 (Chem. Abstr., 1980, 92, 128 270).

Physical Methods

247

0

8

(EtO),PCHCO,Me (24)

Me

(25)

(26) Ch

R MeS

Me,N

II

\ /

C=N

/

PR,

-.

Ph Ph

Z

F,C=PH

(31)

betainesBoand spirotetraoxyphosphoranes.*lThe P-N-C-H coupling constant was an important parameter in the conformational analysis of the hydrazine heterocycles (33).82The large value (24-25 Hz) of JITCHfor the phosphorodiamide (34) was attributed to the dihedral angle of nearly 03.83 Separate linear correlations of JPNCH with 6(CH,) have been observed in a series of trisaminophosphine derivatives (35), depending on whether the group Y could interact by n-donation or The use of JPOCH in the conformational analysis of the dioxaphosphorinans (36; X = 0) was assisted by utilization of the rigid transdecalin An example of the problems usually encountered is shown in the n.m.r. study of 1,3,6,2-trioxapho~phocans.~~ A study of the 1,3,5-dioxaphosphorinans (37) showed that 4 J p ~is~also ~ :stereo-de~endent.~' ~ A long-range coupling (5JPH = 2 Hz) has been recorded for the phosphinimine (38).88 Relaxation and N.Q.R. Studies.-The problem of suppressing lineshape artifacts arising from radiofrequency inhomogeneity and other pulse imperfections has HI)

H1

HZ 83 84

85 87

P. J. Butterfield and J. C. Tebby, J . Chem. SOC.,Perkin Trans. I , 1979, 1189.

M . Willson, J . Navech, and R. Burgada, Phosphorus Sulfur, 1979, 6 , 457. H . J. Merrem, R. Ehehalt, and U . Engelhardt, Client. Ber., 1979, 112, 3589; H . J . Merreni, U. Engelhardt, and H . Bauer, ibid., p. 1482. T. S . Cameron, R . E. Cordes, T. Demir, and R . A . Shaw, J. Chem. SOC.,Perkin Trans. I , 1979, 2896. R . D. Kroshefzky and J . G . Verkade, Phosphorus Sulfur, 1979, 6 , 391. D. G . Gorenstein and R . Rowell, J . Am. Chem. SOC.,1979, 101, 4925. J . P. Dutasta, J . B. Robert, and M . Vinceus, Tetrahedron Lett., 1979, 933. K. K . Valetdinov, A. N . Zuikova, N. Sh. Yakiminskaya, T. A . Zyablikova, E. N . Ofitserov, and A . V. Il'yasov, J . Gen. Client. U S S R (Engl. Tronsl.), 1978,48, 2406 (Chem. Ahstr., 1979, 90, 152 298). H . Yoshida, T . Ogata, and S. Inokawa, Bull. Chem. So(..Jpn., 1979, 52. 1541.

24 8

Organophosphorus Chemistry 0

I

t / \

S

OPh

14A

HB

MeN

been Some 31Prelaxation studies have been reported for cyclic thiophosphoryl corn pound^,^^ for pyridylphosphonate~,~~ and for diethyl hexylpho~phonate.~~ Chlorine-35 n.q.r. spectroscopy has been used to study the mobility of trichloromethyl groups in phosphazenes 9 3 and to investigate the ionic character of chloro(trifluoromethy1)phosphines and their Also, the spectra of a number of chlorophosphoranes 94 and cyclic phosphadiazines 95 have been correlated with their structures. 2 Electron Spin Resonance Spectroscopy Although there has been a theoretical study of the geometries and e.s.r. coupling constants of dico-ordinate phosphorus radicals such as H2P,96most of the reports concern PIr1 and PIv radical^.^' The radicals (39) that are produced upon radical addition to vinylphosphanes exhibit quite large couplings to phosphorus [a(P) = 63-1 10 GI, in accordance with appreciable delocalization of the unpaired electron at phosphorus. An appreciable contribution by resonance from (39b) was not anticipated from previous studies of a-phosphinoalkyl radicals. Similar radical additions to vinylphosphonates give a-phosphorylalkyl radicals with a(P)= 4 1 4 2 G.9sPhosphoranyl radicals (40) are formed at I70 K by addition of the t-butoxyl radical to isocyanatophosphanes, but above this temperature an isomer is formed with a(P)= - 7.3 G and a('")= 129.4 G, 89

90 91

92

93 9.1

A. J. Vega, A . D. English, and W. Mahler, J. Magn. Reson., 1980. 37, 107. J. Tabony, Spectrochim. A d a , Part A , 1979, 35, 217. D. Redmore, Phosphorus Sulfitr, 1979, 5 , 271. G . Klose, T. Goetze, and G. Grossmann, Chem. Ahstr., 1980, 92, 145 968. I. A. Kyuntsel, V. A . Mokeeva, G . B. Soifer, and 1. G. Shaposhnikov, J . Magn. Reson.,

1978, 32, 403. E. S. Kozlov, N. P. Kolesnik, L. G . Dubenko. and M. I . Povalotskii, J. Gen. Chem. U S S R S. V. Fridland, A . I . Efremov, and B. D. Chernokal'skii, ihid., p . 873 (Chem. Abstr., 1979, 91, 73 815). E. A. Romanenko. Yad. Kuadrupol'nyi Re:on., 1976. 1, 120 (Chem. Ahstr., 1979, 91, 73 824). A. Hinchcliffe and D. Ci. Bounds, J . Mol. Struct., 1979, 54, 231. W. B. Gara and B. P. Roberts, J. Chem. Soc., Perkin Trans. 2, 1978, 150. J . A . Baban, C . J. Cooksey, and B. P. Roberts, J. Chem. Soc., Perkin Trans. 2, 1979, 781. J . A . Baban and B. P. Roberts, J. Chem. Soc., Chem. Commun., 1979, 373.

(Engl. Transl.), 1979, 49, 666 (Chem. Abstr., 1979, 91, 39052); 9s

08

97 80

99

Physical Methods

249

indicating a transformation into the phosphonium ylide structure (41).'0° It has also been reported that the two phosphoranyl geometries (42) and (43), which have coupling constants a(P) = 885.6 and 909.2 G can be observed at low temperatures. * 0 1 The decrease in a(P) with lowering of temperature for some o-phenylene radicals has been assigned to a change in the population of two t.b.p. phosphoranyl radicals (44)and (45).lo2

P

0-P

O

0

q

I

'OBu' NCO

I (TMS),N -

I '

OTMS (43)

n/

Bu'O

ButO (44)

(45)

Also of interest is the increase in coupling constants of phosphorus to the radical anion of trimethyl phosphite upon raising the temperature from 77 to 126 K ; this increase has been assigned to a change in the orientation of the lone pair of electrons from apical to radial, i.e. (46) to (47).lo3The e.s.r. parameters of Ph,PBr correspond to a structure between C,, (cf. F,P) and C,, (cf. Ph,PCI). lo4 Thee.s.r. spectraofseveral a-phosphoryl radicals(48) have beendescribed,lo5*l o 6 and the P-C rotation barrier (15.1 kJ mol-l) has been calculated for the methylenephosphonic acid radical (48; R = Y = . ) . I o e Hydrogen abstraction from iminophosphoranes gives n-radicals with spectra that are typical of a-aminoalkyl radicals, indicating that (49) is the main contributing structure. The magnitude of 1 1 ) ~

1'11

1'12

109 104 10'1

106

J . A. Baban and B. P. Roberts, J . Chem. SOC.,Chem. Commun., 1979, 537. B. P. Roberts and K . Singh, J . Chem. Soc., Chem. Commun., 1979, 980. 9. 1,. Tumanskii, A. A. Khodak, S. P. Solodovnikov, N . N . Bubnov, V. A . Gilyarov, and M . 1. Kabachnik, Bull. Acad. Sci. USSR(Eng1. Trans/.).1979,28, 1520(Chem. Abstr., 1979, 91, 174 470). R . L. Hudson and F. Williams, J . Chem. Soc., Chrnt. Commun., 1979, 1125. T. Berclaz, M. Geoffrey, L. Ginet, and E. A. C. Lucken, Chem. Phys. Leu., 1979,62, 515. V. Cerri, M. Boyer, and P. Tordo, Tetrahedron Lett., 1979, 1437; M. S. Skorobogatova, A . Sh. Mukhtarov, Ya. A. Levin, and A. V. Il'yasov, Bull. Acad. Sci. USSR, Div. Chem. Sci., 1979, 28, 1731 (Chem. Absrr., 1980, 92, 6611). M. Geoffroy, L. Ginet, and E. A. C. Lucken, Mol. Phys., 1979,37, 1649.

250


II

(RO),P-eY,

a(P)increases rapidly with rise in temperature, and hence the coupling is probably positive.lo7 Phosphorus coupling in the radicals (50) suggested that the radical may be in equilibrium with a five-co-ordinate species.'OBAnother study indicated the presence of Pv-Pvr tautomerism of a radical with non-equivalent ligands. O!' There have also been several reports on nitroxyl radicals such as ( 5 1 ) . 1 1 0

3 Vibrational and Rotational Spectroscopy Band Assignments.-The infrared and Raman spectra of difluorophosphine ('H and 2H) have been analysed and the thermodynamic parameters calculated. The spectra of the trifluoromethylphosphine chalcogenides ( 5 2 ; Ch = S or Se) have been assigned.' * Assignments of the spectra of trialkylphosphine-carbon disulphide adducts indicate that there are extensive mechanical couplings in the molecules.113 The differences in the i.r. spectra of diastereoisomeric nucleoside phosphonates have been studied. R. S . Hay, B. P. Roberts, K. Singh, and J. P. T. Wilkinson J. Chem. Soc., Perkin Trans. 2, 1979, 756. l o 8 H. B. Stegmann, H. Mueller, K. B. Ulmschneider, and K. Schemer, Chem. Eer., 1979,112, 2444. l o g A. I. Prokof'ev, T . I. Prokof'eva, 1. S. Belostotskaya, N. N. Bubnov, S. P. Solodovnikov, and V. V. Ershov, Dokl. Akad. Nauk SSSR, 1979, 246, 340 (Chem. Absrr.. 1979, 91, 174 319). 1 l 0 A . A. Barlev, A. Sh. Mukhtarov, A . V. Il'yasov, Ya. A. Levin, and M. S. Skorobogatova, Bull. Acad. Sci. USSR, Dic.. Chem. Sci., 1979,28,217 (Chem.Abstr., 1979,90, 1 36 926) ;A. A. Barlev, B. M. Odintsov, A . V. Il'yasov, A. Mukhtarov, and F. F. Gubaidallin, Zh. Fiz. Khim., 1979, 53, 1375 (Chem. Abstr., 1979, 91, 156 870); M. P. Sokolov, A . A. Barlev. A. Sh. Mukhtarov, T . A. Tarzivolova, B. G. Liorber, A . V. Il'yasov, and A. I . Razumov, J. Gen. Chem. USSR (Engl. Transl.), 1979, 49, 1086. J. R. Durig, A. J. Zozulin, J. D. Odom, and B. J. Streusand, J . Raman Spectrosc., 1979, 8, 259; V. D. Dunning and R. C. Taylor, Spectrochim. Acta, Part A, 1979, 35, 479. 1 1 2 P. Dehnert, R. Demuth, and J. Grobe, Spectrochim. Acta, Part A, 1980, 36, 3. 1 1 3 I . S. Butler, and J. Svedman, Spectrochim. Acra, Part A, 1979, 35, 425. 114 0. M. Nesterova, B. S. Kikot, and M. N. Preobrazhenskaya, Khim. Getorotsikl. Soediri., 1979, 181 (Chem. Abstr., 1979, 91, 5433). 107

Physical Methods

25 1

Stereochemistry.-The vibrational spectra of triallylphosphine indicated that the molecules adopt a gauche conformation. l 5 A study of the modes associated with the R2Ngroups of the phosphanes (53) favoured a C,geometry for these groups.IJ6 There are further examples of the use of v(P===O) in the conformational analysis of 1,3,2,-dio~aphosphorinans,*~~ l7 and its application to the study of conformations of oxazaphospholidines has been discussed. IR

Bonding.-Trimethylphosphine chalcogenides and their perdeuteriated analogues have been studied, and the P=Ch stretching force-constants were derived.llg A Raman spectral study of arylphosphonyl and arylthiophosphonyl compounds was used to compare the interactions of the aryl rings with various phosphorus groupings. 120 The strong interest in hydrogen bonding involving phosphoryl groups, as shown in (54), continues. These studies include the influence of a substituted vinyl group at phosphorus on the electron-donor capabilities of the phosphoryl group,lZ1correlations of v(P-0) with heats of complexation,122intramolecular hydrogen bonding, 2 9 steric effects involving halogenoacetic acids,124 isotopic hydrogen exchange in dialkylphosphine-alcohol-amine systems,125 and the influence of the solvent on the extracting power of triethylphosphine oxide.126 The stability constants of some metal chelates of P-styrylphosphonic acid have also been determined."' A large degree of delocalization of the lone pairs of nitrogen towards the phosphorus atom in spiropentaco-ordinate phosphoranes (55) was indicated from a study of V ( N H ) . ~ ~ ~ G . Davidson and S. Phillips, Spectrochim. Acta, Part A , 1979, 35, 83. G . Davidson and S. Phillips, Specrrochim. Acta, Purr A , 1979, 35, 141. R. P. Arshinova, T. D. Sorokina, A . B. Rernizov, G . E. Koroleva, and B. A . Arbuzov. Bull. Acad. Sci. USSR, Dic. Chem. Sci., 1979, 28, 2065 (Chem. Abstr., 1980, 92, 128 269). 11s I. E. Boldeskul, G . A . Kalyagin, and Yu. V. Balitskii, Zh. Prikl. Spekrrosk., 1979,31, 109, (Chem. Abstr., 1979, 91, 131 479). 119 F. Watari, E. Takayama, and K . Aida, J . Mol. Struct., 1979, 55, 169. 1 2 0 V. V. Dorokhova, G . V. Ratovskii, and V. I. Dmitriev, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 6 8 . 1 2 1 I. P. Lipatova, V. V. Moskva, T. Sh. Sitdikova, E. I. Antropova, and S. A. Sarnartseva, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 72. 1 2 2 V. E. Bel'skii and L. K h . Ashrafullina, J . Gen. Chem. U S S R (Engf.Transl.), 1979, 49, 1968. 123 E. P. Trutneva, R . R . Shagidullin, L. V. Stepashkina, and R. I . Rizpolozhenskii, Bull. Acad. Sci USSR,Diu. Chem. Sci., 1978,27, 2433 (Chem. Absrr., 1979,90, 120 814). 12.1 M. Grundwald and M . Szafran, Pol. J . Chem., 1979. 53, 829. 125 E. V. Ryl'tsev, A. K . Shurubura, V. Ya. Sernenii, and Yu. P. Egorov, Spekrrosk. Mol. Krist., Kieu, 1978, 156 (Chem. Abstr., 1979, 91, 19 390). 126 E. V. Ryl'tsev, I. F. Tsymbal, V. Ya. Semenii, and Yu. P. Egorov, J . Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 898. 1 2 7 E. N. Rizkalla and M. T. M. Zaki, Talanfa, 1979, 26, 979. 1 2 8 R . Mathis, T. Bouissou, M . Bon, A . Schmidpeter, J . Luber, and M. Volz, Specrrochim. Acta, Part A , 1979, 35, 745.

115

116 11'

252


Microwave Spectra.-The microwave spectra of MeC--P and its deuteriated analogues have been analysed, and its dipole moment was estimated to be 1.499 D.lZ9Although a dipole moment could not be obtained for MeH,SiPH ", the microwave data indicated that the molecule has a short Si-P bond.I3O A study of P:j5C1, has also been reported.'"'

4 Electronic Spectroscopy

Absorption Spectroscopy.-Further studies on the spectra of arylphosphines (56) have been pub1i~hed.I~~ Five individual bands can be envisaged in the U.V. spectrum of diethylphenylphosphine, and the incorporation of the frequencies of these bands into molecules-in-molecules (MIM) calculations which take into account the possibility of donor and acceptor properties by the diethylphossphino-group indicates that both pn-pn conjugation and an interaction of the n-orbitals of the ring with the vacant orbitals of phosphorus are present.':'" The bathochromic shifts observed in the spectra of arylphosphines as the bulk of the aryl group is increased (using orrho-effects) have been attributed to a re-adjustment of the orbital energies with a change in bond angle rather than a change in conjugation.'"4 It has been found that the diphenylphosphino-group (Ph,P) only weakly interacts with the n-system in the triarylcarbenium ion (57).136 The U.V. spectra of the thiophosphites ( 5 8 ) have been studied with the aid of quantumchemical calculations.136U.V. spectroscopy was used to support studies of the interaction of aryl rings with dihalogenophosphoryl groups using vibrational spectroscopy. * 2 o Work o n cis-4-diphenylphosphinylstilbenes13' and some dye intermediates 13* has also been reported. In an investigation of PCI, in polar solvents it was found that, whilst the PC1,anion absorbed at 270 and 345 nm, the PCI, ions showed no absorption in this ~ e g i 0 n . The l ~ ~presence of a phenyl group inevitably produces an absorption for the cations (59),and p,-d,, conjugation is believed to be an important factor.140 H . W . Kroto, J . F. Nixon, and B. P. C. Simmons, J . Mol. Spectrosr., 1979, 77, 270. J. R. Durig, M . Jalilian, Y . S. Li, and R. 0. Carter, J . Mol. Sfrucr., 1979, 55, 177. 131 J . G . Smith, J . Mol. Spectrosc., 1979, 7 7 , 169. 132 G. V. Ratovskii, A . M. Panov, Yu. 1. Sukhorukov, 0. E. Yakutina, and E. N . Tsvetkov, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 479. lSs F. Kh. Chibirova, V. M. Ryaboi, I . P. Romm, Z. M. Boskakova, and E. N . Gur'yanova, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 1711 . 1 3 4 A. I . Bokanov and B. 1. Stepanov, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 1036. 135 A. 1. Bokanov, N. N. Bychkov, V. V. Negrebetskii, and B. I. Stepanov, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 860. 13* A. V. Chernova, M. B. Zuev, R. R. Shagidullin, G. M . Doroshkina, I . A. Nuretdinov. and E. V. Bayandina, Zh. Obshch. Khim., 1979, 49. 2002 (Chem. Absrr., 1980, 92, 3 1 294). Is7 L. Alder, D . Gloyna, H . G. Henning, M . V. Koz'menko, and M . G. Kuz'min, Vestn. Mosk. Unit'., Ser. 2, Khim., 1979, 20, 248 (Chem. Ahstr., 1979, 91, 123 188). 138 V. V. Korrnachev, G. P. Pavlov, V . A . Kukhtin, and R . S. Tsekhanskii, J . Gen. C'hem. USSR (Engl. Transl.), 1979, 49, 2189 (Chrm. Abstr., 1980, 92, 1 1 1 1 10). 139 L. M . Sergienko, G. V. Ratovskii, A . M . Dodonov, and A . V. Kalabina, J . Grn. Chem. U S S R (Engl. Transl.), 1979, 49, 1743. 140 L. M . Sergienko, G . V. Ratovskii, V. 1. Dmitriev, and B. V. Tikokhin,J. Gen. Chem. U S S R (EnRI. Transl.), 1979, 49, 275. 129

