Heterocyclic Chemistry Volume 1 pot

Catalytic Oxidation of Alkenes, using Peroxides Halohydrin Cyclizations and Related Reactions Syntheses Related to the Darzens Reaction Synthesis of Chiral Oxirans Synthesis of Fused Aro

Heterocyclic Chemistry Volume 1

A Specialist Periodical Report

~~

Heterocyclic Chemistry

Volume 1

A Review of the Literature Abstracted

between July 1978 and June 1979

Senior Reporters

H Suschitzky and 0 Meth-Cohn Department of Chemistry and Applied Chemistry, University of Salford

Reporters

G V Boyd Chelsea College, London

G M Brooke University of Durham

G P Ellis UWIST, Cardiff

S Gronowitz University of Lund, Sweden

D Le Count ICI Pharmaceuticals, Macclesfield, Cheshire

P A Lowe University of Salford

T J Mason Lanchester Polytechnic, Coventry

J M Mellor University of Southampton

F G Riddell University of Stirling

R K Smalley University of Salford

R C Storr University of Fiverpool

The Royal Society of Chemistry

British Library Cataloguing in Publication Data

The Royal Society of Chemistry

All Rights Reserved

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

Set in Times on Linotron and printed offset by

J W Arrowsmith Ltd., Bristol, England

Made in Great Britain

In trod uc tion

Heterocyclic Chemistry represents a vast and important area of research which is

of interest to a wide spectrum of chemists This is amply documented by the fact that various journals, societies, and interest groups have sprung up entirely devoted to the pursuit of heterocyclic chemistry Surprisingly though, there exists

to our knowledge no single periodical review alerting the reader on an annual

basis to important developments of the subject We have now been able to persuade the Royal Society of Chemistry to allow us to remedy this omission with the help of eleven specialists This new series of Specialist Periodical Reports, apart from making economic sense, will facilitate the finding of information on heterocyclic topics since it combines the material previously reviewed in a piecemeal way in three different series of volumes These were ‘Saturated Heterocyclic Chemistry’, ‘Aromatic and Heteroaromatic Chemistry’ (both of which are now discontinued), and the still thriving volume on ‘Organic Compounds of Sulphur, Selenium, and Tellurium’, which has surrendered its heterocyclic parts but will continue to report on P-lactam antibiotic chemistry The literature coverage is essentially based on volumes 89 and 90 (i.e July 1978

to June 1979) of Chemical Abstracts, but, in order to provide continuity between

this new series and previous (now deleted) reports, the period covered in certain chapters was extended accordingly Our authors have endeavoured to include all significant contributions in a selective and concise rather than an encyclopaedic manner

We have retained the newly introduced format of Volume 7 of the series

‘Aromatic and Heteroaromatic Chemistry’, i.e proceeding from small to large

rings and giving preference to the smaller heterocycle in fused systems Excep- tionally, if the smaller ring is trivial to the chemistry of the annelated system, the larger ring is given priority In cases of uncertainty, both ring-chapters will carry the information, as we felt this to be a justified overlap Articles on ‘Bridged Systems’ and ‘Conformation’ have been added because of their relevance to the chemistry of saturated heterocycles Review references are mostly quoted at the beginning of each chapter, and the contents list has been drawn up with the aim of serving as a broad index for easy location of points of interest In future issues it is hoped to follow similar schemes in each chapter as far as possible We intend to include reviews on specific topics of current interest from time to time

Our authors provided us with the manuscripts in good time and we thank them and the editorial staff of the Royal Society of Chemistry for their efficiency, which made our own task a pleasure

vi Introduction

The Senior Reporters, as always, would welcome comments, criticism, and suggestions concerning this new venture

H SUSCHITZKY & 0 METH-COHN

Postscript: Owing to a printers’ dispute, the publishing date of this volume was considerably delayed This is much regretted Volumes in this series are normally scheduled to appear in the early Summer

H.S & 0.M.-C

Catalytic Oxidation of Alkenes, using Peroxides

Halohydrin Cyclizations and Related Reactions

Syntheses Related to the Darzens Reaction

Synthesis of Chiral Oxirans

Synthesis of Fused Aromatic Oxides

With oxygen and nitrogen nucleophiles With carbanions

Reduction and Elimination

Thermal and Photochemical

With Organometallic Compounds

via Ring Contraction

Spectroscopic and Theoretical Studies

Reactions

Retention of the Aziridine Ring

Ring-opening to Acyclic Compounds

Formation of other Ring Systems

Cyclization to Five- and Six-membered Heterocyclic

Systems With Metal Carbonyls

2 Systems containing One Nitrogen Atom

Azetidines and Azetines

Azetidinones

3 Systems containing Two Nitrogen Atoms

4 Systems containing One Oxygen Atom

Oxetans

2-Oxetanones (p-Lactones)