130

Physical Methods

253 P

QPR2

Y (56)

h

2

P

-

e

6(C,H,NMeJ,

( 5 7)

+

(RS),P

Ph, PC1, - I ,

(58)

(59)

A number of radical reactions involving organophosphorus compounds have also

been studied.I4l Photoelectron Spectroscopy.-The formation of phosphapropyne, MeC--P, was confirmed by p.e. The low basicity of A3-phosphorin (phosphabenzene) has been attributed to its inability to undergo geometric rearrangement upon p r ~ t o n a t i o n . ’The ~ ~ gas-phase proton affinities of cyclic phosphites have been studied, and an axially orientated lone pair of electrons on phosphorus was estimated to be more basic than an equatorially orientated lone pair.144There has been a detailed p.e. study of the electronic structure and reactivity of a range of iminophosphoranes (60). CND0/2 calculations indicated that delocalization of the positive charge on to the phenyl rings of (60; R1=Ph) lowers the first ionization energy. 145 There have been several studies of phosphoryl comp o u n d ~ , ’14’ ~ ~and ’ additive substituent increments have been derived to enable p n , 0 ionization potentials to be c a l c ~ I a t e d . *The ~ ~ very high vafue of the C-C n-ionization potential ( 1 1.5 lev) for (61 ; Y = vinyl, Z = CI) has been attributed to the very powerful inductive effect of the P(O)Cl, Replacement of chlorine by methoxyl in this molecule increases the charges on the phosphoryl oxygen and on C=C, and decreases the charge on p h o s p h o r u ~The . ~ ~PIrl-Pv ~ tautomeric equilibrium for the phosphoranes (62) has also been studied by p.e. spectroscopy. I 5 O 0

R’,P=NR’ (60)

II

Y PZ: (61)

H. Horii, S. Fujita, T. Mori, and S. Taniguchi, Bull. Chem. SOC.Jpn., 1979, 52, 3099; R. 1. Zhdanov, N. A. Buina, N. G. Kapitanova, and 1. A . Nuretdinov, Synthesis, 1979,269; D. Griller, K. U. lngold and L. K. Patterson, J. Am. Chem. SOC., 1979, 101, 3780. li2 N. P. C . Westwood, H . W. Kroto, J . F. Nixon, and N . P. C. Simmons, J. Chem. SOC., Dalton Trans., 1979, 1405. l A 3 A . J . Ashe, M.K. Bahl, K. D. Bomben, J . K. Gimzewski, P. G. Sitton, a n d T . D. Thomas, J . Am. Chem. SOC., 1979, 101, 1764. R . V. Hodges, F. A. Houle, J. L. Beauchamp, R . A . Montag, and J. G. Verkade, J. Am. Chem. SOC.,1980, 102, 932. 1 4 5 K. A. 0. Starzewski and H. tom Dieck, Inorg. Chem., 1979, 18, 3307. 1 4 6 V. V. Zverev, Ya. Ya. Villem, V. E. Bel’skii, and Yu. P. Kitaev, Chem. Abstr., 1980,92, 119 203. 1 4 7 V. V. Zverev, J. Villem, V. E. Bel’skii, and Yu. P. Kitaev, Bull. Acad. Sci. USSR, Ditt. Chem. Sci., 1979, 28, 74 (Chem. Abstr., 1979, 90, 167 817). 1 4 8 V. V. Zverev, J. Villem, R . G . Islamov, and Yu. P. Kitaev, J . Gen. Chem. USSR (Engl. Transl.), 1979, 49, 1522 (Chem. Abstr., 1980, 92, 5726). 149 V. V. Zverev, Ya. Ya. Villem. L. V. Ermolaeva, and A . F. Lisin, Dokl. Akad. Nauk SSSR. 1979, 246, 1368 (Chem. Abstr., 1979, 91, 131 722). 150 D. Houalla, M. Sanchez, D. Gonbeau, and G. Pfister-Guillouzo, Nouo. J . Chim.. 1979, 3, 507 (Chem. Abstr., 1980, 92, 21 889). 141

9*

2 54

Organophosphorus Chemistrj,

5 Diffraction X-Ray.-The flood of publications in this area continues, and over 80 structures have been determined over the past twelve months. The reports on PI1compounds concern pho~pholes,'~'a z a p h o ~ p h o l e s153 , ~ ~and ~ ~ two silyl derivatives (63).15:$ The studies of P1IXcompounds have involved three p h o s p h i n e ~ , ' two ~ ~ silyl a c y c l ~ d i p h o s p h a z a n eand ,~~~ the diazabicyclo-compound (64). Is7 The dithiaphosphorinan (65) was found to adopt the chair conformation shown, but its cis- and trans-oxides, e.g. (66), prefer a twist c o n f ~ r m a t i o n . ' Other ~~ studies have shown that the spirobiphosphite (67) has axial methoxy-groups,159 and a comparison of the structures of the ribopyranoside phosphite (68) with its phosphate showed that the chair conformation is retained.160 The bulk of the X-ray diffraction data concerns PIv compounds. Salts examined include tetraphenyl,lgl tetra-alkyl, 162 and phosphetanium 163 derivatives, whilst ylides of the carbodiphosphorane,164carbotripho~phorane,'~~ and keto-stabilized type have also been studied. The structures of iminophosphoranes that are

PMe PhN-N

Y \N/p\N/Y

I

SiR,

Ph

R

(63) 1.51

G. De Lauzon, €3. Deschamps, J . Fischer, F. Mathey, and A. Mitsch1er.J. Am. Chem. Sot,.,

I52

J. H. Weinmaier, J . Luber, A. Schmidpeter, and S. Pohl, Angew,. Chem., I n l . Ed. EngI.,

1980, 102, 994.

153

154

155

158

1979, 18, 412. S . Pohl, Chem. Ber., 1979, 112, 3159.

E. P. Kyba, A. M. John, S. B. Brown, C. W . Hudson, M. J. McPhaul, A. Harding, K . Larsen, S. Niedzwiecki, and R. E. Davis, J. Am. Chem. SOC.,1980,102, 139; H. H. Karsch,

U. Schubert, and D. Neugebauer, Angcw. Chcm., Int. Ed. End., 1979,18,484; 0. Dahl and S. Larsen, J. Chcm. Res. CS), 1979, 396; A. W. Cordes. P. F. Schubert, and R . T. Oakley, Can. J. Chem., 1979, 57, 174. A. W. Cordes, P. F. Schubert, and R . T. Oakley, Can. J. Chem., 1979, 57, 174; G. Becker and 0. Mundt, Z. Anorg. Allg. Chem., 1979, 459, 87. M. L. Thompson, R. C. Haltiwanger, and A . D. Norman, J. Chem. SOC..Chem. Commun., 1979, 647.

B. A. Arbuzov, V. D. Cherepinskii-Malov, E. N. Dianova, A. I. Gusev, and V. A. Sharapov, Dokl. Akad. Nauk SSSR, 1979, 247. 1150 (Chem. Abstr., 1980,92, 21 710). 158 R. 0. Hutchings, B. E. Maryanoff, M. J . Castillo, K. D. Hargrave, and A. T. McPhail, J . Am. Chem. SOC., 1979, 101, 1600. 158 L. E. Carpenter, R. A. Jacobsen, and J. G. Verkade, Phosphorus Sulfur, 1979, 6, 475. l R 0 A. C . Bellaart, D. Van Aken, H. M. Buck, C . H. Stam, and A. Van Herk, Recl. Trail. Chim. Pays-Bas, 1979, 98, 523. 1 6 1 U. Mueller, 2. Naturforsch., Teil. B , 1979, 34, 1064. 162 S. F. Solodovnikov, T. M.Polyanskaya, V. I. Alekseev, Yu. A. Dyadin, and V. V. Bakakin, Dokl. Akad. Nauk SSSR, 1979, 247, 357 (Chem. Ahstr., 1979, 91, 174 708). 183 Mazhar-ul-Haque, Acta Crystallogr., Sect. B, 1979, 35,2601. 184 H. Schmidbaur and G. Hasslberger, Angew Chem., Int. Ed. Engl., 1979, 18, 408. 165 H . H. Karsch and B. Zimmer-Gasser, Angew. Chem., Znf. Ed. Engl., 1979, 18, 484; B. Zimmer-Gasser. D. Neugebauer, U. Schubert, and H. H. Karsch, 2. Naturforsrh., Teil. B, 15'

1979, 34, 1267.

166

M. Yu. Antipin, E. A. Kalinin A. E. Struchkov, I . M. Aladzheva, T. A. Mastryukova, and M. 1. Kabachnik, Zh. Strukr. Khim., 1979, 20, 638 (Chem. Absrr., 1980, 92, 67 975).

Physical Methods

255

S

II

R-P-OAr

I

OMe

(68)

(70)

cyano-stabilized, 167 phosphoryl-stabilized,168 and boron-stabilized 169 have been determined. Sixteen reports on phosphine chalcogenides have appeared. Apart from Me,PSe,56 most are diphenyl compounds,170the remainder being chiral or heterocyclic compounds; 1 7 1 the most unusual structure was the manganonorbornyl compound (69).172 I n the phosphinic acid class, several cyclohexyl I n the compounds have been studied173together with a chiral ester and phosphoric acid class, phenyl (70; R = Ph),175g l y ~ y l m e t h y l glycosyl,64 ,~~~ difchlorophenoxy)methyl,177 and some heterocyclic compounds 178 have received attention. X-Ray diffraction studies of compounds without P - C bonds have M. Yu. Antipin, A. E. Kalinin, Yu. T. Struchkov, and Yu. P. Egorov, Zh. Strukt. Khim., 1979, 20, 868 (Chem. Ahstr., 1980, 92, 164 041). l f i R A. F. Cameron, I. R. Cameron, and R. Keat, Arta Crystallogr., Sect. B, 1979. 35, 1373. 169 H. Schmidbaur, H. J. Fueller, and A. Frank, Chem. Ber., 1979, 112, 1448. I 7 O S. Kulpe and I. Seidel, Krist. Tech., 1979, 14, 1421 (Chcm. Abstr., 1980, 92, 156 212); S. K u b e and I. Seidel, Z. Chcm.. 1979. 19, 302; 0. Orarna, K. Neininen, M. Karhu, and R. Uggla, Cr.vsr. Struct. Commun., 1979, 8, 909; 0. Orama, M. Karhu, R. Uggla, and U. Schubert, ibid., p. 905; 0. Orarna, M . Karhu, M. Nasakkala, M Sundberg, and R. Uggla, ibid., p. 409; D. G. Naae and T-W. Lin, J. Fluorine Chem., 1979, 13, 473; D. Thierbach and F. Huber, Z. Anorg. A&. Chem., 1979, 457, 189. 1 7 1 S. E. Ealick, J. R . Baker, D. Van der Helm, and K. D. Berlin, Acta. Crystallogr., Sect. B, 1970, 35, 1107; Z. Galdecki, M. L. Glowka, and K. M. Pietrusiewicz,J. Chem. Soc., Perkin Truns. 2, 1979, 1720; B. R . Stults and K. Moedritzer, Cryst. Struct. Commun., 1979, 8, 787; Z. Galdecki. Acta Crystallogr.,Sect. B, 1979,35, 2225; M. J. Gallagher, J. Peterson, and A. D. Rae, Cryst. Struct. Commun., 1979, 8, 587; M. J . Gallagher and A. D. Rae, ibid., p. 583. 172 E. Lindner, A. Rau, and S. Hoehne, Angew. Chem., Int. Ed. Engl., 1979, 18, 534. 173 L. A. Aslanov, S. S. Sotman, V. E. Rybakov, L. G. Elepina, and E. E. Nifant’ev, Zh. Strukt. Khim.. 1979, 20, 758 (Chem. Ahstr., 1980, 92, 32 356); V. V. Tkachev, L. 0. Atovmyan, N. A. Kardanov, N. N . Godovikov, and M. I. Kabachnik, ibid., p. 653; N. A. Kardanov, N. N. Godovikov, V. V. Tkachev, L. 0. Atovmyan, and M. 1. Kabachnik, Bull. Acati. Sci. U S S R , Dio. Chem. Sci., 1979, 28, 1507 (Chem. Absrr., 1979,91, 175 448). 1 7 4 V. V. Tkachev, L. 0. Atovmyan, N. A. Kardanov, N. N. Godovikov, and M. 1. Kabachnik, Zh. Strukt. Khim., 1979,20, 553 (Chem. Ahstr.. 1979,91, 166 536); G. Maas and R. Hoge, Acta. Crystallogr., Sect. B, 1980, 36, 499. 179 R. L. Lapp and R. A. Jacobson, Cryst. Struct. Commun., 1980, 9 , 6 5 . 1 7 6 P. Knuuttila and H. Knuuttila, Acta Chem. Scand., Ser. B, 1979, 33, 623. 1 7 7 S. Kulpe and I. Seidel, Krist. Tech., 1979, 14, 1089; Z Chem., 1979, 19,425. 1 i R J. P. Dutasta, A. Grand, A. C. Guirnaraes, and J. B. Robert, Tetrahedron, 1979, 35, 197; W . Zeiss, H . Henjes, and D. Lux, Z. Nuturforsch., Teil. B, 1979, 34, 1334; P. A . Kamrninga and A. Vos, Cryst. Struct. Commun., 1979, 8, 743. IR7

256


mainly concerned phospha~enes,''~phosphates,laOthiophosphates,181 phosphoramidates,182 and various arnino-compound~.~~+ All the Pv compounds studied have been bicyclic. Of the spirobicyclic type,lH' the sulphur derivatives (71) la5 are probably of most interest. The remaining compounds in this class have fused rings, such as (72).lE6 Electron and Neutron Diffraction.-The stereochemistries of the thienyl and chforomethyf dichlorides (73) have been determined by electron diffraction. A

179

180

181

182

183

184

185 186

187 188

Y. S. Babu and H. Manohar, Acta Crysrallogr., Sect. B, 1979, 35, 2363; M . J . Begley. D. B. Sowerby, and T. T. Bamgboye, J. Chem. SOC., Dalton Trans., 1979, 1401; A . Schmidpeter and H. Eilets, Z. Naturforsch., Tril. B, 1979, 34, 911; J. 0. Bovin, J. F. Labarre, and J. Galy, Acra Crysrallogr. Sect. B, 1979, 35. 1182; A. Perales, J. Fayos, J. C. Van de Grampel, and B. De Ruiter, ihid., 1980, 36, 838. S. Yokoyarna, T. Miyazawa, Y. Iitaka, Z. Yamaizumi, H. Kasai, and S. Nishimura, Nucleic Acids, Symp. Ser., 1979, 6, S75 (Cham. Absrr., 1980, 92, 141 960); T. Srikrishnan, S. M. Fridey, and R. Parthasarathy, J. Am. Chem. SOC.,1979, 101, 3739; D. E. Beckman and R. A. Jacobson, J. Agric. Food Chem., 1979,27,712; C . L. Barnes and S. W. Hawkinson, Acra Crystallogr., Sect. B, 1979, 35, 1724; 2. Galdecki, M. L. Glowka, and A . Zwierzak, Phosphorus Sulfur, 1979, 5, 299; J . A. Gerlt, D. F. Chodosh, R. E. Drews, and R. D. Adams, J. Org. Chem., 1980,45, 1282. L. Kutschabsky, A. Messerschmidt, and H. Sohr, Tetrahedron, 1979, 35, 499; A . E. Kalinin, V. G. Andrianov, and Yu. T. Struchkov, Bull. Acad. Sci. U S S R , D ; P .Chem. Sci., 1979, 28, 727 (Chem. Abstr., 1979, 91. 38 861). V. L. Boyd, G. Zon, V. L. Hirnes, J. K. Stalick, A. D. Mighell, and H. V. Secor, J. Med. Chem., 1980, 23, 372; J. Karolak-Wojciechowska, M. Wieczorek, A. Zwierzak, and S . Zawadski, J. Chem. SOC.,Perkin Trans. I , 1979, 146; G. S. Bajwa, W. G. Bentrude, N. S. Pantaleo. M. G. Newton, and J. H. Hargis, J. Am. Chem. Soc., 1979, 101, 1604. D. W. White, B. A. Karcher, R. A. Jacobson, and J. G. Verkade, J. Am. Chem. SOC.,1979, 101, 4921 ; A. Aaberg, T. Gramstad, and S. Husebye, Tetrahedron Lerr., 1979, 2263. H. W. Roesky, K. Ambrosius, and W. S. Sheldrick, Chem. Ber., 1979, 112, 1365; T. E. Clark, R. 0. Day, and R.R. Holmes, Inorg. Cham., 1979,18, 1653; J . V. Weiss, R. Schmutzler, D. Schomburg, and W. S. Sheldrick, Chem. Ber., 1979, 112, 1464. R . 0. Day, A. C. Sau, and R. R . Holmes, J. Am. Chem. SOC.,1979,101, 3790 A. Schmidpeter, J . H. Weinmaier, W. S. Sheldrick, and D. Schomburg, Z. Nafurforsch., Teil. B, 1979, 34, 906; W. S. Sheldrick, D. Schomburg, A. Schmidpeter, and T. von Criegern, Chem. Ber., 1980, 113, 55; H . J . Bestmann, K. Roth, E. Wilhelm, R. Bohme, and H. Burzlaff, Angew. Chem., Int. Ed. Engl., 1979, 18, 876. S . A. Shaidulin and V. A. Naumov, Z h . Srrukt. Khim., 1979, 20, 728 (Chem. Absrr., 1980, 92, 110429). L. L. Tuzova and V. A. Naumov, Z h . Srrukr. Khim., 1979,20,923 (Chem. Absrr., 1980,92, 146 849).

257

Physical Methods

A similar study of N(PFJ3 showed it to possess a planar CSh phosphacarbaborane l g o and HC-XPF, l g l have also been examined. Neutron diffraction has been used in the conformational analysis of phosphatidylcholine model

6 Dipole Moments, Kerr Effect, and Polarography Dipole Moments and Kerr Effect.-A combination of these techniques was used in the conformational analysis of aryl- and a-t hienyl-dichlorophosphanes ( RPCI,).lg3 Considerable attention has been given to stereochemical studies of compounds based on the I ,3,5-dioxaphosphorinan structure (74),78tl g 4 although work has also continued on the 1,3,2-dioxaphosphorinans(75).lI79lg5Interest has also been shown in the conformations of chloromethylpho~phinates,~~ pyrocatechol phosphites, l g 6 pyrazolyl- and triazolyl-ph~sphonates,~~~ and phosphoroAh initio calculations (with the inclusion of electronic sulphenyl configurations) on the dipole moments of H,PO, have been

Y

II

Ch

A r' , k H , A r2

Polarographic Studies.-The differential-pulse polarographic reduction potentials of triheteroarylphosphonium salts (76) correlated with the electron-accepting properties of the heteroaryl groups. Aryldiazidotris( piperidy1)phosphonium D. E. J . Arnold, D. W. H. Rankin, M . R. T o d d , a n d R . Seip, J . Chem. Soc., Dalton Trans., 1979, 1290. 1 9 0 V. S. Mastyukov, E. G . Atavin, I-. V. Vilkov, A . V. Golubinskii, V. N . Kalinin, G . G . Zhigarev, a n d L. I. Zakharkin, J. Mol. Struct., 1979, 56, 139. I o l H. Oberhammer, J. M o l . Struct., 1979, 53, 139. G. Zaccai, G . Bueldt, A. Seelig, a n d J. Seelig, J. Mol. B i d., 1979, 134, 693; G . Bueldt, H. U . Gally, J. Seelig, a n d G . Zaccai, ibid., p. 673. lg3 R. P. Arshinova a n d S. G. Vul'fson, Z h . Strukt. Khim.. 1979, 20, 862 (Chem. Ahstr., 1980, 92, 163 476). I Q 4 B. A. Arbuzov, 0. A. Erastov, S. N. Ignat'eva, T. A. Zyablikova, a n d R. P. Arshinova, Bull. Acad. Sci. U S S R , Dir.. Chem. Sci., 1979, 28, 1726 (Chcm. Ahstr., 1980, 92, 22 559); R . A. Arbuzov, 0. A. Erastov, a n d S. Sh. Khetagurova, Dokl. Akad. Nauk SSSR, 1979, 246. 326 (Chcm. Ahstr., 1979, 91, 140 193); I. I. Patsanovskii, E. A. Ishmaeva, N . M . Kudyakov, V. M. D'yakov, 0. A. Varnavskaya, M. G . Voronkov, a n d A. N. Pudovik, J. G m . Chem. (Engl. Transl.), 1979, 49, 2117 (Chem. Ahstr., 1980, 92, 75 716). l g 5 R. P. Arshinova, R . N. Gubaidullin, S. D. Ibragimova, a n d E. T. Mukmenev, Bull. Acad. Sci.U S S R , Dill. Chrm. Sci., I979,28, I408 (Chem. Abstr., 1979,91, 174 702) ;1. I. Patsanovskii, E. A. Ishrnaeva, B. Ziemnicka. M . Mikolajczyk, a n d A. N. Pudovik, J. Cen. C h ~ m . U S S R (Engl. Transl.), 1979, 49, 1459 (Chcm. Abstr., 1979, 91, 192 680). I g 6 B. A. Arbuzov, R. P. Arshinova, R . A. Kadyrov, a n d L. J. Gurarii, Bull. Acad. Sci. USSR, Dic-. Chcm. Sci., 1979, 28, 1869 (Chem. Abstr., 1980, 92, 58 070). 1 9 7 0. A . Samarina, E. A. Ishmaeva, a n d N. G. Khusainova, J. Cen. Chem. USSR (EngI. Trans/.), 1976, 46, 1708 (Chem. Ahstr., 1980, 92, 163 445). 1~ G. A . Kutyrev, A . I. Vinokurov, E. A. Ishrnaeva, I . K h . Shakirov, R. R. Shagidullin, R.A. Cherkasov, a n d A. N. Pudovik, J. G m . Chem. USSR (EngI. Transl.), 1979.49,458 (Chem. Ahsrr., 1979, 91, 19 821). 199 H. Wallmeier a n d W. Kutzelnigg, J . Am. Chem. Soc., 1979, 101, 2804. 200 D. W. Allen a n d L. Ebdon, Phosphorus Sulfur, 1979, 7 , 161. IHY

Organophosphorus Chemistrj*

258

salts are reduced in two one-electron waves, the second stage being determined by the proton donor (if one is present).2o1D.c. conductivity measurements in six alkyltriphenylphosphonium bis-quinodimet hanides have also been made.202

7 Mass Spectrometry Although this technique continues to play an important role in the characterization of organophosphorus compounds, there has been a reduction in the number of specific mass-spectrometric studies. An examination of the spectra of perfluoroaromatic compounds showed that fluorine has a tendency to migrate to the phosphorus atom.203Mass spectrometry of L-arabitol and ribitol diphosphites confirmed the presence of isomers.204The formation of two types of molecular ion upon electron impact on phosphorinones (77) has been proposed, one being of the type R,CO and the other PhP0.200"The mass spectra of the diphosphine disulphides (78) show that P C cleavage with loss of an R 2 group is followed by the elimination of R2PS, to give R1,PS+ as base peaks."06 Studies have also appeared on phosphorylated carbamates "07 and various phosphonates, phosphonothiolates, and phosphonofluoridates."On In the latter work, electronimpact and chemical-ionization spectra were studied. Field-desorption spectra were used in the determination of cyclophosphamide in biological media.2oos Phosphonopropionic acid was used as an internal standard for the quantitative estimation of phosphonoacetate by mass

R 8 pK,, Thermochemical, and Kinetic Studies The change in the acidities of diphenylphosphine, its oxide, and its sulphide from DMSO to DME media is far greater for the oxide. This has been attributed to a 201 20''

203 204

205

206

207

208 209 210

S. I. Petrov, V. N. Abramov, a n d L. A . Kazitsyna, J. Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 329 (Chrm. Abstr., 1979, 91, 4805).

R. Kowal a n d K. Lorenz, Pol. J. Chem., 1979, 53, 673. T. R. B. Jones, J . M . Miller, S. A. G a r d n e r , a n d M. D. Rausch, Can. J. Chem., 1979, 57, 335; H. R. H a n n a a n d J. M . Miller, ibid., p. 101 1 . Yu. Ya. Efremov, R . Z. Musin, E. T. Mukmenev, a n d N. A . Makarova, Khim. Geterotsikl. Soedin., 1979. 177 (Chem. Abstr., 1979, 91, 5428).

A. E. Lyuts, V. V. Zamkova, A. P. Logunov, Z. A. Abramova, B. M . Butin, a n d Y u . G . Bosyakov, Izr. Akatl. Nauk Kaz. SSR. Ser. Khim., 1979, 20 (Chem. AbFtr.. 1979, 91, 55 739). H. Keck a n d W. Kuchen, Org. Mass. Spectrom., 1979, 14, 149. V. A. Kolesova a n d Y u . A. Strepikheev, J. Gen. Chem. U S S R (EngI. Transl.), 1979, 49, 1943 (Chem. Abstr.. 1980, 92, 93 526). S. Sass a n d T. L. Fisher, Org. Mass Sprrtmni., 1979, 14, 257. H. R. Schulten, GC-MS News, 1979, 7 , 74. J . Roboz, R . Suzuki, R . Hunt, a n d J. G. Bekesi. Recent Drv. Mass Spectrom. Biochenr. Meci., 1979, 2, 205.

Physicul Methods

259

stronger anion-cation association for this compound."' The relative basicities of ylides have been briefly reviewed, and Hammett substituent constantscornpared. 2 1 The pKa values of the cyclic esters (79; Y = CO,R or CN),213the a-nitroalkyl compounds (80; Y = Ph, Et, or OR),214and the thioamides (81)215 have been recorded and studied. Steric as well as inductive and resonance effects are required to give an adequate mathematical description of the dissociation constants of the phosphorus acids (82).216 The acidities of Pv hydroxyphosphoranes are relevant to studies of the hydrolysis of phosphorus compounds. The pKa values of the phosphoranes (83) and (84) were estimated from their equilibria with weak acids and the properties of their amine complexes. Quite large differences were observed; thus, whilst (83; Y = Me) had pKa 10-1 1, the trifluorocompound (83; Y = CF,) had pKa 5.3, and the carboxy-derivative (84) was even more acidic than the latter trifluoro-compound. The thermal transitions of a variety of phosphines, salts, and esters have been studied by d.t.a.218Phosphoric acids have been studied with regard to their , ~ ~ ~ of neutralization,220and thermostandard enthalpies of c o m b u s t ~ o n heats 0

I1

LZYp\CH2Y

(79)

0

I1

i

Y,PCH R NO,

Et,PNHSO,Ar

(80)

(81)

Y 2 / 'OH

0

OL1

2'2

213 "1'

215 216

217 218

219 ~

(

E. S. Petrov, M . 1 . Terekhova, 1. G. Malakhova, E. N . Tsvetkov, A. 1. Shatenshtein, and M . I . Kabachnik, J . Gen. Chem. USSR (Engl. Transl.), 1979,49, 2127 (Chem. Abstr., 1980, 92, 128 21 I ) . I . N. Zhmurova, R . I . Yurchenko, A . A . Tukhar, V. G . Yurchenko, and 0. M . Voitsekhovskaya. J. Gen. Chvm. U S S R (EngI. Transl.), 1979, 49, 2119 (Chem. Abstr., 1980, 92, 93 499). V. V. Ovchinnikov, V. M . Valitova, R. A. Cherkasov, and A. N . Pudovik, J. Gen. Chem. USSR (Engl. Transl.), 1979, 49, 2148 (Chem. Abstr., 1980, 92, 110 377). K . A. Petrov, V. A. Chausov, N . N. Bogdanov, and S. V. Agafonov,J. Gen. Chem. USSR (Engl. Transl.), 1979, 49, 75 (Chem. Abstr., 1979, 90, 187 049). L. Almasi and R. Popescu, Rec. Roum. Chim., 1979, 24, 741. V. A . Baranskii and B. I. Istomin, J . Gen. Chem. USSR (EngI. Transl.). 1979, 49. 409 (Chvm. Abstr.. 1979, 90, 203 327). I . Granoth and J . C. Martin, J. Am. Chem. SOC.,1979, 101,4618; Y .Segall and I . Granoth, J . Am. Chem. Soc.. 1979, 101, 3687,4618. G . V. Romanov, A. N . Pudovik, R. Ya. Nazmutdinov, V. M . Poshidayev, and A. A . Lapin, J . Therm. Anal., 1979. 16, 103. P. C. Schulz, Bol. SOC.Quim. Peru, 1978, 44, 92 (Chem. Abstr., 1979, 91, 38 732). V. 1 P. Vasil'ev, L. A. Kochergina, M. V. Rudomino, and N . V. Nichugina, J. Gen. Chem. USSR (Engl. Transl.), 1979, 49, 1803 (Chem. Abstr., 1980, 92, 75 623).

260


dynamics of micellization.221Some heats of complexation of phosphites with fluoroalkyl iodides 2 2 2 and with SnCI, 223 have also been reported. Thermodynamic parameters have been obtained from kinetic studies of the transesterification of an aryl phosphinate 224 and of addition reactions of dialkyl phosphites to Schiff bases.225Correlation analysis has also been applied to the latter reaction 226 and to the reaction of triphenylphosphine azo-ester with 3hydroxycarboxylic acids in a comparison of hydroxylic- and carboxylic-group activation.227The additive effects of changing the substituents on phosphorus have been evaluated for the rates of alkaline hydrolysis of thep-nitrophenyl esters (85),22s the acid fluorides (86),229 and some other acid halides.230Many other kinetic studies have been published, many of which are discussed in the previous chapters.

9 Chromatography G.1.c.-A glow ionization detector for nitrogen and phosphorus compounds has been described.231Further work has been published on the g.c. analysis of the trimethylsilyl derivatives of phosphonic and phosphinic acids 2 3 2 and on the g.c.-m.s. analysis of steroids, using their dimethylthiophosphinic There have been several studies of g.c. and g.c.-m.s. determinations of organophosphorus pesticides 234 and derivatives of methylphosphonic acid in surface water.235The P. C. Schulz and A . L. M. LeLong. An. Asoc. Quim. Argent., 1978, 66, 1 I (Chem. Ahstr., 1980,92,29 044). 222 A. V. Garabadzhin, V. A . Kuznetsov, V. 1. Shivaev, A. N. Lavrent’ev. and E. G . Sochilin, J . Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 1952. 223 L. V. Kucheruk, 1. P. Gol’dshtein, E. S. Shcherbakova, E. N . Gur’yanova, I . Ya. Kuramshin, and A. N. Pudovik, J . Gen. Chem. USSR (Engl. Transl.), 1979,49, 6 4 3 . 2z4 G. L. Matevosyan and P. M. Zavlin, J . Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 1099. 225 G . A. Gartman, V. D. Pak, and N. S. Kozlov. J . Gen. Chem. U S S R (Engl. Transl.), 1979, 49, 2095 (Chenr. Ahslr., 1980, 92, 128 009). 2213 G . A. Gartman, V. D. Pak, and E. V. Simonova, J . Gen. Chem. U S S R (Engl. Transl.), 1979,49, 2295 (Chem. Absrr., 1980,92, 110 380). 227 J. Mulzer, G. Bruentrup, and A . Chucholowski, Angew. Chem., Znr. Ed. Engl., 1979, 18, 221

622.

228 229

V. E. Bel’skii, L. A. Kudryavtseva. 0. M . Il’ina, and B. E. Ivanov, J . Gen. Chem. USSR (EngI. Transl.), 1979, 49, 2180. B. I. istomin and V. A. Baranskii, Urg. Reuct. (Tartu), 1978, 15, 291 (Chem. Ahstr., 1979, 91, 38 474).

230 231 232

233 234

V. A . Baranskii and B. I . istomin, J. Gen. Chem. USSR (Engl. Transl.), 1979, 49, 1030 (Chem. Abstr., 1979, 91, 56 094). P. L. Patterson, Ger. Offen. 2 907 222 (Chem. Ahstr., 1980, 92, 140 136). L. Gasco, R. Barrera, A . Ramirez, and M. N. Martin, Chem. Abstr., 1979, 91, 67 993. K. Jacob, W. Vogt, G. Schwertfeger, E. Maier, A. Ohnesorge, and M. Knedel, Chem. Ahsfr.. 1979, 91, 189 052. J . A . Auh, C . M. Schofield, L. D. Johnson, and R. H. Waltz, J . Agric. Food Chem., 1979, 27, 825; R. Mestres, S. Atmawijaya, and C. Chevallier, Ann. Faisif. Expert. Chim., 1979, 72, 577 (Chem. Ahsrr., 1980, 92, 145 073); C. E. Johansson, Pestic. Sci., 1978, 9, 313; H . J. Stan. Lehensmittelche.nr. Gerichtl. Chem., 1979, 33, 54 (Chem. Ahstr., 1979, 91, 138 950).

23s

A. Verweij, C . E. A . M . Dogenhardt, and H. L. Boter, Chemosphere, 1979, 8, 115.

Physical Methods

26 1

technique is also finding wide application in the determination of drug metabolites and naturally occurring phosphates in biological T.1.c.-In the wide application of t.1.c. to the analysis of biological of special interest is the use of a tubular apparatus. The eluted compounds are volatilized at the end of the tube in a ring furnace and detected by FID.23*A study of the t.1.c. behaviour of dioctyldithiophosphinic acid has also been reported.239 H.p.1.c.-A reversed-phase analysis of phosphine oxides and various phosphorus acid esters utilizes aqueous methanol as the mobile phase.24oH.p.1.c. has been extensively applied to biological systems. 24

Column and Gel Chromatography.-The identification of organophosphorus compounds (especially aminophosphinates) has been reviewed. 242 Most biological applications involved ion-exchange resins.243The separation of phosphinates, phosphonates, and orthophosphates by gel chromatography has been described. 244

2x7

238

239 240 241

242 243

244

J . Roboz, R. Suzuki, and E. Rose, J. Chromatogr., 1980, 181, 195; J . M. Strong, Y. E. Kinney, A. R. Branfman, and R. L. Cysyk. Cancer Treat. Rep.. 1979, 63, 775; C . A . Shively, R. J. Simons, and E. S. Vesell, Pharmacology, 1979, 19, 228; R. A. Rockerhie, R. D. Dobson, and J. Frohlich, Clin. Chem. ( Winyton-Salem, N.C.), 1979, 25, 141 1 ; M. S. Nayar, L. Balachandran, W . Lo-Yin, H. Suk, and K. K. Chan, Anal. Lett., 1979, 12, 905. J . Dutta, A. K. Das, and A. Biswas, J. Chromatogr.. 1979, 173, 379; J. Cadet and L. Voituriez, ibid., 1979, 178, 337; M . Jarman and W. J. Stec, ibid., 1979. 176, 440; V. E. Vas’kovskii, N. A. Latyshev. and E. N. Cherkasov, ibid., p . 242; V. E. Vas’kovskii and T. A . Terekhova, HRC CC, J. High Resolur. Chromatogr. Chromatogr. Commun., 1979, 2. 671. 0. Adam, G . Wolfram, and N . Zoellner, Chromatogr. S v m p . Ser., 1979. 1, 267 (Chem. Ahstr., 1979, 91, 52 071). 0. M. Frid-Dymkina, N. M . German, and S. N. Ryabchenko, I n . Sib. Old. Akad. Nauk S S S R , Ser. Khim. Nauk, 1979, 13 (Chem. Abstr., 1980, 92. 6613). D. L. Manning, Chem. Ahstr., 1980, 92, 137 3 I I . C. Garrett and D. V. Santi, Anal. Biochpm., 1979,99,268; P. V. Bhat, L. M. De Luca, and M. L. Wind, ibid., 1980, 102. 243; K . Ishii, K . Sarai, H. Sanemori, and T. Kawasaki, [hid., 1979, 97, 191; M. Kimura, T. Fujita, S. Nishida. and Y. Itokawa, J. Chromatogr.. 1980, 188,417; D. Mauro. D. Wetzel, C. H. Lee, and P. A. Seib. ihid., 1980, 187, 421; S. S. Kent and B. C. Hemming, ihid., 1979, 177. 372. A. Hayashi and F. Matsuura, Chem. Ahstr., 1980, 92, 2552. H. W. Heldt, A. R. Portis, R. M. Lilley, A. Mosbach, and C. J. Chon, Anal. Biochem., 1980, 101, 278; W. Sasak, C. S. Silverman-Jones, and L. M. De Luca, ibid., 1979, 97, 298; A. D. Gounaris and M. Schulman, ibid., 1980, 102, 145; G . Alberti, U. Costantino, and M. L. L. Giovagnotti, J. Chromatogr., 1979, 180.45; V. Svoboda and 1. Kleinmann, ibid., 1979, 176, 65. K. Ujimoto, 1. Ando. T. Yoshimura, K . Suzuki. and H. Kurihara. J. Chromatogr., 1980, 190, 161.