Dioxetans

5 Systems containing Two Oxygen Atoms

6 Systems containing Sulphur

7 Miscellaneous

Chapter 3 Five-membered Ring Systems

By G V Boyd, P A Lowe, and S Gronowitz

Cycloadditions and Photochemistry

The Structure and Reactions of Hydroxy-, Mercapto-, and Amino-thiophens

Side-chain Reactivities

Carbene and Nitrene Reactions

‘Benzylic’ Reactivity

Reactions of Thiophen Aldehydes and Ketones

Reactions of Carboxy- and Cyano-thiophens

Various Side-chain Reactions

Reaction at Sulphur: Thiophen Dioxides

Di- and Tetra- hydrothiop hens

Bi- and Poly-heterocycles

Naturally Occurring Thiophens

Thiophen Analogues of Steroids

Thiophens of Pharmacological Interest

3 Benzothiophens and their Benzo-fused Systems

Pharmacologically Active Compounds

4 Thiophen Analogues of Polycyclic Aromatic

Hydrocarbons

Analogues of Phenanthrene

Analogues of Phenalenes and Phenalenium Ions

Thiophen-fused Tropylium Ions and Related Compounds

5 Thiophens Fused to Five-membered Heteroaromatic Rings

Thiophen- and Pyrrole-fused Thiophcns,

Pyrazole-, Thiazole-, and Isothiazole-fused Thiophens and Related Compounds

and Related Systems

6 Thiophens Fused to Six-membered Aromatic

Heterocyclic Rings

Thiophen Analogues of Quinoline

Thiophen Analogues of Isoquinoline

X Heterocyclic Chemistry

Pyrimidine-fused Systems

Pyrazine- and Triazine-fused Systems

Miscellaneous Fused Systems

7 Selenophens and Tellurophens

Monocyclic Selenophens

Benzoselenophens and their Benzo-fused Derivatives

Selenophens Fused to Five-membered Aromatic Rings

Selenophens Fused to Six-membered Aromatic Rings

Tellurophens

Tel I u r i u m

B y P A Lowe

Part II Systems containing Nitrogen and Sulphur, Selenium, or

1 Introduction and Reviews

2 Isothiazoles

Synthesis

From Oxathiazolones (Type B)

From Meso-ionic 1,3,2-0xathiazolium-5-olates (Type B)

From P- Amino-cinnamates (Type C)

From Enamines and Isothiocyanates (Type C)

From Benzothiazolyldithioazetidinone (Type C)

From Thione-S-imides (Type D)

From Enamines and Perchloromethanethiol (Type E)

From y- Hydroxy-alkenesulphonamides (Type F)

Isothiazolo[4,5-b]pyrazines

C yclohep t a[ c ]is0 t hiazole

P yrido[ 3’, 2’ : 4,5] thieno[ 3,2 - c ]is0 t hiazole

Reactions of Thiazolium Salts

Reactions of Meso-ionic Thiazoles

14 Condensed Ring Systems incorporating Thiazole

Structures comprising Two Five-membered Rings ( 5 3 )

Thiazolo-[2,3-a]- and -[3,4-b]- isoquinolines

Naphtho-[1,2-d]- and -[2,1-d]-thiazoles [C3NS-C6-C6]

Six-membered Rings (5,6,6)

[C3NS-C4N2-C50]

[C,NS-C,N -C6]

[ C3NS-CSN-CJ Other Condensed Systems incorporating Thiazole

15 Thiadiazoles and Selenadiazoles

Benzimidazoles and other Annelated Imidazoles

5 Systems containing Two Different Heteroatoms

Oxathioles and Oxaselenoles

6 Systems containing Three Identical Heteroatoms

7 Other Systems containing Three Heteroatoms

Other Systems in which Two of the Three Heteroatoms

Systems containing Three Different Heteroatoms

xvi Heterocyclic Chemistry

8 Systems containing Four Heteroatoms

Penta- and Hexa-aza-compounds

Mixed Oxygen, Nitrogen Systems

Other Mixed Systems

Penta- and Poly-aza-compounds

Compounds containing Oxygen and Nitrogen

Other Mixed Systems

11 Compounds containing Fused Five- and Seven-

Chapter 4 Six-membered Ring Systems

Part I Azines, Oxazines, and Thiazines

Con ten fs xvii

Quinoline, Isoquinoline, and their Benzo- and Hydro-

3 Diazines and their Hydro- and Benzo-derivatives 293

5 Oxazines, Thiazines, and their Benzo-derivatives

6 Oxa- and Thia-diazines and Related Systems

323

327

Part II Other Six-membered Ring Systems

By G P Ellis

1 Books and Reviews

2 Systems containing One Oxygen or Sulphur Atom

Thiochromans, Thiochromenes, Thiochromanones,

Flavans and Isoflavans

xviii Heterocyclic Chemistry

Thioxanthenes

Xanthones

3 Systems containing Two or More Oxygen or Sulphur

Atoms

Oxathians and their Benzo-derivatives

Dioxans and Benzodioxans

Dithians and Related Compounds

Systems consisting of Two or More Oxygen-containing

Rings Cannabinoids

Rotenoids

Other Natural Compounds

Synthetic Compounds

Systems containing Oxygen and Sulphur in Different Rings

4 Systems containing Phosphorus as a Heteroatom

5 Systems containing Silicon or Selenium as Heteroatoms

Chapter 5 Seven-membered Ring Systems

By D J Le Count

1 Introduction

2 Reviews

3 Systems containing One Heteroatom

One Nitrogen Atom

One Oxygen Atom

One Sulphur Atom

Other Systems

4 Systems containing Two Heteroatoms

Two Nitrogen Atoms

Nitrogen and another Heteroatom

0 t her Systems

5 Systems containing Three or More Heteroatoms

Chapter 6 Eight-membered and Larger Ring Systems

By G M Brooke

1 Eight-membered Rings

One Heteroatom

Two Heteroatoms

Three or More Heteroatoms

2 Nine- and Ten-membered Heterocycles

Contents

3 Macrocycles

Systems containing Nitrogen only

One Nitrogen Atom

Two or Three Nitrogen Atoms

Four Nitrogen Atoms

Five or More Nitrogen Atoms

Systems containing Nitrogen and Other Heteroatoms

Systems containing Heteroatoms other than Nitrogen

Crown Ethers and Related Compounds

Syntheses

Effects on Chemical Reactions

Reactions of the Macrocyclic Rings

Formation of Host-Guest Complexes

Chapter 7 Bridged Systems

By J M Mellor

1 Introduction

2 Reviews

3 Physical Methods

X-Ray and Neutron Diffraction

Photoelectron Spectroscopy and Related Electrochemical

Nuclear Magnetic Resonance Spectroscopy

Electron Spin Resonance Spectroscopy

xx Heterocyclic Chemistry

7 Bridged Annulenes and Related Systems

8 Cyclophanes

9 Cryptands and Cryptates

Chapter 8 Conformational Analysis

to include unsaturated systems, and some articles published between 1975 and the current review have been included here to attempt to bridge the gap in coverage