Author Index

Aaberg, A., 256 Abalonin, B. E., 60 Abbott, P. J., 198 Abbott, S. J., 97, 127 Abdallah, M. A., 128 Abdul Malik, K. M., 22 Abe, N., 10 Abel, E. W., 29 Abeysekera, B., 231 Abdurashidova, G. G., 189 Abicht, H-P., 21 Abramov, V. N., 28, 258 Abramova, Z. A., 258 Achinami, K., 10 Ackerman, J. J. H., 6 Ackrell, J., 17 Adachi, M., 18, 62 Adam, O., 261 Adam, W., 18 Adamiak, R. W., 194 Adams, M. J., 128 Adams, R. D., 256 Adams, W. E., 18 Adiwidjaja, G., 245 Afanas’ev, M. M., 242 Agafonov, M. N., 17, 41 Agafonov, S. V., 259 Agaichi, T., 128 Agarwal, K. L., 197 Agarwal, R. K., 75 Agawa, T., 105, 231 Agranat, I., 236 Ahlers, H., 66 Ahmed, M., 8 Aiba, H., 188 Aida, K., 251 Aizenshtat, Z., 21 Akiba, K., 75 Aladzheva, I. M., 48, 242, 254 Alayoff, A., 137 Alberti, G., 261 Alder, L., 252 Alekseeva, 0. T., 71 Alekseev, V. I., 254 Alexanian, V., 28, 40 Alfer’ev. I. S.. 121 M.; .:6 Ali, A. A. M Ali, S. M., 234 Ali; Allen, D. W., 12, 25, 28, 31, 74, 209, 257 Allfrey, V. G., 178 Almasi, L., 111, 120, 242, 244. 259 Alsaidi, H., 12 Al-Salem, N. A., 2 Al-Shamman, A. J. N., 133 Altenbach, H. J., 218 Altukhov, K. V., 122 Alyea, E. C., 21 Amarskii, E. G., 75

Ambrosius, K., 32, 48, 256 Aminova, R. M., 242 Ambartsumyan, N. S., 201 Amsler, P. E., 154 Ando, I., 261 Andreev, N. A., 46 Andriamizaka, J. D., 20 Andrianov, V. G., 256 Angelov, Kh. M., 102, 123, 124 Angstrom, J., 137 Annesley, T. M., 141 Antczak, K., 107 Antipin, M. Yu., 254, 255 Antoniadis. A.. 20 Antropova; E. ’I., 251 Aoki, K., 130 Appel, R., 14, 19, 21, 33, 58, 209, 245 Arai, Y., 171, 215 Aradi, J., 198 Arbuzov, B. A., 10, 12, 17, 41, 77, 246, 251, 254, 257 Arcamone. F.. 211 Archibald?‘I. G., 128 Arentzen, R., 19 Armitage, I. M., 127 Armstrong, V. W., 185, 190 Arnold, B., 222 Arnold, D. E. J., 46, 257 Arpac, E., 6 Arshinova, R. P., 46, 251, 257 Ashton, W. T., 130 Aslanov, Kh. A., 189 Aslanov, L. A., 246, 255 Ashe, A. J., 253 Ashrafullina, L. Kh., 251 Astell, C., 201 Atabekov, J. G., 200 Atavin, E. G., 257 Atkinson, J. G., 214 Atkinson, T. C., 195 Atmawijaya, S., 260 Atovmyan, L. O., 255 Atwood, L., 143 Auerswald, C., 24, 119 Ault, J. A., 260 Avdonina, T. A., 201 Avery, M. A., 238 Aviron-Violet, P., 6 Ayi, A. I., 62 Azerad, R., 131 Baacke, M., 7 Baban, J. A., 248, 249 Baboulene, M., 77, 106 Babu, Y. S., 256 Baburina, V. A., 115 Baccolini, G., 41, 80 Badanyan, Sh. O., 123

262

Baggott, J. E., 141 Bagrov, F. V., 52, 121 Bahl, M. K., 253 Bajwa, G. S., 256 Bakakin, V. V., 254 Baker, J. R., 246, 255 Balachandran, L., 261 Balaram-Gupta, B. G., 17 Balci, M., 18 Balczewski, P., 106 Baldwin, J. J., 15 Balitskii, Yu. V., 41, 49, 251 Balkunova, V. P., 126 Balthazor, T. M., 122 Baltzinger, M., 190 Bamgboye, T. T., 256 Banas, E. M., 142 Banek, M., 32,48 Bannwarth, W., 173 Barabas, A., 111, 244 Baraniak, J., 98, 173, 174, 175, 245 Baranov, A. P., 74 Baranov, G. M., 120 Baranskii, V. A., 259, 260 Barany, M., 240 Barcelos, F.,234 Bard, R. R., 79 Bardos, T. J., 168, 198 Bariou, B., 12 Barlev, A. A., 250 Barlos K., 246 Barna;d, D. W. C., 143 Barnes, C. L., 256 Barnet. B. L.. 136 Barrans, J., 36 Barrera, R., 260 Barrio, J. R., 171, 187 Barry, B. V. L., 241 Barrv. S.. 127 Barth; V.’,19, 58, 245 Bass, M. A., 138 Bassett, J. M., 224 Baudler, M., 7, 53, 56 Bauer, L., 173 Baughman, M., 187 Baum, H., 190 Baxter, A. J. G., 211 Bayandina, E. V., 55, 252 Beaucage, S. L., 194 Beauchamp, J. L., 253 Beaucourt, J.-P.. 175 Beavo, J. A., 138 Bechtolsheimer, H.-H. Beck, W., 4 Becker, G., 19, 57 Becker, J., 207 Becker, M. A., 136 Beckman, D. E., 256 Beechey, R. B., 190 Beer, P. D., 32, 77

Author Index Begley. M. J., 256 Beheir, S. G., 75 Bekeci, J. G., 258 Bel, V. K., 102 Belagaje, K., 195 Belkin, Yu. V., 12 Bellaart, A. C . , 254 Belleau. B.. 113. 173 Belostotskaya, I. S., 35 Belskii. V. A., 4 2 Bel’skii, V. E., 110, 241, 251, 253. 260 Belostotskaya, I. S., 250 Benavides, J., 139 Bender, M . L., 143 Renkovic, P. A., 112, 135 Benkovic, S. J., 112, 135, 136, 167, 183 Benovic, J. L., 179 Bentrude. W. G., 37, 256 Berclaz, T., 249 Berdnikov, E. A., 122, 124 Berestovitskaya, V. M., 106 Berger, H . O., 246 Berkenhoff, H. O., 5 8 Berlin, K. D., 246, 255 Bernardinelli, G., 7 4 Bernard-Moulin, P., 240 Bernasconi, S., 126 Besse, J . J., 24 Bessman, S. P., 141 Bestmann. H. J.. 22. 23. 32. 207, 210, 216, 221, 223; 233, 256 Bhakta, C., 234 Bhat. P. V.. 261 Bhooshan, B . , 199 Biala, E., 198 Biebricher, C. K., 186 Biellmann, J. F., 128 Bigge, C. F., 171 Bikeev, Sh. S., 4 7 Biran. Z., 244 Biro, V., I20 Bisswanger, H., 137 Biswas, A., 261 Blackburn, G. M., 109 Blattler, W. A., 182 Blaicher, W., 32 Blake, A. J., 7 4 Blakeley, R., 144 Blakeley, R. L., 128 Blanquet, S., 190 Blaschke, G., 22, 224 Blocker, H.. 193 Blum, J., 17, 21, 106, 120 Blustin, P. H., 240 Bocelli, G . , 6 Bockhoff, F. M., 97, 127 Bodalski, R., 64 Bodor, N., 9 9 Bodrin, G. V., 7 5 Bohme, R., 32, 216, 256 Boev, V. I., 79 Bogdanov, A . A., 200 Bogdanov, N. N., 259 Bogel’fer, L. Ya., 246 Boguski. M . S., 201 Bohlmann, F.. 238 Bohnisch, V. W., 85 Bokanov, A. I., 243, 252 Boldeskul, I. E., 251 Boldyrev, I. V., 105

263 Bolen, D. W., 185 Bomben, K. D., 253 Bon. M . , 251 Bondar, S. V., 122 Bondarenko, N . A., 4 Bonini, B. F., 223 Bonnet, P., 240 Bonningue, C., 246 Boots, S. G., 237 Bordner. J., 217 Borek, E., 188 Borisenko, A. A . , 96, 245, 246 Boskakova, Z. M., 252 Boswell, K. H., 175, 176 Bosyakov, Yu. G., 258 Boter, H. L., 260 Bottka, S., 165 Bottin-Strazalko, T., 206, 246 Bouchu, D., 114 Bouissou, T.. 251 Boundr. D. G., 248 Bovin, J. O., 256 Boyd, V. L., 99, 256 Boyer, M., 249 Branden, R., 137 Bramson, H. W., 185 Branch, C. L., 211 Brandstetter, H. H., 16 Branfman, A. R., 261 Brazier, J. F.. 246 Becker, G., 254 B redikhina, Z. A., 122 Brel. V. K., 103 B reque. A., 105 B reuer, E., 34 B rierley, J., 40, 243 B right, H. J., 129 Brimacombe, R., 201 Brintzinger, H., 154, 155 B rodack, J . W., 7 Brody, R. S., 177 Broekhof. N . L. J. M.. 52. 66, 227’ Brokaw, F. C., 235 Bronder, M., 222 Brosche. T.. 233 Brouillette, ’C. B., 168 Brown, C., 91 Brown, D. H., 18, 67 Brown, D. M., 143 Brown, E. L., 195 Brown, F. F., 240 Brown, I., 140 Brown, J. M., 4, 6 Brown, L., 235 Brown, R. D., 130 Brown, S. B., 5 , 254 Brown, T. R., 127, 240 Brownlee, G. G., 200 Brownstein, S., 20, 246 Brousseau, R., 195 Briintrup, G., 16,260 Brunner, H., 6, 8, 92 Brunnhuber, G., 30 Bruzik, K., 98, 117 Bryan, D. B., 215 Bryant, F. R., 183 Bryant, J. D., 171 Brzezinska, Z. C., 7 Bubnov, N. N., 249,250 Buchanan, G. W., 245

Buchholz, M., 24 Buck, H. M., 254 Buckler, S. A., 63 Budowsky, E. I., 189 Bueldt, G . , 257 Buerkle, W., 16 Buicong, C.. 42 Buina, N. A.. 109, 253 Buisson. D. H., 154 Bukachuk, 0.M., 24 Bunnett. J . F.. 79 Bunton,’C. A., 143 Burgada, R., 12, 32, 36, 37, 39. 78. 207. 247 Burger, K.,32 Burgers, P. M. J., 175, 183, 184 Burmester, A., 38 Burnaeva, L. A . , 77, 108, 109 Burt. C. T.. 240 Burt, R. J., I Burton, D. J., 13, 42, 58, 208 Burton. J. J.. 208 Burzlaff, H.,’ 32, 216, 256 Busch, H., 138 Busch, K . H., 7 0 Buslaeva, G. E., 12 Butcher, W. W., 143 Butin, B. M., 258 Butler, I . S., 250 Butler, L. G., 135 Butler, R . N., I19 Butterfield. P. J.. 247 252 Bychkov, N. N.,’ Byers, L. D., 137 Bykova, T. G., 42 Bystrov, N. S., 192 Cadet, J., 261 C a h a y , R., 60 Caldwell, A. G., 234 C a m a , L., 211 C a m e r o n , A. F., 255 C a m e r o n , I . R., 255 C a m e r o n , T. S.. 100, 246 Campbell, 1. D., 127 Campbell, M. M., 108 Cancellieri, G., 6 2 C a n e , D. E., 128 Canevet, C., 233 C a p u a n o , L., 222 Carey, D. J., 130 Carey, L. W., 7 Carlsohn, B., 56 Carpenter, L. E., 254 Carrie, R., 77, 214 Carroll, A. R., 178 Carroll. C.. 197 Carruthers; N., 108 Carsky, P., 215 Carter, R . O., 252 Cartwright. 1. L.. 198 C a r t y , A. J., 7, 21 Caruthers, M. H , , 195 Cashion, P., 178 Cassidy, P. S., 185 Castillo, M. J., 254 Castro, B., 14, 39, 87 Cavanga, F., 71 Cavell, R. G., 243 Cavezzan, J., 20, 57 Cavicchio, G., 23, 206 Cepulis, R. L., 232

264 Cerri, V., 249 Chabrier, P., 110 Chabrier. P. E.. 110 Chachaty, C., 240 Chafiin. V. J. K., 6 Chan, D. M. T., 26, 219 Chan, K. K., 261 Chang, B. C., 132 Chang, C. T.-C., 167, 168 Chapleo, C. B., 234 Chapleur, Y., 14, 39, 87 Charollais, E. J., 64 Charrier, C., 31, 73, 105 Charubala, R., 173, 196 Chassignol, M., 110, 191 Chatt, J., 1 Chattopadhyaya, J. B., 191, 197

Chaidhry, S. C., 75 Chauzov, V. A., 8, 69, 73, 104. 259 Chaw; Y. F., 143 Chawla, R. R., 188 Chefczynska, A., 106, 226 Chen, C. H., 224 Chen, C.-T., 99 Chen, J.-T., 244 Chen, M. S., 164 ChCne, A., 24 ChereDinskii-Malov. V. D.. 254' Cherkasov, E. N., 261 Cherkasov, R. A., 115 , 116, 120. 257. 259 Cherkasov,' V. M., 105 Chernii, V. N., 52, 103 Chernobrovkina, L. P., 8, 73 Chernokal'skii, B. D., 45,60, 68, 242, 248 Chernova, A. V., 252 Chernov, B. K., 192 Chesnut, D. B., 1 Cheung, C. P., 128, 129 Cheung, H. S., 134 Cheung, Y-F., 237 Chevallier, C., 260 Chibirova. F. Kh.. 252 Chichkova, N. V.,' 200 Chiles, M. S., 24 Chistokletov, V. N., 3, 49 Chittenden. R. A,. 125 Chizhov, V'. M., 108, 122 Chlebowski, J. F., 127 Chmutova, M. K., 75 Chodkiewicz, W., 2, 3, 15, 5 5 , 94 Chodosh, D. F., 256 Choi, S., 168 Chon, C. J., 261 Chou, S.-S. P., 5 Choplin, F., 240 Chretien, F., 14, 87 Christensen, B. G., 211 Christensen, L. F., 175 Christmann, K. F., 237 Christol, H., 22, 23, 24, 26 Chucholowski, A., 16, 260 Chunin, E. D., 123 Chuprakova, K. G., 52, 103, 104 Ciampolini, M., 5 Clark, D. A., 215 Clark, D. S., 18

Author Index Clark, N., 29 Clark, P. W., 4, 5 5 Clark. T. E.. 256 Clark; V. M:, 140 Clarke, S. D., 211 Clausen, K., 125 Clef, E., 7 Cleland, W. W., 136, 178, I79 Clive. D. L. J., I18 Cloudsdale, I . S., 228 Clough, J. M., 236 Coates, H., 91 Cocco, L., 128 Coderre, J. A., 98, 166, 174, 175 Coetzee. J. F.. 146 Cogne, A.,245 Cohen, N., 238 Cohen, S. M., 127, 240 Cohen-Solal. M.. I39 Cohen-Solal; L.,'l39 Cohn, M., 180, 182, 184,241 Cohn, W., 137 Cole-Hamilton, D. J., 2 Coleman, J. E., 127 Colleuille, Y., 6 Collier, K. J., 194 Collingnon, N., 108 Colvin, E. W., 228 Comini, A., 126 Comins, D. L., 230 Conant, J. B., 153 Condom, R., 62 Cong, C. B., 83 C6ng-Dach, N., 175 Connor, J. A., 79 Cook, A. A., 153 Cook, W. H., 154 Cooksey, C. J., 248 Cooper, D., 86 Cooper, T. A., 20 Coppola, G. M., 109 Corbella, A., 126 Cordes, A. W., 254 Cordes, R. E., 100, 247 Corey, E. J., 215, 234 Corey, R. M., 26 Cornell, N . W., 141 Corset, J., 206, 246 Cory, R . M., 219 Cosslett, L., 13 Costantino, U., 261 Couret, C., 20, 57 Cowley, A. H., 19, 24 Coyne, B. B., 153 Cozens, R . J., 32, 77 Cozzi, F., 243 Crabtree, R. H., 21 Cramer, F., 188 Crea, R., 196 Cristau, H.-J., 23, 24,26,222 Cross. R. J.. 18. 67 Crossland, N. M.,234 Crothers, D. M., 200 Csizmadia, 1. G., 244 Cullen, W. R., 2 , 7 Cunkle, G. T., 1 Cuppens, T. J. H. M., 130 Currie, B. L., 173 Cushman, D. W., 134 Cushner, M. C., 19, 24 Cyskt, R. L., 261

Dagnac, P., 246 Dahl, O., 3, 141, 254 Dahlenburg, L., 6 Dahlqvist-Edberg, U., 138 Dakternieks, D., 37, 39 Danchenko, M. N., 97 Dangyan, Yu. M., 123 Danilenko, V. A., 12 Danilov, N. A., 75 Dankowski, M., 21 Dannhardt, G., 71 D'Antonio, M., 23 Dapporto, P., 5 Das, A. K., 261 Dashevskii, V. G., 74 Datta, P., 1 13, 173 Davalian. D., 236 David, S., 213 Davidson, D. W., 60 Davidson, G., 251 Davidson, R. M., 106 Davis, R. E., 5, 254 Davis, S. G . , 13 Day, R. O., 32, 256 Dean, P. A. W., 75 Deck, J. R., 171 d e Clercq, E., 168, 199 Declercq, J. P., 125 Deger, H. M., 236 d e Groot, E. J., 188 Dehnel, A., 232 Dehnert, P., 250 d e Lauzon, G., 29, 254 D e Luca, L. M., 261 Demir, T., 100, 247 Demuth, R., 250 Denerley, P. M., 84 den Hartog, J. A. J., 196 den Hollander, J. A., 127 Denis, J . N., 55 DePaoli-Roach, A. A., 138 Derbyshire, R. B., 191 de Rooij, J. F. M., 194, 195 De Ruiter, B., 256 Desai, N. B., 142 Descamps, J., 168 Deschamm. B.. 29. 254 Deschler,'U., 209 Deutsch, E., 136 DeWolf, W. E., Jr., 169 Dhar. R.. 200 Dianova.' E. N.. 254 Dias, S. A., 21 Dickstein, J. I., 27, 40, 243 Diemart. K.. 125 Dimroth, K.',31 Di Sabato, G., 143 Dissing, J., 141 Dittebrandt, C., 60 1Divisia, B., 245 1Dixneuf, P. H., 21 IDiokar. K.. 222 1Dmitriev, V. I., 60, 61, 251, 252 aobrynin, V. N., 192 Klobson, R. D., 261 Dodonov. A. M.. 59. 252 Doe, H., 75 Dogadina, A. V., 47, 88, 102, 103, 123 Dogenhardt, C . E. A. M., 260 Dolinnaya, N. G., 197 '

'

I

.

Author Index Dombrovskii, A. V., 79 Donis-Keller, H., 200 Donovan, S. F., 238 Dooijewaard, G., 138 Doornbos, J.. 196 Dormoy, J. R., 39 Dorokhova, V. V., 251 Doroshkina, G. M., 252 Dose, K., 189 Dougherty, D. A., 243 Douglas, J. E., 113 Drabarek, S., I Drabikowska, A. K., 169 Drabowicz, J., 244 Drach, B. S., 26 Drenth, W., 1 1 Dreux, J., 114 Drews, R. E., 113, 256 Driehsen, W., 7 Dubac, J., 20, 57 Dubenko. L. G... 61., 248 Duchek, I., 9 Dudchenko, T. N., 117 Dudvcz. L.. 169. 170 Dumm,’H. ’V., 38, 245 DuMont, W. W., 14, 19 Dunaway-Mariano, D., 178, I79 Dunning. V. D.. 250 Durig, f.’ R., 250, 252 Dutka, F., 111 Dutasta, J. P., 247,255 Dutta. J.. 261 Duttmann, H . , 213 Dyadin, Yu. A., 254 D’yakov, V. M., 10, 257 Dyer, T. A., 200 Ealick. S.-E..246. 255 Eapen; K. C:, 2 . Earnshaw, C., 65, 228 Eatovskii. G. V.. 101 Ebdon, L:, 28, 257 Eberle, H . - J . , 95 Ebsworth, E. A. V., 209 Eckstein, F., 175, 178, 183, 184, 185, 190 Eckstein, V., 121, 232 Edelman, K., 188 Edge, M. D., 195 Edmondson, D. E., 127 Edwards, M. W., 167 Edwards, R. C., 32, 77 Efremov, A. I., 47, 60, 106, 242. 248 Efremov, Yu. Ya.. 258 Egan, W., 118 Egorov, Yu. P., 244, 251, 255 Ehehalt, R., 247 Eilets, H., 256 Einstein, F. W. B., 2 Eirich. L. D.. 130 Ekrnan, P., 1‘38 El Abadelah, M. M., 83 Elepina, L. G., 255 Elepina, L. T., 246 Eliseeva, G. D., 126 El Khoshnieh, Y.O., 12, 32, 37, 78, 207 El’natanov, Yu. I., 10 Empsall, H. D., 2 Enda, J., 105

265 Enda, T., 231 Engelhardt, G., 24, I19 Ennelhardt. V.. 247 Engels, J., 196’ Engle, T. W., I18 English, A. D., 248 Engstrom, L., 138 Ennen, J . , 4 Epstein, M., 63 Erastov, 0. A., 10, 246, 257 Erben, D., 171 Erernenko, M . V., 23 Eriksson, B., 138 Ermolaeva, L. V., 253 Ernst, L., 224 Ernst, V., 138 Erokhina, T. S., 69 Ershov, V. V., 35, 250 Escudie, J., 20, 57 Eshaghpour, H., 200 Eshtiagh-Hosseini, H., 20, 246 Ettlinger, M., 210 Eustache, J., 21 3 Everard, R. A., 135 Evstaf’ev, G. I., 121 Fabas, C., 36 Fadel, A., 218 Faehl, L. G., 22 Faggiano, M., 80 Fallouh, F., 26 Fasiolo, F., 190 Faskhutdinova, T. A.. 108 Fatkhullin, R. M., 47 Fauduet, H., 39 Fayat, G., 190 Fayos, J., 256 Fedan, J. S., 189 Fedin, E. I., 48 Feitler, D., 10 Felcht. V. H.. 71 Feldmann, K:, 130 Felkin, H . , 21 Fendler, E. J., 143 Fendler. J . H.. 143 Fenesan, I., 120 Feramisco, J. R., 139 Feshchenko, N. G., 45, 55, 60, 68 Fiaud, J . C., 6 Ficcadenti, P., 62 Fiel, R. J., 198 Fild, M . , 6, 227, 241 Filippov, E. A., 75 Fillebeen-Khan, T., 21 Finch, A., 60 Finch, M. A. W., 234 Findlay, J. B., 112 Finnan, J. L., 196 Fiorini, M., 10 Fischer, J., 29, 254 Fisher, T. L., 258 Flemal, J . , 125 Fleming, M . P., 230 Flitsch, W., 219 Florent’ev, V. L., 172,186 Flores, R. A., 122 Fluck, E., 89 Foglio, M., 211 Fokin, A. V., 101 Font Freide, J . J . H . M., 44 FOSS,V. L., 53, 68

Foster, A. B., 100, 140 Foucaud, A., 15, 81,88,206, 226 Fox, M. A., 21, 207 Franceschi, G., 21 1 Francot, J., 75 Frank, A., 255 Frank, A. W., 26 Frank, J., 1 1 I Franks, S.,1, 64 Fraser, A. R., 195 Fraser-Reid, B., 235 Frazier, W. A., 188 Frev. P. A.., 128., 129., 138., 182, 183 Frjdland, S. V., 47, 60 Friebe, S., 11 Frieden. C.. 169 Fritschel, S: J., 6 Fritz, G . , 7, 58 Frohlich, J . , 261 Froment. F.. 206. 246 Froussios, C., 131 Frickel, F., 227 Fridey, S. M., 256 Fridland. S. V.. 242. 248 Frid-Dymkina,’O. M.,261 Freist, W., 188 Frey, P. A., 190 Fueller, H. J., 255 Fujino, S., 31 Fujisawa, Y., 164 Fujita, S., 28, 253 Fujita, T., 261 Fujitaki, J., 188 Fukata, G., 2 Fukuda, K., 164 Fukumoto, R., 199 Fukui, T., 199 Fukushirna, M., 10 Fuller, C. W., 129 Fullin, F. A., 169 Furin, G. G., 62 Futatsugi, T., 82, 129, 154 Fuzhenkova, A. V., 77 Gaidai, V. I., 107 Galakhov, M. V., 244 Galdecki, Z., 64,73, 255,256 Galeazzi, E., 17 Galkin, V. I., 120 Galkina, N. E., 121 Gallagher, M. J., I , 255 Gallapo, A. R., 136 Gallo. R.. 12 Gally; H.’V., 257 Galpin, I. J., 18 Galushina, V. V., 117 Galv. J.. 256 Gamayurova, V. S., 68 Ganoza, M . C.. 195 Gara, W. B., 248 Garabadzhin, A. V., 260 Garaeva, L. D., 165 Gardner, S. A., 258 Gareev, R. D., 41, 121, 123 Garegg, P. J., 15 Garibaldi, P., 126 Garibina, V. A., 123 Garrett. C.. 261 Garrigues, B., 36, 37, 42, 83, 88, 92 Garst, M., 237

266 Gartman, G. A., 260 Gasco, L., 260 Gates, P. N., 60 Gaudiano, G., 23, 206 Gautheron, B., 29 Gavrilov, V. I., 45 Gazizov, M. B., 52 Gazizov, T. Kh., 39 Gazzola, C., 141 Geahlen, R. L., 189 Gearien, J. E., 173 Geiger, P. J., 133, 141 Geismann, C., 221 Gelfand, L. S., 13 Gence, G., 42, 83 Gennis, R. B., 129 Geoffrey, M., 249 Gerdil, R.,74 Gerlach, R.,227 Gerlt, J. A., 98, 113, 166, 173, 174, 175, 176, 256 Germain, G., 125 German, N. M., 261 Gerster, G., 64, 77 Gesing, E. R., 219 Giamalva, D., 228 Gibbs, D. E., 243 Gibson, J. A., 243 Gigot, D., 135 Gilbert, H. R., 169 Gilbert, J. C., 228 Gilchrist, M., 143 Gilchrist. T. L.. 85 Gilham, P. T., 194 Gillam, S., 201 Gillen, M. F., 171, 191 Gillesoie. P.. 142 Gilya;ov; V: A., 249 Gilyazov, M. M., 246 Gimzewski, J. K., 253 Ginet, L., 249 Giongo, G. M., 10 Giovagnotti, M. L. L., 261 Girard, Y.,214 Gleason, J. G., 215 Glimcher, M. J., 139 Gloede, J., 40, 87, 241 Glowka, M. L., 64, 255, 256 Gloyna, D., 252 Glukhikh, V. I., 10, 60, 101 Godovikov, N. N., 255 Goebel, D. W., 81 Goetze, T., 248 Gold, J. M., 226 Goldfield, E. M., 110 Goldmann, S., 227 Goldschmidt, J. M. E., 244 Gol’dshtein, I. P., 260 Gololobov, Yu. G., 16, 41, 49, 58, 97, 98, 99, 105, 117 Golubinskii, A. V., 257 Golubski, Z. E., 106 Gompper, R., 13, 207 Gonbeau, D., 253 Goncalves, H., 39 Gonzalez, L., 64 Gopal, H., 2 Gordeev, V. K., 68 Gorenstein, D. G., 110, 112, 114, 143, 247 Gorgues, A., 214 Goryunov, E. I., 244 Gossauer, A., 224

Author Index Goswami, B. B., 188 Goto, G., 215 Cough, G. R.,194 Gounaris, A . D., 261 Gourisse, D., 75 Cower, M., 13 Grabley, F. F., 223 Grachev, M. K., 244 Gramstad, T., 256 Granata, A,, 18 Grand, A., 245, 255 Granoth, I., 8, 34. 35, 241, 259 Grapov, A . F., 246 Grathwohl, C., 240 Gray, G. A.. 245 Gray, M . D. M., 110 Grazi, E., 136 Greber, G . , 6 Cree, R.,214 Greene, A. R., 195 Greenleaf, A . L., 141 Gregoire, R . J., 195 Gresser, G., 19, 57 Grieco, P. A., 18, 234 Grjfiths, D. V., 1 2 Griller, D., 21, 253 Grim, S. O., I , 240 Grishina, 0. N., 46 Grobe. J.. 250 Gromova; E. S., 197 Gross, B., 14, 87 Gross, H., 40, 87, 241 Gross. H. J.. 201 Grossmann,’G., 245, 248 Grundwald, M., 75, 251 Gryaznov, P. I., 39 Grynkiewicz, G., 16 Grzejszczak, S., 106, 226 Grzeskowiak, K., 194 Gubaidullin, F. F., 250 Gubaidullin, R. N., 257 Guedj, R., 62 Guilfoyle, T. J., 186 Guillerm, D., 3, 5 5 , 94 Guimaraes, A. C., 255 Guimon, C., 30 Guindon, Y.,214 Gulyaev, N. N., 176 Gumport, R. I., 199 Gupalo, A . P., 117 Gupta R. C. 200 Gupta, R. K., 179 Gurarii, L. I., 257 Gur’yanova, E. N., 252, 280 Guschlbauer, W., 167 Gusev, A. I., 254 Guseva, F. F., 117 Gutekunst, G., 57 Gutterson, N. I., 113, 173 Guy, A., 191 Haake, P., 143 Haas, C. K., 1 Habermann, D., 7,53 Haenssgen, D., 2 Haertlt, T., 167 Hager, V., 137 Hahn, C-S., 82 Halazy, S., 55 Haley, B. E., 189 Hall, C. D., 32, 77 Hall, C. R., 96, 125

Hall, L. D., 244 Hall, N., 79, 105 Halstenberg, M., 19, 33, 58 Haltiwanger, R . C., 254 Hamada, Y.,1 1 1 Hamana, H., 31 Hamer, N. K., 143 Hamill, B. J., 228 Hammerstrom, S., 215 Hampton, A., 188 Hanada, Y.,186 Hanafusa, F., 126 Hanna, H. K., 258 Hansen, B., 142 Hansson, E., 137 Harding, A., 5 , 254 Hareda. H., 121 Harger, M. J. P., 126 Hargis, J. H., 46, 243, 256 Hargrave, K. D., 254 Harpp, D. N., 18, 85 Harris, C . J., 234 Harris, R. K., 6, 241 Harrison, C. R., 21 I Harrison, J. M., 113 Hartley, F. R., 64 Hartstock, F., 21 Harusawa, S., 1 1 1 Hashimoto, M., 133, 134 Hasslberger, G., 254 Hassner. A . , 28, 40 Hata, T., 82. 97, 129, 154, 164,.193, 225 Haubrich, G., 21, 209 Hauske, J. R., 235 Hawkinson, S. W., 256 Hay, R. S., 250 Hayashi, A., 261 Hayashi, M., 1 1 1, 200, 235 Hayashi, T., 6, 8, 10 Heathcliffe, G. R., 195 Heathcock, C. H., 236 Heau, L., 110 Hegenauer, J., 138 Heide, W., 31 Heindel. N. D., 18 Heldt, H. W., 261 Helgstrand, E., 138 Helliwell, J. R., 128 Hellwinkel, D., 32 Hellyer, J. M., 143 Helmreich, E. J. M., 130 Hemmi, K., 133, 134 Hemming, B. C., 261 Hempel, H. V., 106 Henderson, G. B., 188 Henderson, W. A., 6 Henjes, H., 255 Henning, H. G., 252 Henning, R., 230 Henrick, K., 76 Hercouet, A., 219 Hess, H., 32 Heydt, A., 70, 121, 232 Hieter, P. A,, 201 Hill, W. E., 4 Himes, V. L., 99, 256 Hinchcliffe, A., 248 Hinton, D. M., 199 Hirade, T., 75 Hirai, K.,200 Hirschberg, C. B., 130 Ho, Y-K., 198

Author Index Hoa Tran Thi, Q., 170 Hobbs, J., 199 Hobbs, J. B., 165 Hock. A.. 154 Hodge, P:, 211 Hodges, R. V., 253 Hoehne. S.. 255 Holderich, 'W., 7 Hoerl, M., 130 Hoffman, R. W., 227 Hogaboom, G. K., 189 Hoge, R., 255 Hohorst, H. J., 99 Holl, P., 58, 243 Yolme, G., 214 1jolmes, K. R., 32, 256 1-Joly, A., 177 I-Jonda, S., 97 1l o n g , C. I., 171 Iqoogenraad, N. J., 135 Idoornaert, C., 6 1jo p p e, J., 175 Iqorigane, A., 135 Iqoriguchi, M., 135 Idorii, H., 28, 253 1dorn, T., 196 -Iorner, L., 2, 27 -Jorning, D. P., 143 -Ioualla. D., 246, 253 doule, F. A., 253 Idountondji, C., 190 doward, J. E., 139 dowells, R. D., 13, 58, 208 qowie, R. A.. 74 Idowlett, G. J., 135 doyano, Y. Y., 112 -Isiung, H. M., 195 -Iu, A., 180, 241 -Iuang, C-H., 2 duang, G-F., 199 duang, L., 132 -Iuang Wong, Y.-H., 128, 129 -Iuber, F., 75, 255 -Iuber, G., 154 dubmann, F. H., 132 dudson, C. W., 5 , 254 -Judson, H. R., 76 -Judson, R. F., 91 -Judson, R. L., 249 quennekens, F. M., 188 dughes, A. N., 29, 71 duahes. M. K.. 75 Hun, W. E., 179, 241 Hullot, P., 26 Humble. E.. 138 Humeres, E:, 143 Hunig, S., 215 Hunneman, D. H., 175, 183 Hunt, R., 258 Huppertz, M., 14 Hursthouse, M. B., 22 Husebye, S., 256 Hussain, W., 1 Hutchins, R. 0.. 90, 96, 254 Hutchinson, D. W., 140, 198 Hutley, B. G., 25, 31, 74 Huttner, G., 19, 33, 52, 58 Hynie, S., 131 Ibragimova, S. D., 257 Ichihara, A., 213 Ignat'ev, V. M., 102, 123, 124

267 Ignat'eva, S. N., 257 litaka, Y., 256 Ikeda, Y., 6 Ikehara, M., 172, 190, 194, 195, 196, 199, 200 Il'ina, 0. M., 110, 260 Il'yasov, A. V., 13, 63, 247, 249, 250 Imai, K., 167 Inamoto, N., 69, 102, 126 Inch, T . D., 96, 1 1 3, 125 Indzhikyan, M. G., 13 Ingleson. D., 109 Ingold, K. U., 21, 253 Inokawa, S., 17, 121. 247 Inornata, K., 164 Inoue, I., 171 Inouye, Y., 13, 208 loannou. P. V.. I3 1 onin, B. I., 47,'88, 102, 103, 123, 124 onov, B. M., 246 ritani. N.. 75 saev, V, L., 119 shii, K., 261 shikawa, N., 37 shizuka, Y., 10 I shmaeva, E. A., 116, 257 slamov, R. G., 253 smagilova, N. M., 52, 63 ssleib, K., 1 1 , 19, 21 I stomin, B. I., 126, 259, 260 takura, K., 195 tokawa, Y., 261 tskova, A. L., 118 vanov, A. B., 75 I vanov. B. E.. 42. 107. 110.. 260 Ivanova, Zh. M., 98, 99 Ives, D. H., 182 lyengar, R., 128 Izmailova, Z. M., 60 I

,

,

Jackson, E. L., 153 Jacob, K., 260 Jacobsen. J. P.. 119 Jacobson; E., 130 Jacobson, R . A., 90, 254, 255. 256 Jacobson, S. E., 7 Jacobus, J., 244 Jacquemotte-Louis, M., I54 Jacques, J., 109 Jaffe, E. K., 182, 184 Jain, M. K., 131 Jalilian, M., 252 James, T. L., 127 Janes, A. B., 12 Jansen, W., 126 Janzen, A. F., 35, 53, 60, 243 Jardin, J., 234 Jarrnan, M., 100, 140, 261 Jastorff, B., 175 Javed, A., 178 Jayaraman, K., 197 Jeanneaux, F., 37 Jencks, W. P., 143 Jenkins, H. D. B., 60 Jenkins, S. E., 128 Jennings, J. R., 32, 77 Jennings, W. B., 46 Jennings, W. E., 243 Jensen, K. G., 119

Jin, G. Yu., 10 Johansson, C. E., 260 Johannsen, G., 7 Johansson, N. G., 138 John, A. M., 5, 254 John, G. R., 13 Johnson, B. F. G., 214 Johnson, D. K., 7, 21 Johnson, E. M., 178 Johnson, L. D., 260 Johnson, T. H., 6, 92 Johnson, W. S., 237 Jolly, W. L., 58 Jonak, J., 173 Jones, A. C., 79 Jones, A. S., 198 Jones, C. E., 138 Jones, R. A., 2, 22 Jones. R . €3.. 127 Jones; S. R.,'97, 127 Jones, S. S., 196 Jones, T. R. B., 258 Jongebloed. H.. 7 Jonxers, F.' L.,' 52, 66, 219, 227 Jordan, M., 27 Jore, D., 2 Jugie, G., 246 Juodka, B., 165 Kabachnik. M. I.. 4. 44. 45. 48, 67, 74, 75,' 244, 249; 254, 255, 259 Kachroo, P. L., 75 Kadvrov. R. A.. 246.' 257 Kagan, H. B., 6, 9 Kaiser, E. T., 143, 185 Kakeya, N., 9 Kakiuchi, N., 199 Kakternieks, P., 39 Kalabina, A. V., 59, 126,252 Kalaritis, P., 171 Kal'chenko, V. I., 96 Kalinin, A. E., 256 Kalinin, E. A., 254, 255 Kalinin, V. N., 257 Kalman, A., 17 Kalman, T. I., 168 Kalyagin, G. A., 251 Kamba, H., 75 Kamiya, T., 133, 134 Kamminga, P. A., 255 Kampe, W., 140 Kaneda, K., 21 Kane-Maguire, L. A. P., 13 Kanno, T., 75 Kanska, M., 1 Kant, R., 75 Kapitanova, N. G . , 253 Kaplan, N. O., 177 Kapmeyer, H., 177 Kappler, F., 188 Kar, K., 143 Karcher, B. A., 90, 256 Kardanov, N. A., 255 Karelov, A. A., 246 Kargin, Yu. M., 24 Karhu, M., 74, 255 Karnalov, R. M., 115 Karolak-Wojciechowska, J., 256 Karpetsky, T. P., 201 Karrenbrock, F., 226