1 Oxirans

Preparation.-Catalytic Oxidation of Alkenes to Oxirans, using Oxygen or O x y -

gen-containing Gases The use of supported silver catalysts for the gas-phase

epoxidation of ethene continues as an area of active investigation Improvements

in the selectivity of the reaction may be attained by doping the silver with trace quantities of other metals; e.g., 0.2 atom O/O of Na or K, or 0.003% of Cs or Rb, increase selectivity to around ~ O O / O ~ Selectivity may also be improved by the

addition of 1,2-dichloroethane to the gases; this retards the formation of CO, and

H 2 0 It is reported that HCI (produced by the dehydrochlorination of the chloro-alkane) reacts with chemisorbed atomic oxygen on the silver catalyst to form chemisorbed atomic ~ h l o r i n e ~ The kinetics of such a reaction, in the presence of dichloroethane, have been reported, and rates of both oxidation and epoxidation depend on the concentrations of ethene and ~ x y g e n ~

The palladium complex [PdCl,{P(C,F,),},] has been found to give a selectivity

of more than 60% in the epoxidation of ~ r o p e n e ~ A mixtiire of 43.1% propene,

54.4% hydrogen, and 2.5% oxygen was passed through the catalyst in 1,2- dichlorobenzene and water at 67 “C and 15.8 atm pressure; no carbon dioxide was formed

Photosensitized epoxidation has received considerable attention over the past few years Since 1974, many cases have been reported in which photo-epoxida-

T J Mason, in ‘Saturated Heterocyclic Chemistry’, ed G Pattenden, (Specialist Periodical Reports), The Chemical Society, London, 1978, Vol 5, p 1

W D Mross, E Titzenthaler, M Schwarzmann, and J Koopman, Ger Offen 2 704 197 (Chem Ah., 1978,89, 163 381)

P Kripylo, L Gerber, P Muench, D Klose, and L Beck, Chem Tech (Leiprig) 1978, 30, 630

(Chern Abs., 1979,90,103 080)

A Gawdzik and J Wasilewski, Chem Stosow., 1978,22,13 (Chem Abs., 1978,89 89 924)

’ P N Dyer, Ger Offen 2 746 812 (Chem Abs., 1978,89,43 091)

1

2 Heterocyclic Chemistry

tion competes with the usual reactions of singlet oxygen,6 the reaction being influenced by, among other factors, the nature of the photosensitizer.' An example is the reaction of bisadamantyl with oxygen in acetone solvent; sensi- tization by methylene blue yields more than 95% of 1,2-dioxetan whereas more than 95% of the epoxide is formed with rose bengal as sensitizer The photo- oxygenation of a-pyronene (1) with tungsten lamps using methylene blue yields peroxide (2), which may be reduced by Ph3P, in a low-yield reaction, to the

epoxide (3).8 The epoxide (4) is directly produced by oxidation of (1) with perbenzoic acid Dimethylstyrene (5) and tetraphenylporphine (a dye photosen- sitizer), when irradiated in CCl, using sodium lamps, react with oxygen to give a mixture of products containing 30%

benzene gave epoxide (7) (65%).'

of the diperoxide (6 ) , which on refluxing in

0

The cleanest photo-epoxidations occur using a-diketones as sensitizers l o The mechanism of the reaction has been investigated by Bartlett, using for the epoxidation of norbornene." With benzil or biacetyl as sensitizers, the results suggested the intermediacy of a diradical species such as (8; R = Me or Ph) in the reaction Attempted photo-epoxidation of vinyl-allenes using biacetyl as sensi- tizer yielded little or no epoxide, but resulted in a good and efficient method of converting such compounds into cyclopentenones.12 The yields of cyclo- pentenones (10) isolatedfrom the allenes (9; R 1 = But, R2 = H), (9; R' = C5Hll,

R2 = H), and (9; R' = C4H9, R2 = H) being 40, 55, and 6O%, respectively

A mechanistic investigation of the acenaphthenequinone-sensitized photo-

epoxidation of alkenes has been r e p 0 ~ t e d l ~ Photolysis of the quinone in dichloromethane that was continuously saturated in oxygen generated 1,s-

naphthalic anhydride in 80% isolated yield When cyclohexene was included in

P D Bartlett and M S Ho, J A m Chem SOC., 1974,96,627

C W Jefford and A F Boschung, Helu Chim Ada, 1977,60, 2673

W Cocker, K J Crowley, and K Srinivasan, J Chem Soc., Perkin Trans 1, 1978, 159

M Matsumoto and K Kuroda, Japan Kokai 78 68 789 (Chem Abs., 1978,89, 197 559)

lo N Shimizu and P D Bartlett, J A m Chem SOC., 1976,98, 4193

l 1 P D Bartlett and 3 Becherer, Tetrahedron Lett., 1978,2983

l2 M Malacria and J Gore, J Org Chem 1979,44,885

J-Y Koo and G B Schuster, J Org Chem., 1979,44, 847

Three-membered Ring Systems 3

the reaction solution it was converted into a mixture of oxidized products consisting mainly of allylic hydroperoxide (40%) and epoxide (33%) A possible

mechanism was proposed (Scheme 1) involving the diradical intermediate (1 1) obtained by either C- or O-oxidation It was suggested that this intermediate

could yield O3 by further reaction with O2 and thus account for the small amount

of adipaldehyde formed in the reaction

0

a \ /

Oxidation of Alkenes to Oxirans by Peroxy-acids The use of peroxy-acids in the

epoxidation of unsaturated compounds has been r e ~ i e w e d ' ~ Vinyloxiran (12) was prepared in 95% yield by the reaction of peroxypropanoic acid with butadiene in benzene at 40 OC.15 The same peroxy-acid, continuously generated

by the reaction of propanoic acid with hydrogen peroxide, has been used in the

'* E L Gershanova, E I Stratonova, M F Sorokin, and Z A Mikhitarova, Deposited Document

l5 G Rauleder, H Seifert, H Waldmann, W Schwerdtel, and W Swodenk Ger Offen 2 734 242

1976, VINITI 792 (Chem A h , 1978,88,61683)

(Chem A h , 1979,90, 168 429)

4 Heterocyclic Chemistry

epoxidation of propene in tetrachloroethene and 1,2-dichloropropane l6 The epoxides of a variety of cyclohex-2-enyl halogenoacetates (13; R = Me, ClCH2, C12CH, C13C, or BrCH2) may be prepared in 53-75% yield by the reaction of the corresponding alkenes with peroxyacetic acid." For these epoxidations, a cor- relation exists between log k and T * Substituents (R' and R2) have been shown

to have a marked effect on the rate of epoxidation of (14) to (15), even though

they are separated from the alkene double bond by four 0-bonds." If the rate of epoxidation of the unsubstituted alkene (14; R1 = R2 = H) by peroxy-m- chlorobenzoic acid at 22 "C in dichloromethane is taken as unity, then the relative rates of epoxidation of (14; R'R2 = 0), (14; R' = OMe, R2 = H), and (14;

R' = H, R2 = OMe) are 0.04, 13.2, and 0.36, respectively These results are in accord with predictions based on the concept of orbital interactions through space

A useful crystalline substitute for peroxytrifluoroacetic acid has been found to

be 3,5-dinitroperoxybenzoic acid.*' The major advantages are that ( a ) no buffers

are needed and ( b ) the crystalline material may be stored for up to 1 year at

-10 "C without noticeable loss of reactivity Though perhaps not quite so reactive

as peroxytrifluoroacetic acid, the yields of epoxides from both peroxy-acids are comparable

Catalytic Oxidation of Alkenes to Oxirans, using Peroxides The kinetics and

mechanisms of epoxidation of alkenes by organic hydroperoxides have been reviewed,*l as have the prospects for the large-scale use of such methods.22 The stereochemistry of [VO(a~ac)~]-catalysed epoxidation of cyclic allylic alcohols with Bu'OOH has been examined and compared with that obtained

observation that the former system showed high cis selectivity for allylic alcohols witH a medium-sized ring whereas the latter showed predominantly trans selec-

tivity with such In the case of the cyclonon-2-enols (16) ( 2 ) and (17)

( E ) , both gave an 83% epoxide yield, consisting of >90% cis-isomer, using Bu'OOH and [ V O ( a ~ a c ) ~ ] whereas a 90% epoxide yield was obtained with ( o I T s ) ~ ~

l 6 A M Hildon, T D Manly, and A J Jaggers, Ger Offen 2 747 762; and A M Hildon and P F

l 7 I L Osipenko, D V Lopatik, N G Bulatskaya, and I P Prokopovich, Vestsi Akad Navuk BSSR,

Is M N Paddon-Row, H K Patney, and R N Warrener, J Chem SOC., Chem Commun., 1978,296

l9 M N Paddon-Row, Tetrahedron Lett., 1972, 1409

*' W H Rastetter, T J Richard, and M D Lewis, J Org Chem., 1978, 43, 3163

2 1 S B Grinenko and V M Belousov, Metallokompleksnyi Katal., 1977,40 (Chem Abs., 1978,89,

22 M I Farberov, Khim Prom-st (Moscow), 1979, No 1, p 8 (Chem A h , 1979,90, 203 777)

23 T Itoh, K Jitsukawa, K Kaneda, and S Teranishi, J A m Chem SOC., 1979, 101, 159

Greenhalgh, Ger Offen 2 747 761 (Chem A h , 1978,89,24 123 and 24 124)

Ser Khim Nuuuk, 1978,118 (Chem A h , 1978,89,24060)

23 239)

Three-membered Ring Systems 5

rn-C1C6H4CO3H in each case, consisting of 99.8 and 90% trans-isomer respec- tivelỵ For five- and six-membered-ring allylic alcohols, both reagents gave predominantly cis-products

The product distributions in the [MO(C0)6]-CatalySed epoxidation of esters of farnesol (18) and geranylgeraniol by ButOOH are influenced by phenyl-

dimethylcarbinol tern platệ^^ Thus the ratio of 6,7- to 10,ll-epoxides may be

changed from 40 : 60 for a para- to 17 : 83 for a meta-dimethylcarbinol substi- tuent Together with the results from other templates, the authors have concluded that the simplest terpene conformation consistent with the data is one in which the carbon chain is U-shaped; the template is thought to fold back along one of the legs of the U, as shown in (19) The hydroxy-group of the aromatic substituent serves to co-ordinate with the catalyst (20)

Pr or Bu),*’ and of isobutene, using [ M ~ ( a c a c ) ~ ] catalyst.28

25 R Breslow and L M Maresca, Tetrahedron Lett., 1978, 887

26 Ỵ Kurusu, R Kaya, and N Ishii, Nippon Kagaku Kaishi, 1978, 9, 1262 (Chem Abs., 1978,89,

27 Ạ Badev, D Mondeshka, and D Dimitrov, Khim Ind (Sofia), 1978,435 (Chem Abs., 1979,90,

’* Ẹ Costa Novella, P J Martinez de la Cuesta, Ẹ Rus Martinez, and G Galleja Pardo, A n Quim.,