268 Karsch, H. H., 6, 209, 245, 254 Kasai, H., 256 Kashirskaya, I. M., 52, 63 Kasper, C. B., 138 Kassab, R., 189 Kasukhin, L. F., 16, 49 Kataev, E. G., 122 Kato, M., 176, 193 Katritzky, A. R., 98 Kaufman, V. R., 21 Kaufmann, G., 9, 73, 240 Kauffmann, T., 4, 66, 232 Kaushik, M. P., 55 Kauth, H., 24 Kavunenko, A. P., 177 Kawasaki, T., 18, 62, 81, 106, 261 Kawashima, T., 37 Kawaski, T., 18 Kazankova, M. A., 47 Kazitsyna, L. A., 28, 258 Keat, R., 18, 67, 255 Keck, H., 258 Keim, H., 53, 95 Keiter, R. L., 7 Kellerman, D., 143 Kelly, D. R., 234 Kemp, B. E., 139 Kenn, M., 126 Kenner, G. W., 18 Kent, S., 261 Kenyon, G. L., 106, 113, 141, 153 Kerrick, W. G. L., 185 Kerst, F., 144 Ketari, R., 15, 88 Keyser, G. E., 171, 187 Keyser, T., 6 Khan, S. A., 143 Khaskin, B. A., 117 Khatra, B. S., 138 Khayarov, A. I., 122 Khetagurova, S. Sh., 246, 257 Khetrapal, C. L., 243 Khismatullina, L. A., 42 Khlebnikov, V. N., 45 Khmilovskaya, M. I., 117 Khodak, A. A., 249 Khorana, H. G., 132, 133, 195 Khoury, G., 200 Khristov, V. Kh., 123 Khusainova, N. G., 122,124, 257 Kibardin, A. M., 39 Kice, J. L., 22 Kiener, P. A., 127 Ktkot, B. S., 250 Kikuchi, Y., 200 Kikukawa, K,. 21 Kim, S.-H., 171 Kim, T. V., 98, 99 Kimura. J.. 164 Kimura; M., 261 Kinas, R. W., 98, 100, 140, 173, 175, 245 Kinney, Y. E., 261 Kinoshita. M.. 111 Kinzig, C.‘ M.;215 Kirby, A. J., 143 Kirilov, M., 102, 123, 124

Author Index Kirschner, K., 137 Kirveliene, V., 165 Kisselev, L. L., 201 Kita, Y., 18, 62 Kitaev, Yu. P., 253 Kitazume, T., 37 Kiyohara, M., 82 Klatbk, A., 37 Klautke, S., 7 Kleinmann, I., 261 Kieiner, H. J., 108 Klindukhova, T. K., 23 Klose, G., 248 Klose, W.. 238 Kloth; B.,’7 Kluge, A. F., 228 Kluger, R., 1 1 I , 129 KnaDczvk. J. W.. 12 Knauf, -W:, 233 Knedel, M., 260 Knolevech, A. A., 101 Knoll, F., 19, 58 Knoll, L., 224 Knowles, J. R., 97, 127, 182 Knunyants, I. L., 119 Knutson, K., 99 Knuuttila, H., 255 Knuuttila, P., 255 Kobayashi, S., 42 Kobayashi, T., 42 Kobayashi, Y., 31, 118 Kobenko, L. A., 62 Koch, D., 7, 56 Kochergina, L. A., 259 Kochetkova, N. E., 75 Kochi, J. K., 24 Kocienski, P. J., 218 Komives, T., 111 Koster, H., 193 Kottner, J., 6 Koenig, M., 36, 42, 83, 88, ’

92

Kotkgkramer, R. E., 120, 225. 232 Kofold, E. C., 195 Kohli, V., 193 Koizumi, T., 118 Kojj, A., 116 Kojima, M., 121 Kojima, T., 75 Kolbe, W., 64 Kolbina, V. E.. 60, 101 Kolesnik, N. P., 37, 61, 248 Kolesova, V. A., 126, 258 Kollman, P. A., 113 Kolodyazhnyi, 0. I., 19, 20, 22, 48, 88, 105, 206 Kolomiets, A. F., 101 Kolomyitseva, E. N., 200 Kolosov, M. N., 192 Komendantov, M. I . , 23 Komissarova, N. L., 35 Komura, H., 140, 170 Kondo, H., 130, 132 Kondo, K., 171 Konishi, M., 10 Konovalova, I. V., 77, 108, 109 Koppenhoefer, B., 16 Korolova, T. I., 117 Kormachev, V. V., 60, 71, 252 Kornuta, P. P., 62

Koroleva, G. E., 251 Koroteev, M . P., 246 Korpela, T., 242 Korpusov, G. V., 75 Koschatzky, K. H., 233 KosolaDova. I. I.. 60 Kossmehl, G., 207 Kost, D., 243 Kostina. V. G.. 60. 68 Kostroia, S . M . , 104 Kostyanovskii, R . G., 10 Kotlyarevskii, I. L., 121 Kovhcs, J., 17 Kovaleva, T. V., 55 Kow, A., 76 Kowal, R.,258 Koyama, T., 128 Kozarich, J. W., 188 Kozhushko, B. N., 244 Kozlov, E. S., 61, 248 Kozlov, I. A,, 190 Kozlov, N . S., 260 Koz’menko, M. V., 252 Kraemer, R., 30, 39, 83, 89 Krahmer, U., 196 Krakow, J. S., 188 Kramer, P. A., 14 Krapp, W., 32 Krasil’nikova, E. A., 242 Kraszewski, A., 193 Krauser, S. F., 238 Krawczuk. H. W. 244 Krebs, E. G., 139 Krebs, G., 138 Krief, A., 55 Krishtal, V. S., 96 Kritzyn, A. M., 186 Kroklina, S. S., 107 Krolevets, A. A,, 101 Krongauz, Yu. O., 118 Krooth, R. S., 140, 170 Kroshefsky, R. D., 90, 243, 247 Kroto, H. W., 20, 46, 252, 253 Kruchinina N. E., 75 Kruczynski, L. J., 35, 53 Kruglov, A. S., 47 Krumdieck, C. L., 141 Krupp, G . ; 201 . Kruse, C. G., 26, 66, 76 Kryukov, L. N., 119 Kryukova, L. Yu., 119 Kubisen, S. J. Jr., 28 Kubo, Y.,116 Kubota, T., 37 Kuchen, W., 109, 125, 244, 258 Kucheruk, L. V., 260 Kudinov, A. R., 47 Kudinova, V. V., 53, 68 Kudo, K., 143 Kudryavtseva, L. A., 110, 241, 260 Kudyakov, N. M., 10, 257 Kuhn, E. S., 155,159 Kukhar,V. P., 15, 17, 19,76, 88 Kukhtin, V. A., 60, 71, 252 Kulpe, S., 74, 255 Kumada, M., 8, 10 Kumadaki, I., 31 Kumamoto, J., 143

Author Index Kurnar, N., 75 Kumar, R., 75 Kume, A., 225 Kunwar, A. C., 243 Kunz, H., 16, 24 Kunze, U., 20 Kuramshin, I. Ya., 260 Kurguzova, A. M., 241 Kurihara, H., 261 Kurtev, K., 2 Kuster, J., 178 Kutova, L. V., 75 Kutschatsky, L., 116, 256 Kutter, J., 109, 244 Kutyrev, A. A., 116 Kutyrev, G. A., 116, 257 Kutzelnigg, W., 243, 257 Kuz’min, M. G., 252 Kuznetsov, V. A., 260 Kuznetsova, L. M., I5 Kuznetsova, N. F., 189 Kuznetsova, 0. S., 52 Kvintovics, P., 243 Kyba, E. P., 5, 254 Kyuntsel, 1. A., 248 Laarhoven, W. H., 130 Labarre, J. F., 256 Labaw, C. S., 26 L’abbk, G., 125 Labbe, J.-P., 189 Lam, K. S., 138 Landt, M., 135 Langdon, S. P., 184 Langer, I., 226 Lapin, A. A., 259 Lapp, R. L., 255 Lappi, D. A., 177 Larner, J., 138 Larsen, K., 5, 254 Larsen, S., 3, 254 Larsson, A., 138 Larue, M., 214 Lattman, M., 24 Latyshev, N. A., 261 Laubach, B., 19, 58 Lauer, M., 9 Laugier, J., 245 Laurenco, C., 9, 73 Laurenson, G. S., 46 Lavielle, G., 232 Lavrent’ev, A. N., 260 Lavrik, 0. I., 189 Lawesson. S. O., 108, 125 Lawlor, J. M., 143 Lazarus, R. A., 112, 135 Lazzaroni, R.,4 Leadbetter, M. G., 141 Lebedev, E. P., 115, 120 Lebedeva, N. Yu., 8, 73,104 Le Bozec, H., 21 Leclerq, M., 109 le coq, A., 214 Le Corre, M., 219 Ledley, G., 199 Lee, C. H., 26 Lee, C.-K., 82 Lee, Y .G., 143 Lee, L.-Y., 244 Lee, T. V., 234 Lefferts, J. L., 1 1 Legin, G. Ya., 96, 245 Legocki, J., 82

269 Lehmann, V., 133 Lehninger, A. L., 139 Leigh, G. J., 1 Leissring, E., 11, 19 LeLong, A. L. M., 260 Le Markchal, P., 131 Lemrnen, P., 1 1 1 Leonard, N. J., 187 Leont’eva, I . V., 48, 242 Leroux, A., 138 Leroux, Y., 12, 32, 78, 207 Lesiak, K.,98, 165, 173, 174, 175, 244, 245 Lesnikowski, 2. J., 98, 244 Letsinger, R. L., 196 Levason, W., 5 Level, M., I3 1 Levin, D. H., 138 Levin, Ya. A., 249, 250 Levy, C. C., 201 Levy, H. M., 159 Lewin, M., 21 Lewis, J . , 214 Lex. J.. 236 Lhotak, H., 4 Li, Y. S., 252 Liauw, W. G., 244 Libson. K.. 136 Liebecq, C:, 154 Lilley, R. M., 261 Lin, T., 71 Lin, T.-W., 255 Lindberg, B. K., 17 Lindner, .E., 95, 255 Liorancaite, L., 165 Liorber, B. G., 250 LiDatova. I. P.. 251 Lipkin, D., 154 Little, R. D., 235 Littlefield, L. B., 241 Llewellvn. D. R.. 143 Lobandv,’D. I., 44 Lobanov, 0. P., 26 Loginova, G. M., 41, 123 Logunov, A. P., 258 Lohman, K., 154 Lokhotskaya, L. A., 60 Lomakina, T. S.,15 London, I. M., 138 Lopez, L., 36 Lopresti, R. J., 238 Lorenz. K., 258 Lowe, C. R., 127 Loew, G., 179, 184, 241 Lowe, P. N., 190 Lowenstein, J. M., 154 Lo-Yin, W., 261 Luber, J., 251, 254 Lucken, G. A. C., 249 Ludlum, D. B., 198 Lukashev, N. V., 68 Lundell, J., 242 Lutsenko. I. F..~.45. 47. 49. 53, 68 Lux, D., 32, 255 Luxon. B. A.. 110. 112 Lysov,’Yu. P:, 172 Lythgoe, B., 218 Lyuts, A. E., 258 Maak, N., 221 Maas, G., 255

McAuliffe, C. A., 4, 5 McCaffrey, D. J. A., I , 64 Maccagnani, G., 223 McCoy, M. I. M., 199 McCullough, F. P., 5 McDonald, W. S., 2 MacDougall, J. J . , 30 McEwen, W. E., 12 McFarlane, W., 246 Machida, H., 171 McKee, M. L., 24 McKenna, C. E., 120 McLafferty, F. W., 97, 127 McMurry, J. E., 238 McPhail, A. T., 254 McPhaul, M. J . , 5, 254 McQuillan, G. P.,74 Madan, 0. P., 142 Magdesieva, N. N., 12 Magnane, R., 55 Magnus, P., 119 Mahle, C., 139 Mahler, W., 248 Maier, E., 260 Maier, L.. 107 Maillet, R.,9, 68 Majoral, J-P., 30, 39, 83, 89 Makarova. N. A.. 258 Makinen, E., 242’ Malakhova, 1. G., 67, 259 Malevannaya, R. A., 67 Malhotra, K. C., 75 Malinowski, R.,82 Malkov, Yu. K., 47 Malrieu, J . P., 207 Mammarella, R. E., 28 Mamrack, M. D., 138 Mandel’baum, Ya. A , , 1 I8 Mandl, J. R., 224 Manning, D. L., 26 Manohar, H., 256 Marat, R. K., 60, 243 Marchetti, V., 23 Marecek, J. F., 12, 96, 131, 142, 155, 158, 159 Marfat. A,. 215 Mark, E., 16 Markham, A. F., 190, 195 Markham, R., 2, 154 Markl. G.. 10. 71 Markovskii, L. N., 22, 37, 58, 62, 68, 69, 88, 96 Markowska, A., 97, 117 Marlier, J. F., 167 Marquarding, D., 142 Marsh, F. J., 1 1 3 Marston. A., 18 Martell, A. E., 130 Martelli, J., 214 Martin, J. C., 34, 35, 241, 259 Martin, M. N., 260 Martinez, G. R., 22, 208 Marton, A. F., 11 Martynyuk, A. P., 26 Maryanoff, B. E., 90, 96, 254 Marvanoff. C. A..~.90. 96 Masaki, M., 9 Mashkova, T.D., 201 Mashlyakovskii, L. N., 102 Masson. P.. 214 Mastalerz, P., 80. 107 Mastyukov, V. S., 251

Author Index Mastryukova, T. A., 48, 242, 254 Masui, M., 24, 75, 79, 105 Matevosvan. G. L.. 118. 121. 260 Mathey, F., 9, 29, 30, 3 1, 68, 71, 73, 95, 105, 232, 240, 243. 254 Mathis, R.,25 Matrosov, E. 1.. 4 Matsuda, T., 21 Matsukage, A., 186 Matsukawa, T., 164 Matsumoto, A., 194 Matsumoto, H., 8 Matsumoto, T., 135 Matsushita, Y., 121 Matsuura, F., 261 Matteucci, M. D., 195 Matyushicheva, R. M., 121 Mauro, D., 261 Marecek, J. F., 144 Mayasoedov, B. F., 75 Mayerle, J. J.. 30 Maynard, J. A,, 153 Mazanec, T. J., 7 Mazerolles, P., 20, 57 Mazhar-ul-Haque, 254 Mazo, A. M., 201 Mazurova, L. A., 176 Mazzanti, G., 223 Medved. T. Y., 74, 75 Meek, D. W., 7 Megera, I. V., 24 Meggendorfer, G., 11I Mehdi, S., 98, 166 Mehrotra, G., 75 Mehta, J. R., 198 Mel’nichuk, E. A., 45 Melnick, B. P., 196 Mel’nikov, N. N., 246 Menchen, S. M., 118 Mercier, F., 9, 95, 232 Mercier, R.,71 Merrem, H. J., 247 Mertes, M. P., 167, 168, 171 Mesch, K. A., 241 Messerschmidt, A., 116, 256 Messina, G., 62 Messmer, A., 17 Mestres, R.,260 Mesyats, S. P., 67 Meszaros, Z., 11 1 Metelev, V. G., 200 Metzger, J., 12 Metzler, D. E., 130 Meunier, P., 29 Meyer, B., 245 Meyer, D., 6 Meyer, H., 19 Meyer, R. B., Jr., 175, 176 Meyers, A. I., 230 Meyers, R. F., 237 Meyerson, S., 142, 155, 159 Mhala, M. M., 143 Michaelis, K., 233 Michalska, M., 245 Michalski, J., 43, 60, 85, 86, 97, 98, 241, 245 Michman, M., 21 Michnieweicz, J., 195 Middlemas, E. D., 8, 48, 73 Middleton, D. L.,18 -

,

Mighell, A. D., 99, 256 Mikhailova, N. V., 77, 109 Mikhailova, T. S., 123, 124 Mikhalin, N. V., 121 Mikolajczyk. M., 3, 27, 93, 106, 226, 244, 257 Mildvan, A. S., 179 Milgrom, Y. M., 190 Miller, D. L., 157 Miller, G., 224 Miller, J. A., 52 Miller, J. M., 258 Miller, J. P., 175 Miller, K. F., 22 Miller, P. S., 197 Miller, R. L., 169 Miller, S. I., 27 Miller, W. H., 169 Minkin, V. S., 60, 242 Mironov, V. F., 120 Mishenina, G. F., 165 Mioskowski, C., 215 Mislow, K., 243 Misyura, A. V., 22 Mitchell, J. D., 1, 240 Mitchell, J. S ., 140 Mitrasov, Yu. N., 60 Mitschler, A., 29, 254 Mitsunobu, O., 164 Miura, K., 177 Miyake, N., 8 Miyake, T., 194, 199 Miyazawa, T., 256 Miyashita, S., 37 Miyoshi, K.-I.. 195 Mizhiritskii, M. D., 115, 120 Mlotkowska, B., 97 Modro, T. A., 242. 244 Moedritzer, K., 71, 255 Moers, F. G., 75 Mohan, M. S., 154 Mohiuddin, R., 8 Mohri, A., 37 Mohri, T., 164 Moiseeva, 0. A., 75 Mokeeva, V. A,, 248 Molenda, R. P., I , 240 Molinari, H., 4, 24 Molko, D., 191 Moll, H., 155 Monakhova, T. G., 108 Monastyrskaya, G. S., 200 Mont, D., 126 Montag, R. A., 253 Montanari, F., 24 Montemayor, R. G., 47 Moretti, M. D., 62 Morgan, J. R., 246 Mori, T., 28, 253 Morin, F. G., 245 Morita, N., 27 Morita, T., 62 Morita, Y., 4 Morito, N., 97 Morozova. 1. D.. 242 Morr, M.,’175 Morton, D. R.,Jr., 235, 237 Morton, J. R.,20 Morton. S.. 7 Mosbach, A., 261 Mosbach, K., 127 Moshkina, T. M., 108 Moskva, V. V., 122, 251 ’

Motoyoshiya, J., 105,231 Moulton. C. J., 1 1 Muchowski, J. M., 17 Muhlradt, P. F., 133 Mueller, H., 250 Mueller, J., 245 Mueller, U., 254 Muskens, P. J. W. M., 75 Mukai, J.-I., 186 Mukai, K., 110 Mukaiyama, T., 97 Mukhacheva, 0. A,, 70 Mukhitova, F. K., 122 Mukhtarov, A., Sh., 249,250 Mukmenev, E. T., 256, 257 Muller, G., 224 Muller, I., 222 Mulzer, J., 16 Mumzhieva, N. G . , 246 Mundt, O., 19, 57, 254 Munoz, A., 36, 37, 42, 83, 88, 92 Murakami, Y., 130 Murao. S., 186 Muresan. V., 1 11, 244 Murray, S. G., 5 Murrer, B. A., 6 Musierowicz, S., 227, 244 Musin, R. Z., 258 Mutzler, J., 260 Naae, D. G., 71, 255 Naaktgeboren, A. J., 11 Nace, G., 138 Naemura, K., 219 Nagel, U., 4 Nagao, K., 199 Naguib, Y. M. A., 26, 219 Nagura, T., 171 Nakagawa, E., 199 Nakahara, S.,219 Nakai, S., 24, 79, 105 Nakajima, M., 225 Nakamura, E., 211 Nakamura, Y., 4 Nakanishi, K., 140, 170 Nakanishi. Y.. 130 Nakayama, C:, 171 Nakazaki, M., 219 Narang, S. A., 195 Narang, S. C., 17 Nardi, N.,5 Nasakkala, M., 255 Naumov. V. A., 46, 256 Navech, J., 30, 39, 83, 89, 247 Nayar, M. S., 261 Nazmutdinov, R.Ya., 35,259 Nechaev, A., 171 Neeser, J.-R., 64 Nefed’ev, E. S., 60, 242 Negrebetskii, V. V., 243, 246, 252 Neilson, R. H., 81 Neilson, T., 195 Neininen, K., 255 Nelson, J. H., 30 Nelson, S. M., 209 Nene, D. M., 232 Nesterenko, D. P., 99 Nesterova, L. I., 58 Nesterova, 0. M., 250 Netzel, E., 138