196 678)

186 058)

1977,73,1192,1198 (Chem A h , 1978,89,129 000,128 828)

6 Heterocyclic Chemistry

Hydrogen peroxide has been used to epoxidize cyclohexene in >85% yield and

87% selectivity, using either [Mo(CO)~] or B2O3 as catalyst.29 Seleninic acids RSe(O)(OH) [R = Ph, 2-N02C,&, or 2,4-(N02)2C6H3] have also proved effective catalysts with this ~ x i d a n t ~ ' Thus (21; R = H) a'id (21; R = Me) were prepared in 91-94% yield and cyclodecene oxide in 87% yield The novel

stereochemical feature of [Fe(a~ac)~]-catalysed oxidatioi- a€ either cis- or trwcs- stilbene by H 2 0 2 is the production of the truns-epoxide (22) from either.31 This catalyst system, when applied to the methyl esters of higher unsaturated fatty acids, also consistently gave trans-epoxides

Me Y C H ,CH Ph

Halohydrin Cyclizations and Related Reactions A general synthesis of oxirans

has been described which involves a cyclization of P-hydroxydimethylsulphonium

salts (24) with base.32 The method applied to the synthesis of phenyl- dimethyloxiran (25) in 68% yield is shown in Scheme 2, starting from the

a-sulphenylated ketone (23) For a number of such syntheses the yields are

in the range 64-70%, and the method has also been applied successfully to the

syntheses of cyclopentene and cyclohexene oxides

Reagents: i, NaBH,; ii, MeI; iii, Bu'OK, DMSO

Scheme 2

The oxiran (28) was prepared from the alcohol (26) by sequential reaction with

C C 4 and azobisisobutyronitrile, and after heating for 15 hours this gave (27)

(72%), which was dehydrochlorinated with NaOH in methan01.~~ The reaction of R'Br (R' = Ph, p-tolyl, benzyl, a-naphthyl, or p-anisyl) with Mg and Se gave

29 J P Schirmann and S Y Delavarenne, Ger Offen 2 752 626 and 2 803 791 (Chem Abs., 1978,89,

30 H J Reich, F Chow, and S L Peake, Synthesis, 1978, 299

31 T Yamamatu and M Kamura, J Chem SOC., Chem Commun., 1977,948

59 832 and 163 380)

S Kano, T Yokomatzu, and S Shibuya, J Chem SOC., Chem Commun., 1978,785

32

Three-membered Ring Systems 7

R'SeMgBr, which reacted with epichlorohydrin to form (29); this, with KOH in diethyl ether, gave the corresponding selenyl epoxide (30): (31) was prepared

from 2-methylepi~hlorohydrin.~~~~~ A number of 2-halogeno-ketones (32; R' =

Me, Pr', or Ph; R2 = H, Me, or Ph; R3 = Me or Ph; X = Cl or Br) reacted with Et4N'CN- in CHzC12 (or MeCN) at 40-80°C to give the oxirans (33).36 The

reagent 2,4,4,6-tetrabromocyclohexadienone (TBCO) selectively bromo-

hydroxylated squalene to yield, by reaction with NaOH, the 2,3-epoxide and the 2,3 : 22,23-diepo~ide.~' The technique has also been applied to the epoxidation of methyl farnesate, farnesyl acetate, and farnesol

Syntheses Related to the Darzens Reaction The chromone epoxide (37) has been

prepared from the bromo-ketone (34) by reaction in aqueous methanolis

NaOH.38 The reaction proceeds through a Darzens-type mechanism via the

anion ( 3 9 , followed by subsequent elimination of bromide ion by the oxy-anion

A new strategy for the formation of ap-epoxy-esters has been reported which gives a remarkably stereochemically pure product; the least-hindered ~ x i r a n ~ '

34 F G Casanov, I M Akhmedov, S B Kurbanov, and M M Guseinov, Azerb Khim Zh., 1978,3,

" I M Akhmedov, F G Gasanov, S B Kurbanov, and M M Guseinov, Zh Org, Khim., 1978,14,

'' H Kobler, K H Schuster, and G Simchen, Jusfus Liebigs Ann Chem., 1978, 1946

" I Ichinose, T Hosogai, and T Kato, Synthesis, 1978,605

G A Kraus and M J Taschner, Tetrahedron Lett., 1977,4575

50 (Chem Abs., 1979,90,22 697)

881 (Chem Ah., 1978,89,24 061)

J A Donnelly, M J Fox, and D E Maloney, Tetrahedron Lett., 1978,4691

8 Heterocyclic Chemistry

Thus a P-hydroxy-ester, e.g (38), reacts with PriNLi and iodine in THF at -78 "C to give (39) (48%) A possible explanation for the stereospecificity lies in the addition of iodine to the least hindered side of an intermediate complex (40) followed by elimination of LiI

EtO

,O I Li (40)

various alkyl and aryl groups) are prepared by the reaction of sulphonyl- morpholines (43; R' = H, Ph, or Pr) with the corresponding carbonyl

Synthesis of Chiral Oxiruns A general method for the synthesis of chiral epoxides

of high enantiomeric purity is outlined in Scheme 4.42 The method starts with the

(45) Scheme 4

opening of racemic epoxides with sodium thiophenoxide to produce P-hydroxy-

sulphides (45; R', R2, R3 = alkyl or aryl), followed by chromatographic separa- tion (on neutral or basic alumina) of the diastereomeric carbamates derived by the

40 H G Corkins, L Veenstra, and C R Johnson, J Org Chem., 1978,43,4233

4 1 J Golinski and M Makosza, Synthesis, 1978, 823

Three-membered Ring Systems 9

reaction of (45) with enantiomerically pure l-(l-naphthy1)ethyl isocyanate After

cleavage by silanolysis (80-90%), the pure P-hydroxy-sulphides are converted

into chiral oxirans upon treatment with [Me,O]' BF4- followed by alkaline hydrolysis The method has been applied to the synthesis of (+)-disparlure (46),

the sex pheromone of the gypsy moth

(46)

Catalytic asymmetric syntheses of epoxides have been briefly re~iewed.~' Attempts have been made to introduce chirality by the use of an optically active

catalyst, e.g dioxo(acetylacetonato)[(-)-N-methylephedrinato]molybdenum, in

the oxidation of 3-methylbut-2-en-1-01 to epoxide (47) by cumene hydroperoxide

in 50% chemical and 17 '/o asymmetric yield.44 Alternatively, an optically active

alcohol, e.g (-)-menthol, may be introduced into a system, as in the epoxidation

of cis- or trans-oct-2-ene with Bu'OOH, using vanadium cataly~ts.~'

* Wynberg has developed a technique for producing both enantiomers of a variety of oxirans under phase-transfer conditions, using salts of the Cinchona

hypochlorite, ( b ) Darzens, (c j racemic halohydrin cyclization, and ( d ) addition of

cyanide to a-halogeno-ketones, using quinininium benzyl chloride (QUIBEC)

(48) as the catalyst In the phase-transfer chiral epoxidation of (49) with H 2 0 2 in the presence of (48), the enantiomeric excess (Ee) fell from 54% in benzene to 10% in nitrobenzene in a manner which was inversely related to the dielectric constant of the

(47)

OMe

(49)

CH,Ph

43 K Hermann, Nachr Chem Tech Lab., 1977,25,301,303 (Chem Abs., 1977,87,134 852)

44 S Yamada, S Terashima, and T Masuko, Japan Kokai 78 50 1 1 1 (Chem A h , 1978,89,109 035)

45 R Curci, F Furia, J 0 Edwards, and G Modena, Chim Ind (Milan), 1978 60,597 (Chem Abs.,

10 Heterocyclic Chemistry

Partial asymmetric synthesis of substituted truns-2,3-diaryl-oxirans has been achieved, using chiral arsonium ylide~.~’ For (R,R)-diphenyloxiran, Ee was in the range 5-17%, depending on conditions; an Ee of 38% was achieved for ( R , R ) -

di-(2-methoxyphenyl)oxiran Complexation chromatography has been used in the estimation of the enantiomeric purity of samples of ( + ) - ( R ) - and (-)-(S)-1,2-

epoxypropane prepared from L-alanine and ethyl (-)-(S)-lactate, re~pectively.~’ Synthesis ofFused Aromatic Oxides The interest in both the synthesis and the

biological activity of fused aromatic oxides continues, although only synthetic aspects will be reviewed in this Report.” A new route to naphthalene oxides (51)

diacetoxybutadiene (50).’* The chrysene bay-region anti-diol-epoxide (53) has been synthesized from c h r y ~ e n e ~ ~ The diol-epoxides (54) and (55) have been synthesized and the stereochemistry of the OH groups is diaxial, in contrast to the

analogous derivatives of benzo[a]pyrene, e.g (56), where the preferred con-

formation of the OH groups is d i e q ~ a t o r i a l ~ ~

49 D G Allen, N K Roberts, and S B Wild, J Chern SOC., Chem Comrnun., 1978,346

52 R R Schmidt and R Angerbauer, Angew Chem., 1979,91,325

53 P P Fu and R G Harvey, J Chem SOC., Chern Comrnun., 1978,585

V Schurig, B Koppenhoefer, and W Buerkle, Angew Chem., 1978,90, 993

Poiynuclear Aromatic Hydrocarbons, 1978, p 109 (Chem Abs., 1978,89, 146 793)

Three-membered Ring Systems 11

Miscellaneous Syntheses The biosyntheses of epoxy-terpenes and epoxy-

fatty-acids have been re~iewed,~’ as has the epoxidation of alkenes under enzyme-simulated conditions 56 Terminal alkenes are oxidized biochemically by

Corynebacterium equi to give the corresponding optically pure (+)-(R)-epox-

ides5’ Two-phase fermentation has been used to produce 7,8-epoxyoct-l-ene and 1,2 : 7,8-diepoxyoctane from octane and octa- 1,7-diene, using Pseudomonas

o l e o ~ o r a n s ~ ~

Corey’s reagent, dimethylsulphonium methylide, has been used in the synthesis

of aryl-oxirans, e.g 2-naphthyloxiran (%YO), and under phase-transfer catalysis conditions, e.g 9-phenanthryloxiran ( 9 0 Y 0 ) ~ ~ Stereospecific addition of the reagent to 9,lO-anthraquinone affords the diepoxide (57) (94y0).~’ The sulphur

ylide (58) was prepared by treating cis- and trans-l-thioniabicyclo[4.4.0]decane

bromides with NaH in THF at reflux.61 The ylides reacted with carbonyl

compounds to give epoxides; e.g., with acetone to yield (59) (74%)

~ e l e n i d e s ~ ~ This has allowed the synthesis of (61; R’ = H, R2 = Me) and

(61; R’ = Me, R2 = H) with >95% stereochemical purity from (2)- and (E)-oct-2-ene respectively

R1-H

H

” S Voigt and M Luckner, Pharmazie, 1978,33,632

56 Z Yoshida, Kagaku No Ryoiki, Zokan, 1976, 113, 1 (Chem Abs., 1977, !6,42 532)

57 H Ohta and H Tetsukawa, J Chem SOC., Chem Commun., 1978,849

59 N-C C Yang, W-L Chiang, D Leonov, E Leonov, I Bilyk, and K Bongsub, J Org Chem., 1978,

6o T J McCarthy, W F Connor, and S M Rosenfeld, Synth Commun., 1978, 379

C J McCoy and R D Schwartz, Ger Offen 2 756 287 (Chem Abs., 1978,89,127 778)