Author Index Neugebauer, D., 6, 52, 209, 254

Nevinskv. G. A.. 189 Nevzor&va, 0. L., 242 Newton. C. R.. 195 Newton; M. G : , 256 Newton, P. F., 65, 228, 229 Newton, R. F., 234 N’gando M’pondo, T., 30,39 Nguyen Huang Phuong, 110 Nguyen Thanh Thuong, 110, 191

Nicholas, K. M., 22 Nichols, S., 246 Nicholson, N . H., 125 Nichugina, N. V., 259 Nickisch, K., 238 Nicolaous, K. C., 212 Niecke, E., 89 Niedzwiecki, S., 5, 254 Nief, F., 31, 73 Niemineh, K., 74 Niewiarowski, W., 166 Nifmt’ev, E. E., 80, 96, 107. 244, 245, 246, 255

Nigametzyanov, R. T., 116 Niitsu, M., 75 Nikitin, E. V., 24 Nikohov, G. N., 10 Nikolaeva, V. G., 11 Nilson, J. H., 201 Nilsson, T., 137 Nishjda, S., 261 Nishikawa, S., 199 Nishiniuri. S.. 256 Nishino, T., 186 Niven, I. E., 4 Nixon, J. F., 20, 46, 246, 252. 253

Noeth, H., 246 Nolte, R. J. M., 1 1 Nomoto, T., 193 Nomura, T., 132 Norman, A. D., 58, 254 Normukhamedova, L. V., 55 Norris, K. E., 195 Norton, M. C., 2 Norval, E. M., 241 Nowak, R.,188 Novikova, N. K., 108 Novikova, Z. S., 45, 49, 53 Nowakowski, M., 142 Nowell, I. W., 12, 25, 74 Nowicki, T., 117 Nuck, R.,207 Nunn, M. J., 52 Nuretdinov. I. A.. 55. 109. 117, 252, ’253

Nurgalieva, A. A., 116 Nurtdinov, S. Kh., 51 ,52,63 Nussbaum, S., 21 Nuzzo. R. G.. 10 Nyburk, S. C.’, 21 Oades, A. C., 25, 74 Oakley, R. T., 254 Oberhammer, H., 60, 257 O’Brien, T. A., 129 Ochsler, B., 9 Odintsov, B. M., 250 Odom, J. D., 250 O’Donnell, J. P., 189 dberg, B., 138

27 1 Oehme, H., 1 1 , 19 fihler, E., 23 Ofitserov, E. N., 115, 120, 247

Ogasawara, M., 186 Ogata, I . , 6 Ogata, T., 17, 121, 247 Ogawa, S., 127 Ogilvie, K. K., 171, 191, 193, 194

Ogura, K., 128 Ohashi. 0..20 Ohbe, Y., 21 Ohmori, H., 24, 79, 105, 194 Ohnesorge, A., 260 Ohno. M.. 196 Ohsawa, A., 31 Ohshiro, Y., 105, 231 Ohtsuka, E., 190, 194, 195, 196, 199, 200

Ojima, I., 10 Okamoto, H., 132 Okamoto, Y., 62 Okazaki, H., 144 Okruszek, A., 177 Okruszek, O., 92 Okuda, S., 130 Olah, G. A., 17 Oldham, K. G., 143 Olejnik, J., 97 Oleksyszyn, J., 80, 107 Olson, M. 0. J., 138 Olszewski, N., 186 Omelanczuk, J., 3, 27, 93, 244

Ondetti, M. A., 134 Ono, K., 186 Ono, N., 116 Onur, G., 188 Onys’ko, P. P., 105 Orama, O., 74, 224, 255 O’Regan, C. B., 119 Orgel, L. E., 166 Orlich-Krezel, I., 245 Orton, W. L., 241 Oshie, K., 196 Osman, F. H., 246 Osbirk, A., 119 Oskotskii, E. L., 47 Osowska, K., 119 Osuka, A., 55 Otvos, J. D., 127 Otvos, L., 188 Ouali, M. S., 77 Ovakimyan, M. Zh., 13 Ovchinnikov, V. V., 120, 259 Pak, V. D., 260 Pakulski, M., 43, 60, 85, 86, 24 1 Paliichuk, Yu. A., 244 Palm, J., 236 Pande, P. C., 15 Pankiewicz, K., 100, 140 Panov, A. M., 252 Pantaleo. N. S., 256 Papp, S.,’ 243 Parakin, 0. V., 24 Parish. R. V.. 4 Park, J. S., 168 Park, K. T., 82 Parlina, S. I., 244 Parry, R. W., 47

Parthasarathy, R., 256 Pascard, C., 21 Paskucz, L., 242 Patel, K. R., 133 Patlina, S. I., 80, 107 Patsanovskii, I. I . , 257 Pattenden, G., 236 Patterson, L. K., 21, 253 Patterson, P. L., 260 Paul, C., 137 Paulsen, H., 245 Paulus, E. F., 71 Pavel, G. V., 104 Pavia, M. R., 212 Pavlenkov, N. G., 17, 76 Pavlov, G. P., 252 Payne, N. C., 4 Pearson, M. J., 211 Pedersen, B. S., 108 Pedersen, G. B., 119 Pedrini, P., 223 Penney, C. C., 113, 173, 193 Penninckx, M. 135 Pensionerova, G. A., 60, 101 Perales, A., 256 Perekalin, V. V., 106, 120 Perks, M., 209 Perlikowska, W., 3, 93 Petasis, N. A., 212 Peter, G., 99 Petersen, D. J., 66 Peterson, J., 255 Peterson, M. R.,244 Petrillo, E. W., Jr., 80, 134 Petrov, A. A.,47,49, 88, 102, 103, 123, 124

Petrov, E. S., 67, 259 Petrov, K . A., 8, 67, 73, 104, 108, 122, 259

Petrov, S. I., 28, 258 Petrovskii, P. V., 44, 48, 101 Pfister-Guillouzo, G., 30, 253

Pfleiderer, W., 173, 194, 196 Phillips, G. N., Jr., 141 Phillips, S., 251 Phisithkul, S., 71 Piccinelli, P., 223 Pichat, L., 175 Picker, D., 188 Piers, E., 213, 231 Pieronczyk, W., 6, 8, 92 Pierrat, A., 2 Pietrusiewicz, K. M., 64, 255 Pike, D. C., 129 Pillai, R. P., 185 Pincock, R. E., 112 Pinter, I., 17 Platonov, A. Yu., 3 Platz, H., 233 Plaut. G. W. E.. 128 Pliura, D. H., 182 Poels, E. K., 26, 66, 76 Pohl. S.. 30. 88. 254 Pol, A.,’ 130 ’ Polezhaeva, N. A., 12, 17,41 Polikarpov, Yu. M., 75 Pollack, S. M., 153 Polumbrik, 0.M.,22 Polyanskaya, T. M., 254 Pon, R. T., 193 Ponder, J. W., 234 Ponomarchuk, M. P., 49

272

Author Index

'onsford, R. J., 21 1 'onti, P. P., 23, 206 Donticello, G. S., 15 I3opescu, R., 1 1 I , 242, 259 1'orotikova, V. A., 168 'orter, J. W., 128 'ortis, A . R., 261 'orushnik, M. I., 24 'oshidayev, V. M., 259 'ottage, C., 125 'otter, B. V. L., 179 'otvin, B. W., 140, 170 'ouet, M. J., 206, 246 'oulin, J . C., 6 'ouzard, G., 240 'ovalotskii, M. I., 61, 248 I'overenny, A. M., 200 1'ozhidaev, V. M., 13 1'raefcke, K., 21 1'rasher, D. C., 182 1'redvoditelev, D. A., 244 1'reobrazhenskaya, M. N., 165, 250 1'reston, K. F., 20, 246 1'retzer, D. K., 6 1'reut, H., 75 1'rice. R.. 79 Priesner,'C., 23 Pris, B., 154 Prishchenko, A . A . , 45,49,53 Prokof'ev. A. 1.. 250 Prokof'eva, T. I:, 35, 250 Proll, T., 125 Promonenkov, V. K., 117 Prue, R., 105 Prusoff, W. H., 164 Pudovik, A. N., 13, 24, 35, 38, 39, 41, 45, 77, 96, 108, 109, 110, 115, 116, 120, 121, 122, 123, 124, 242, 257, 259, 260 Pudovik, M. A., 38 Puettmann, M., 90, 246 Ouemeneur. F.. 12 Quell, G . , 28 Quici, S., 24 Quin, L. D., 1, 8, 48, 73, 241 Ouiocho. F. A.. 141 Quirk, J.' M., 21 .

I

Rabinovich, S. P., 121 Rabinovitz, M., 236 Rachon, J., 107 Radionova, N. P., 200 Radke, W., 6 Rae, A. D., 255 Raevskii, 0. A., 246 Raffaelli, A., 4 Raganathan, S., 77 Ragnarsson, V., 138 Rainier, S., 131 Raivio, K. O., 136 Ramirez, A., 260 Ramirez, F., 96, 112, 131, 142, 143, 144, 155, 158, 159 Randerath, K., 200 Ranganathan, D., 77, 106 Ranganathan, S., 106 Rangarajan, G., 6, 92 Rankin, D. W. H., 46, 209, 243,257

Rao, C. B., 77, 106 Rapoport, H., 235 Rastall, M. H., 26, 219 Rathgeber, G . , 189 Ratovskii, G. V., 59, 60, 251, 252 Ratts, K. W., 207 Rau, A., 255 Rausch, M. D., 258 Raushel, F. M., 185 Ray, G., 119 Raza, Z., 171 Razumov, A . I., I I , 70, 122, 242, 250 Razzaque, A . , 186 Reddy, G. S., 244 Redmore, D., 248 Rees, C. W., 8 5 Reese, C. B., 191, 193, 196 Reetz, K. P., 241 Reeves, P. C., 24 Regen, S. L., 24 Regitz, M., 70, 121, 222, 232 Remizov, A. B., 251 Remy, P., 190 Renneboog, R. M., 26, 219 Rensing, A,, 4 Ressner, J. M., I Reuschenbach, G., 7, 56 Reynolds, D. P., 234 Reynolds, G. A., 224 Ribola, D., 2 Richard, J. P., 182, 183 Rjeck, H. P., 227 Rieke, E., 127 Riesel, L., 244 Riess. J. G.. 37 Rifting, F., 197 Rilling, H. C., 128 Rios-Mercadillo, V. M., 132 Ritmeister. J. A.. 60 Riiers, G. T., 226 Rizkalla, E. N.,.251 Rizpolozhenskii, R. I., 251 Roach, P. J., 138 Robenko. L. A., 69 Robert, A., 206 Robert, J. B., 245, 247, 255 Robert. P.. 21 Roberts, B. P., 248, 249, 250 Roberts, C. M., 133, 141 Roberts, M. R., 230 Roberts, N. K., 5 Roberts, P. M., 211 Roberts, S. M., 234 Robillard, G. T., 138 Robins, R. K., 175, 176 Roboz, J., 258, 261 Rockerbie, R. A., 261 Roder, T., 233 Rodewald. G.. 1 1 Roschenthaler, G. V., 37, 39 Rosel, P., 22, 233 Roeskv. H. W.. 32. 48. 256 ' Roessfer. F.. 224 Rogers, W. O., 98, 166 Roget, A., 191 Rokach. R.. 214 Roland,' D. 'M., 230 Romanenko, E. A., 248 Romanenko, V. D., 5 8 , 62, 68,69, 88 '

Romanov, G. V., 13, 24, 35, 45, 110, 259 Romm, I. P. 252 Roossien, F. F., 138 Rose, E., 261 Rose, I . A., 136 Rosemeyer, H., 177 Rosner, M. R., 132, 133 Rosowky, A., 171 Ross, A., 201 Ross, B., 241 Rossomando, E. F., 184 Roth, K., 32,210,216,256 Rottman, F., 201 Rousch, W. R., 226 Rowell, R., 114, 247 Rowley, G. L., 141 Rozanel'skaya, N. A., 243 Rozantsev, E. G., 168 Rozinov, V. G., 60, 101 Ruban, A . V., 88 Rubin, J. R., I29 Rudolph, G., 19 Rudomino, M. V., 259 Ruediger, E. H., 213 Rukachaisirikul, T., 7 1 Ruppert, I., 19, 58 Ryabchenko, S. N., 261 Ryaboi, V. M., 252 Rybakov, V. T., 255 Rychlewski, J., 75 Ryl'tsev, E. V., 251 Saalbaum, H., 23 Saalfrank, R. W., 223 Sabo, E. F., 134 Sabfi, S. S., 83 Sagi, J., 188 Saegusa, T., 42 Saenger, W., 183 Sagina, E. I . , 15, 17, 76 Sahai, R., 15 Saint-Roch, B., 20 Saito, A., 128 Saito, S., 4 Sakaguchi, K., 200 Sakamoto, Y., 193 Sakamura, S., 213 Sakurai. H.. 62 Salakhutdinov, R. A., 47,51, 52, 63 Salaun. J.. 218 Sallis, J. D.,140 Saltman, P., 138 Salvadori, P., 4 Samaan, S., 27, 246 Samarina, 0. A., 257 Samartseva, S. A., 251 Samitov, Yu. Yu., 243 Samsel, E. G., 18 Samuel, O., 9 Samuelsson, B., 15, 21 5 Samukov, V. V., 165 Sanchez, M., 253 Sandhu. R. S.. 75 Sandmeier, D.', 207, 221 Sanemori, H., 261 Saneyoshi, M., 171, 177 Sano. K.. 21 Santi; D.'V., 167, 261 Sarai, K., 261 Sasak, W., 261 Sasavage, N. L.,201

Author Index Sass, S., 258 Sasson, Y., 17 Satge, J., 20, 57 Sathe, G., 178 Sathyanarayana, B. K., 184 Sato, N., 55 Sato, T., 99 Satterthwait, A. C., 132, 153 Sau, A. C., 32, 256 Sauerbrey, K., 39 Savignac, P., 104, 108 Savran, V. I., 51, 63 Saucy, G., 238 Sawai, H., 196 Sayo, N., 84, 86, 97 Scaiano, J. C.. 21 Scarafile, C., 21 1 Schafer, G., I88 Schiifer, H.-J., 189, 226 SchalTer, J . R., 231 Schaumann, E., 223 Schemer, K., 38, 245, 250 Scheller, D., 64, 245 Scherer, 0. J., 90, 246 Scherm, H. P., 209, 224 Scheurich, P., 189 Scheutzow, D., 215 Schifman, A. L., 193 Schlageck, J. G., 187 Schlessinger, R. H., 230 Schlimme, E., 188 Schlosser, M., 217, 237 Schniid, G., 221 Schmidbaur, H., 22, 55, 58, 209, 224, 243, 254, 255 Schmidhauser, J., 120 Schniidpeter, A., 30, 32, 40, 43, 47, 98, 251, 254, 256 Schmidt, C. L., 168 Schmidt, H., I I , 19 Schmidt, O., 126 Schmidt, P., 16 Schmutzler, R.,37, 39,256 Schnackerz, K. D., 130 Schneider, P. W., 154, 1 5 5 Schiips, R.,64 Schoerner, Ch., 10 Schofield, C. N., 260 Schomburg, D., 32, 39, 182, 256 Schore, N. E., 4, 7 Schramm, V. L., 169 Schroeder, H. F., 245 Schubert, P. F., 254 Schubert, V., 6, 22, 74, 209, 224, 254, 255 Schulman, M., 261 Schulten, H. R.,258 Schulz, P. C., 259, 260 Schumann, H., I1 Schurig, V., 16 Schwarz, R.. I l l Schwarz, W., 32 Schwertfeger, G., 260 Secor, H. V., 99, 256 Sedgwick, R. D., 5 Seegmiller, J. E., 136 Seel, F., 53, 95 Seela, F., 170, 177 Seelig, A., 257 Seelig, J., 257 Segal, 1. S., 38 SegalI, Y.,34, 259

273 Seib, P. A., 261 Seidel, I., 74, 255 Seif, I., 200 Seifert, G., 245 Seip, R., 46, 257 Seitz. S. P., 212 Sekiguchi, M., 24 Sekine, M., 82, 129, 154, 164, 225 Sekine, T., 75 Selsing, E., 199 Semenii, V. Ya., 251 Semin, Yu. A., 200 Serdijn, J., 195 Sergienko, L. M., 59, 60, 252 Seto, S., 128 Severin, E. S., 176 Severtsova, I. V., 192 Seyden-Penne, J., 206, 246 Seyerl, J. V., 33 Seyferth, D., 2, 28 Shabarova, 2. A., 197, 200 Shagidullin, R. R., 116, 251, 252, 257 Shah, D. P., 1 Shaidulin, S. A., 46, 256 Shakir, K., 75 Shakirov, I. Kh., 116, 257 Shaposhnikov, I . G., 248 Sharapov, V. A., 254 Sharma, 0. K., I88 Sharp, T. R., 136 Shatenshtein, A. I., 67, 259 Shaw, B. L., 2, 1 I Shaw, R. A., 100, 247 Shaw, W.-C., 236 Shchelkunova, M. A., 70 Shcherbakova, G. I., 126 Shcherbakova, E. S., 260 Shchukareva, T. M., 47 Shchukin, V. A., 104 She, H. S., 137 Shekhade, A. M., 102, 123 Sheldrick, W. S., 7, 32, 39, 47,48, 256 Sheppard, R. C., 195 Shermolovich, Yu. G., 22, 37 Sheu, K.-F. R., 183 Shevchuk, M. I., 24 Shiau, W.-I., 12 Shibata, T., 196 Shida, T., 172 Shigetomi, Y., 75 Shigimatsu, T., 75 Shih, Y.-E., 99 Shikhaliev, Sh. M., 10 Shima, I., 102 Shimizu, K., 230 Shimoii. K.. 235 Shin, C : , 8 2 Shinya, S., 13, 58, 208 Shiori. T.. I 1 1 Shivaev, V. I., 260 Shively, C. A., 261 Shokol, V. A., 244 Shore, S., 12 Shubina, T. N., 165 Shugar, D., 169, 170 Shukla, K. K., 159 Shulman, R. G., 127, 240 Shurubura, A. K., 251 Shvets, A . A., 75 Shvetsov-Shilovskii, N. I., 99