43,3425

K Tokuno, F Miyoshi, Y Arata, Y Itatani, Y Arakawa, and T Ohashi, Yakugaku Zasshi, 1978,

98, 1005 (Chems Abs., 1979,90, 6195)

62 M E Garst, J Org Chem., 1979, 44 1578

63 Y Tatsumo, S Otsuka, K Saigo, T Mukaiyama, A Yasuda, H Yamamoto, and N Sonoda, Kagaku

No Ryoiki, Zokan, 1977,117,329 (Chem Abs., 1978,89, 128 540)

12 Heterocyclic Chemistry

A new approach to substituted arene oxides (63) is outlined in Scheme 5.65 A variety of substituents in (62) may be introduced uia alkylation of dilithio-1,4- dihydrobenzoate This method has been incorporated in the total synthesis of the shikimate-derived metabolites senepoxide and seneol from (63 ; R = CHZOCOPh)

Iron-porphine complexes have been used as catalysts in epoxidations using

iodosylbenzene as the oxygen source.66 Using chloro-apy&tetraphenylpor-

phinatoiron(III), cyclohexene yielded 5 5 O/O oxide while cyclohexadiene gave 74%

mono-epoxide It is interesting to note that cis- (but not trans-)stilbene was epoxidized with this catalyst, whereas both isomers were epoxidized using

chlorodimethylferriprotoporphyrin, with complete retention of configuration Iodine(II1) trifluoroacetate has been shown to epoxidize a number of steroidal

a l k e n e ~ ~ ’

Spectra and Theoretical Chemistry of 0xirans.-Bonding and bond-bending in small ring compounds (64; Z = CH2, 0, S, or NH) have been examined, using a b initio FSGO calculations.68 Attempts have been made to predict the reactivity of oxirans towards thermal and photochemical ring-opening and also towards fragrnentati~n.~’ The first hundred mono- and di-excited states of ethene oxide were used to provide the basis for a semi-quantitative rationale of the main

reactivity trends by ab initio SCF calculations Predictions of the properties of arene oxides with relation to their biological importance have been

The steric course of the 1,4-opening of cisnid and transoid diene mono-epoxides incorporated into ring systems has been analysed and interpreted, using torsion- angle notation and assuming the maintenance of orbital overlap during the

r e a ~ t i o n ~ ’

6s B Ganem, G W Holbert, L B Weiss, and K Ishizumi, J Am Chem SOC., 1978,100, 6483

66 J T Groves, T E Nemo, and R S Myers, J A m Chem SOC., 1979,101, 1032

67 M Linskeseder and E Zbiral, Justus Liebigs Ann Chem., 1978, 1076

68 E R Talaty and G Simons, Theor Chim Acta, 1978,48, 331

69 B Bigot, A Sevin, and A Devanquet, J Am Chem SOC., 1979,101, 1095, 1101

’’ M M Marsh and D M Jerina, J Med Chem., 1978,21, 1298

P P Fu, R G Harvey, and F A Beland, Tetrahedron, 1978, 34, 857

7 0

Three-membered Ring Systems 13

An ion cyclotron resonance study of the reaction of CzH40+' ion, from ethene

oxide or 1,3-dioxolan and their deuteriated derivatives, provides support for the

existence of the open oxiran ion (65) as a stable entity in the gaseous phase, in

agreement with theoretical prediction^.^^ Microwave studies of (66) involving

assignments of the normal and the monodeuterio-, dideuterio-, and "0 and 13C

2.89D A study of the polarizability of oxiran and thiiran has resulted in

refinements to the anisotropy of polarizability of the exocyclic C-C bonds in

methyl- and tetramethyl-~xiran.~'

The conformations of the cis- and trans-isomers of 3,4-epoxybicyclo-

[4.1.0]heptane (67) and 1,2 : 4,5-diepoxycyclohexane (68) have been investi-

gated by 'H n.m.r., using [ E ~ ( d p r n ) ~ ] as shift reagent.76 Results indicate that the

cyclohexane ring in both isomers of (67) and in cis-(68) exists in a predominantly

planar conformation; the results for trans-(68) were inconclusive A novel

application of the study of the oxiran ring-current effect is in the determination of

the configuration and conformation of certain epoxy-bicycloalkanones in which

the epoxide is on a five-membered ring.77 Thus two epoxides may be obtained

when the unsaturated @-lactam (69) is epoxidized The oxiran ring in (70) shields

proton Ha, which is transannular to and coaxial with it, whereas no such shielding

The conformations of cis,& 1,3 - cyclo-octadiene and its mono- and di-epox-

ides have been determined, using variable-temperature 'H and 13C n.m.r studies

together with iterative force-field calculation^.^^ The 13C n.m.r spectra for a

number of 5,6-epoxy-steroids have been reported, with the result that the

published spectra for several 5a,6a- epoxides require re-a~signment.~'

Reactions of 0xirans.-The chemical reactivity of epoxides,80.81 the solution

chemistry of arene oxides,82 and the hydrosilylation of epoxy unsaturated

have been reviewed

" W J Bouma, J K Macleod, and L Radom, Nouu J Chim., 1978 2,439; J Chem SOC., Chem

74 C W Gillies, J Mol Spectrosc., 1978, 71, 85

'' B A Arbuzov, L K Novikova-Aleksandrova, S G Vul'fson, and A N Vereshchagin, Izv Akad

76 A Aumelas, E Casadevall, and A Casadevall, Tetrahedron, 1978 34, 2481

77 A S Mubarik, J M Berge, N W Crossland, and S M Roberts, J Chem SOC., Perkin Trans 2

Commun., 1978,724

Nauk SSSR, Ser Khim., 1978,1932 (Chem Abs., 1978,79,179 377)