Sibgatullina, F. G., 109 Sigal, I., 142 Sigel, H., 154 Siller, J., 71 Silver, B. L., 143 Silverman-Jones, C. S., 261 Simalty, M., 27, 31, 73 Simmons, B. P. C., 252 Simmons, N. P. C., 20, 46, 253 Simon, P., 14 Simonnin, M. P.. 206, 246 Simonova, E. V., 260 Simons, R . J., 261 Singh, B., 75 Singh, G., 244 Singh, K., 249, 250 Singh, M., 195 Singh, V., I5 Sinitsa. A. D.. 96 Sisti, M.,126' Sitdikova, T. Sh., 122, 251 Sitton, P. G., 253 Skaric. D.. 171 Skaric; V.,' 171 Skobun, A. S., 103 Skolimowski, J., 27 Skorobogatova, M. S., 249, 250 Skowronska, A., 43, 60, 85, 86, 241 Skowronski, R., 27 Skvortsov, N. K., 103, 123 Sleeper, H. L., 166 Slusarska, E., 126 Small, R. D., Jr., 21 Smirnov, V. D., 200 Smirnov, V. N., 246 Smith, D. J. H., 110, 191 Smith, J. G., 251 Smith, J. H., 12 Smith. K. G.. 5 Smith; L. T.,'184 Smith, M., 201 Smith, P. F., 133 Smith. P. H.. 1 Smith; R. A.; 85, 188 Smithers, R. H., 14, 213 Smrt, J., 131, 173 Snyder, C. E., 2 Sochacki, M., 174 Sochilin, E. G., 260 Soderling, T. R., 138 Soll, D., 200 Sohr, H., 116, 256 Soifer, G. B., 248 Sokola, J. A., I I3 Sokolov, M. P., 250 Solodenko, V. A., 68 Solodova, K. V., 71 Solodovnikov, S. F., 254 Solodovnikov, S. P., 249,250 Sombrock, J., 236 Soretktna, V. E., 121 Sorokina, S. F., 96, 245 Sorokina, T. D., 251 Sotman, S. S., 246, 255 Southgate, R., 21 1 Sowerby, D. B., 256 Spagnolo, P., 41 Speziale, A. J., 207 Spitzmiller, E. R., 80, 134 Sproat, B. S., 179, 241

274

Author Index

Spurgeon, S. L., 128 Srikrishnan, T.. 256 Srivastava, A. K . . 7 5 , 138 Srivastava, T. N., 75 Stalick, J . K., 99, 256 Stam, C. H., 254 Stamm, H., 64, 77 Stan, H. J., 260 Stanislawski, D. A., 240 S t a p h , D. C., 47 Starostina, W. P., 15 Starzewski, K. A. 0.. 253 Stawinski, J., 193 Stec, W. J.. 98, 100, 117, 140, 165. 166. 173. 174.’ 175.‘ 245; 261 Stegmann, H. B., 38, 245. 250 Steinbach, G., 227 Steinbach, J., 244 Steinseifer, F., 4 Stelzer, O., 7, 39 Stemmler, I., 215 Stepanov, B. I., 243, 252 Stepanov, 1. A., 3 Stepanova, A. A., 99 Stepanova, 0. B., 200 Stepanova, T. Ya., 45, I10 Stepashkina, L. V., 251 Stephan, D. W., 4 Stephanson, L. G., 168 Stephen, M. A., 126 Stephenson, G. R.,214 Stepney, R., 234 Sterlin, R. N., 119 Stern, H. J., 140, 170 Stifanova, Yu. P., 52 Stille, J. K., 6 Stingelin, J., 185 Stock, J. A., 186 Stockigt, J., 207 Stollar, B. D., 199 Stone, T. E., 176 Stork, G., 21 I Strepikheev, Yu. A., 126,258 Streusand, B. J., 250 Strong, J. M., 261 Strotmann, H., 188 Struchkov, A. E., 254 Struchkov, Yu. T., 255, 256 Struve, G. E., 141 Stubbe, J., 188 Stults, 9. R.,71, 255 Sturtz, G., 77, 106 Styles, P., 240 Styring, S., 137 Subotkowska. L.. 80. 107 Sugahara, T.,‘234 Sugiura, M., 199 Suhadolnik, R. J., 128, 129 Suk. H.. 261 Sukhorukov, Yu. 1.. 252 Sukumar, S.; 244 Sumida, T., 2 Sun, I. Y.-C., 178 Sun. Y. Y.. 7 Sunamoto.‘J.. 132 Sundar, S.’, 7 Sundberg, M., 255 Sune. L., 195 Sung, W. L.. Suss, T., 233 SusC’T., Sutherland, T. M., 135 Suvorova. G. N., 23 ’

’

Suzuki, H., 55 Suzuki, K., 261 Suzuki. R., 258, 261 Suzuki, S., 130 Svedman, J., 250 Svensmark, O., 141 Sverdlov, E. D., 189, 200 Svoboda, V., 261 Svoren, V. A., 244 Swan, J. M., 153 Swartz, J. E.. 79 Sweenev. D. L.. 173 Sweigait: D. A., 13 Swift, T . J., 130 Szafrah, M., 75, 251 Szamosi. J.. 142 Szego, F., I7 Szemzo, A., 188 Szobota, J . S., 24 Tabony, J., 248 Taborsky, G., 138 Tagawa. J., 69 Tahara, K., 176 Takagi, M., 18. 21 Takaku, H., 167 Takamizawa, A., 121 Takatsuka, Y., 172 Takayamara, E., 251 Takeno, H., 133, 134 Tam, T. F., 235 Tamao, K., 8 Tamborski, C., 2 Tamura, Y., 18, 62 Tanaka, H., 84, 86, 97 Tanaka. K.. 116 Tanaka, M:, 6 Tanaka, S., 200 Tanaka, T., 194, 199 Tanaka. Y 200 Takaku; H.; 193 Taniguchi, S., 28, 253 Tantasheva, F. R., 122 Taqui Khan, M. M., 8, 154 Tarasov, V. V., 75 Tarasova, R. I., 1 1 Tarzivolova, T. A., 250 Tashiro, M., 2 Tashtoush, H. I., 83 Tau, K. D., 7 Tautz, H., 30 Taylor, E. W., 136 Taylor, N. J., 21 Taylor, R . C., 250 Tazaki, M., 18 Tebby, J. C., 12, 247 Teichmann.. H... 24., 119 Teoule, R., 191 Teranishi, S., 21 Terekhova, M. I., 67, 259 Terekhova. T . A.. 261 Terent’eva,’ S. A.,’ 38 Tetas, M., 154 Tew, W. P., 139 Texier-Boullet, F., 81, 226 Thacker, J . D., 217 Thakur, K. P., 60 The, K. I., 243 Theriault, N. Y., 193 Thiem, J., 245 Thierbach, D., 75.255 Thomas, B., 244, 245 Thomas, E. J., 84

..

Thomas, J. D., 253 Thomas, J. W., Jr., 141 Thomas, M. T., 206 Thomen, S., 6 Thompson, M. L., 254 Tilhard, H. J., 66 Tilichenko, M. N., 52, 103, 104 Timokhin, B. V., 60, 61,252 Titova, I . E., 122 Tkachev, V. V., 255 Todd, M. R.,46, 257 Todesco. P. E.. 80 Todesco; P. O.’, 41 Toke$, L., 17 Tolls, E., 7 Tolrnacheva. N. A.. 117 ’ Tomasz, J., 165 tom Dieck, H., 253 Tordo, P., 249 Torgomyan, A. M., 13 Torii, S., 84, 86, 97 Torrence, P. F., 167, 199 Torstenko, V. I., 58, 68, 69 Toth, G., 17 Towers. C.. 29 Toy, A: D.’F., 1 Traber, R. P., 79 Trentham, D. R., 127, 180 Treshchalina. L. V.. 108. 122 ’ Trinquier, G:, 207 ‘ Trjppett, S., 40, 44, 86, 243 Trishin, Yu. G., 49 Trombetta, G., 136 Tronchet, J. M .J., 64 Trost, B. M., 226 Trostyanskaya, 1. G., 47 Trutneva, E. P., 251 Tsarev, S. A., 189 Tsaroom, S., 17 Tsekhanskii, R. S., 252 Tseng, C. K., 85, 241 TseDukh. N. E.. 117 TsiGunin: V. S.,‘ 51, 52, 63 T’so, P. 0. P., 197 Tsou, K. C., 187, 198 Tsou. T. T.. 24 Tsuboil H..’143, 144 Tsui, W.-C’., 1 1 I Tsuji, M., 130 Tsvetkov. E. N.. 4.67. 252 Tsymbal,‘l. F., 251 . Tudrii, @. A., 77 Tukhar, A. A., 259 Tumanskii, B. L., 249 Tundo. P.. 24 Tunitskaya, V. L., 176 Tuong, H. B., 217 Tupchienko, S. K., 117 Turchinskv. M. F.. 189 Turkin, S.-I., 197 . Tuzova, L. L., 46, 256 Tychinskaya, L. Yu., 172 Tyka, R., 107 Tzschach, A., 6, 9, 11, 28 Ubasawa, A., 193 Ubukata, M., 213 Ueda, T. , 177 Uemura, H., 199 Uesell, E. S., 261 Uesugi, S., 172 Uggla, R., 74, 255

275

Author Index Ugi, F., 142 Uni. I.. 1 1 1 Ugurb(l, K., 127, 240 Uhing, E. H., 1 Uhl, W., 19, 57 Uhliu. W.. 6 Uijtcwaaf, A. P., 219 Uhlmann, E., 194 Ujimoto, K., 261 Ullman, B., 176 Ulmer, W., 118 Ulmschneider, K. B., 250 Ulrich, P., 234 Uppenkamp, R., 125 Uriarte, R. J., 7 Usher, D. A., 176 Utley, J . H. P., 28 Vachkov, K., 123, 124 Vaidyanathaswamy, R.,55 Valetdinov, R. K., 10, 13,63, 247 Valitova, L. A., 107 Valitova, V. M., 120, 259 Van Aken, D., 254 Van Allan, J. A., 224 van Boeckel, C. A. A., 131, 191 van Boom, J. H., 131, 191, 194. 195, 196 van de Grampel, J. C., 256 Van de Griend, C. J., 76,246 Van Den Berghe, E. P., 46 van der Drift, C., 130 van der Gen, A., 26, 52, 66, 76, 219, 227 van der Helm, D., 246,255 Van der Kelen, G. P., 46 Van Der Lijn, P., 187 Van Der Mare!, G., 191 Van der Valk, P. D., 208 Vandest, P., 189 van Deursen, P. H., 195 Van Eemoo, M., 55 Van Herk, A., 254 Van Linthoudt, J. P., 46 Van Maanen, J. M. S., 100, 140 van Meerssche, M., 125 Van Wazer, J. R., 240 Varagnat, J., 6 Varlet, J.-M., 108 Varnavskaya, 0. A., 257 Varvoglis, A. G., 143 Vasilev, G., 123 Vasil’ev, V. P., 259 Vasil’eva, I . A., 52, 103 Vasil’eva, M. V., 120 Vasil’eva, T. V., 71 Vas’kovskii, V. E., 261 Vasyanina, L. K., 80, 107, 244Vaultier, M., 77 Vedejs, E., 22, 208 Veech, R. L., 141 Vega, A. J., 248 Veits, Yu. A., 68 Venkataramu. S. D., 246 Venturello, P,; 24 . Verbrugge, P. A., 14 Verkade, J. G., 76,90,91,92, 100. 177. 243. 246. 253. 254; 2 5 6 ,

Vernon, C. A., 143 Veronikin. 0.V.. 101 Verret. R.’c., 133 Verweij, A., 260 Vilkov, L. V., 257 Villafranca, J. J., 185 Villem, Ya. Ya., 253 Vinceus, M., 247 Vink, A. B. J., 194 Vinogradov, L. I., 246 Vinokurov, A. I., 116, 257 Virlichie, J. L., 246 Viswanathan, T. S., 130 Vogel, E., 236 Vogels, G. D., 130 Vogt, W., 260 Voitsekhovskaya, 0. M., 259 Voituriez, L., 261 Vol’eva, V. B., 35 Volodin, I. A., 75 Volz, M., 251 von Criegern, T., 32, 40, 42, 256 von Seyer, J . , 19, 52, 58 Voronkov, M. G., 10, 257 Vors, J.-P., 23, 222 Vos, A., 255 Voskanyan, M. G., 123 Vostrowsky, O., 22, 233 Voznyuk, L. A., 186 Vul’fson, S. G., 46, 257 Vysotskii, V. I., 52, 103, 104 Wachtler, D., 89 Wada, M., 75 Wade, T. N., 62 Wagner, A., 236 Wagner, R.,131 Wagner, R. R., 178 Wakselman, M., 143 Waley, S. G., 127 Walker, B. J., 91, 209, 225 Walker, J. B., 141 Walker, P. E., 12. 25, 74 Walker, R . T., 198 Wallace, L. J.. 188 Walley, E., 60 Wallis, C. J . , 65, 228 Wallmeier, H., 243, 257 Walsh. C.. 130 Walter, W., 125 Walther, B., 64 Waltz, R. H., 260 Wan, W. H. Y., 176 Wang, J.-S., 99 Wang, S.-M., 244 Ward, H., 209 Warren, S., 65, 228 Wartew, G. A., 91 Wasielewski, C., 107 Wasilewski, J., 243 Waszkuc, W. T., 244 Watanabe, K., 177 Watanabe, Y., 97 Watari, F., 251 Waterhouse, I., 218 Watterson. A. C.. Jr.. 238 Wax, R.,233 Webb, M. R.,127, 180 Webb, R. L., 26 Webber. A.. 28 Weber, B., $0, 101, 121 Wedler, F. C., 143 ,

I

Weeks, B., 2 Weerasooriya, U., 228 Weferling, N., 7, 39 Weichmann, H., 9, 28 Weiner, P., 113 Weinmaier, J. H., 30, 32, 254,256 Weinman, S. A., 97, 127 Weiss, E., 55 Weiss, J. V., 256 Weiss, R., 23, 76, 246 Weissman, S. M., 200 Weith, H. L., 194 Welch, V. A., 143 Wellman, G. R.,26 Wells, R. D., 199 Wentworth, R. A. D., 22 Wessely, H. J., 57 West, C. R.,171 Westheimer, F. H., 28, 38, 142, 143, 144, 153, 157, 177 Westwood, N. P. C., 20, 46, 253 Wetzel, D., 261 Weyerstahl, P., 213 Whangbo, M. H., 217 White, D. W., 90, 243, 256 Whiteley, J. M., 168 Whitesides, G. M., 10, 132 Whitham, G. H., 65 228, 229 Whittaker, N., 234 Wieczorek, M., 256 Wiegand, G. H., 18 Wiesenfeld, L., 245 Wiewiorowski, M., 193, 194 Wilburn, J. C., 24 Wild, S. B., 5 Wildbredt, D. A., 89 Wilhelm.. E... 32,, 216, 221, 256 Wilkinson, G., 2, 22 Wilkinson. J . P. T.. 250 Wille-Hazeleger, G:, 194, ~

195

W~lli&ns,E., 18, 234 Williams, F., 249 Williams. G.. 140 Willis, A: C . ; 2 Willson, M., 36, 247 Wilson. D. E.. 140 Wilson: i. F.. ‘12 Wilson; G. W., 26 Wind, M. L., 261 Winer, F. B., 128, 190 Withers. G. P.. 18 Withers; H. P.; Jr., 2 Wodzki. W.. 2 Wohlrab, F.; 167 Wolf, H., 23 Wolf, R., 88 Wolf, U., 13, 207 Wolfe, R. S., 130 Wolff, H., 224 Wolfram, G., 261 Wolin. M. S.. 175 Woltermann,’A., 4 Wong, Y.-H. H., 190 Wong-Ng, W., 21 Wone. P. T. T.. 60 Woo,E. J . , 12 . Woodruff, W. W., 111, 137 Woolfenden, R., 137

276 Worley, S. D., 46, 243 Worms, K. H., 106, 120 Wrackmeyer. B., 246 Wray, V., 7, 133 Wretborn, M., 138 Wright, J. G., 243 Wroblewski, A. E., 91, 100. 227 Wu, R., 195 Wursthorn, K. R.,28 Yafarova, R. L., I I Yagodin, G. A., 75 Yahamoto, Y., 75 Yakiminskaya, N. Sh., 247 Yakobson, G. G., 62 Yakovlev, V. N., 88 Yakutina, 0. E., 252 Yamada, K., 82, 129, 154 Yamada, Y., 110 Yamagata, H., 82 Yamagata, Y., 164 Yamaguchi, K., 97 Yamaguchi, R., 193 Yamaizumi, Z, 256 Yamaji, N., 176 Yamamoto, H., 8 Yamane, T., 21 Yamashita, M., 121 Yamauchi, K., 1 1 1 Yamazaki, H., 130 Yang, K. U., 143 Yang, S.-L. L., 138 Yano. E.. 197 Yano; J.,'197 Yap, N. T., 243 Yarbrough, L. R., 187 Yarkova. E. G.. 102 Yarnell, T. M.,'237 Yaroshevskii, A. B., 45

Author Index Yasuda, H., 18, 62 Yee, D., 176, 184, 185 Yeh, E.-S., 2 Yip, K. F., 187, 198 Yoda, N., 10 Yokayama, Y., 18 Yokoyama, S., 256 Yokoyama, Y., 234 Yona, I., 17 Yoneda, S., 81, 106 Yonezawa, - Y . , . 8 2 Yoshida, H., 17, 121, 247 Yoshida. M.. 167. 193 Yoshida: Z.,'81, I06 Yoshifuji, M., 69, 102, 126 Yoshii, E., 118 Yoshimura, J., 82 Yoshimura, T., 261 Yoshioka, H., 110 Yoshizawa, T., 164 Younas, M., 143 Young, R . N., 214 Yurchenko, V. G., 259 Yurchenko, R. I., 259 Zabirov, N. G., 115, 116 Zaccai, G., 257 Zakharkin, L. I., 257 Zakharov. L. S.. 244 Zakharov: V. I . , ~ 8 8 ,102, 123 Zaki, M. T. M., 251 Zamkova, V. V., 258 Zanobini, F., 5 Zarytova, V. F., 15 Zatorski, A., 106, 226 Zavlin, P. M., 118, 121, 260 Zawadskii, S., 256 Zbaida, S., 34 Zbiral, E., 16, 23

Zeiss, W., 32, 98, 255 Zeleneva, T. P., 80, 107, 244 Zemlicka, J., 197 Zevely, E. M., 188 Zhdanov, R. I., 168, 253 Zhigarev, G. G . , 257 Zhmurova, I. N., 259 Ziegler, J.-C., 14 Zielinska, B., 98 Zielinski, W. S., 165, 166, 174 Ziemnicka, B., 257 Zilch, H., 224 Zimer, M. H., 240 Zimin, M. G., 96, 115, 116, 242

Zimmer, H., 120, 225, 232 Zimmer-Gasse, B., 6, 22, 209. 254 Zindler, G., 95 Zmudzka, B., 188 Zoellner. N., 261 Zon, G., 99, 118, 256 Zontova, V. N., 246 Zoretic, P. A., 234 Zozulin, A. J., 250 Zschunke, A., 116 Zuckerman, J. J., 1 1 Zuev, M. B., 242, 252 Zuikova, A. N., 13, 63, 247 Zurabyan, N. Zh., 123 Zveguintzoff, D., 75 Zverev, V. V., 253 Zwaschka, F., 47 Zwierzak. A.. 97. 119. 126. 256 Zyablikova, T. A,, 13, 63, 246, 247, 257 Zvkov. 1. N.. 41 Zykova, T. V., 51, 52,242 ,

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Organophosphorus Chemistry

Organophosphorus Chemistry

Organophosphorus Chemistry