1978,1205

F A AnetandI Yavari, J A m Chem SOC., 1978,100,7814

S G Wilkinson, Int Rev Sci., Org Chem., Ser Two, 1975, 2, 111

R Oda, Kagaku (Kyoto), 1975,30,968 (Chem Abs., 1 9 7 6 , 8 5 2 0 955)

T C Bruice and P Y Bruice, Acc Chem Res., 1976, 9, 378

79 H L Holland, P R P Diakow, and G R Taylor, Can J Chem., 1978,56,3121

83 S I Sadykhzade and R A Sultanov, in 'Epoksidne Monomery Epoksidne Smoly', ed M S

14 Heterocyclic Chemistry Electrophilic Ring-opening Reactions Kinetic studies A detailed n.m.r study of

the rates of hydrolysis of tetramethyloxiran to pinacol in aqueous buffers has been

The mechanism which was suggested for acid-catalysed ring-opening involves an equilibrium protonation of the oxygen atom, which weakens and lengthens (but does not break) the C - 0 bonds and facilitates attack by water at either tertiary carbon centre The transition state (72) thus obtained includes the

as a guide to the carcinogenicity or mutagenicity of this family of compounds Linked to this topic have been two theoretical papers on the hydrolysis of ethene oxide86 and benzene oxide.”

Cyclization reactions Decalone derivatives (74) (30%) and (75) (25 YO) may

be prepared from the epoxycyclohexanone (73; R = CH=CH2) by treatment

with strong Lewis acids, e.g TiC14 in CH2C12.88 Similar cyclizations occurred using (73; R = CH=CHMe) and (73; R = p-anisyl), the latter producing a 1 : 1 mixture of (76; X = H, Y = OMe) and (76; X = OMe, Y = H) (90°/0) A

related ring closure is that for the acetylenic epoxide (73; R = C G CH ) to (77) (>90%).89 An unexpected cyclization, however, was observed when (73; R =

CH=CMe2) was treated with Lewis acids, giving (78) as a kinetic product that was

84 Y Pocker and B P Ronald, J A m Chem SOC., 1978,100,3122

8 5 T Okarnoto, K Shudo, N Miyata, Y Kitahara, and S Nagata, Chem Pharm Bull., 1978,26,2014;

A R Becker, J M Janusz, R Z Rogers, and T C Bruice, J A m Chem Soc., 1978,100,2244; D

L Whalen, A W Ross, H Yagi, J M Karle, and D M Jerina, ibid., p 5218; J M Janusz, A R Becker, and T C Bruice, ibid., p 8269

P Politzer, K C Daiker, V M Estes, and M Baughman, Int J Quantum Chem., Quantum Biol

Symp 1978,5, 291

E Huq, M Mellor, and E G Scovell, J Chem Soc., Chem Commun., 1978,526

86

87 J E Ferrell and G H Loew, J Am Chem Soc., 1979,101,1385

89 M Mellor, A Santos, E G Scovell, and J K Sutherland, J Chem SOC., Chem Commun., 1978,

Three-membered Ring Systems 15 readily converted into bicyclononane (79).90 The vinyl ether epoxides (80;

R' = R3 = H, R2 = Me) and (80; R' = H, R2 = R3 = Me) cyclized to (81) and (82) respectively on treatment with BF,.Et,O .91 Hydrolysis or cleavage by singlet oxygen of the cyclized products affords a new stereospecific route to carbocyclic ketones and lactones with a medium-sized ring respectively

Cyclizations from ring D epoxy-steroids have been reported; e.g., treatment of

the epoxy-dinorcholenedione enol acetate (83) with AcOH containing H2S04 gave the steroidal furanone (84) and the pyranone (85) Lactone (87) was obtained when the epoxy-norcholenoate (86) was similarly treated with acid.92 A 19-methoxy-group has been found to be a sufficiently good internal nucleophile

to compete with water in the HCIO,-catalysed cleavage of the A- and B-ring

90 E G Scovell and J K Sutherland J Chem SOC., Chem Commun., 1978,529

91 R J Boeckman, K J Bruza, and G R Heinrich, J A m Chem Soc., 1978, 100,7101

q2 A V Kamernitskii, I G Reshetova, and K Yu Chernyuk, Izv Akad Nauk SSSR, Ser Khim.,

1978, 184; A V Kamernitskii, V A Krivoruchko, and I G Reshetova, ibid., p 188 (Chern

16 Heterocyclic Chemistry a-epoxides (88) and (89).93 Adjacent acetate groups have also proved effective as internal nucleophiles in ring-cleavage reactions of steroidal e p ~ x i d e s ~ ~

Bartlett has reported a highly stereoselective synthesis of (*)-a-multistriatin

(91) which, in the last step, involves the Lewis-acid-catalysed cyclization of (90) in

effort to identify the type of norbornyl cation that is generated on acid-catalysed opening of (92) (ex0 and endo), the products have been compared with those obtained on treatment of nortricyclanol with acid.97 For a common nonclassical carbenium ion intermediate, the products from all three compounds would be identical, and in the same ratio Since this was not found, and the ratio of the diols

R' R2

v

(93) R' = H , R 2 = OH

(94) R' = O H , R 2 = H

93 P Kocovsky and V Cerny, Collect Czech Chem Commun., 1979,44, 226

94 E Glotter and P Krinsky, J Chem SOC., Perkin Trans 1 , 1978,413

95 P A Bartlett and J Myerson, J Org Chem., 1979, 44, 1625

96 M Inoue, Y Taguchi, T Sugita, and K Ichikawa, Bull Chem SOC Jpn., 1978, 51,2098

( S ) , 1978, 62

Three-membered Ring Systems 17

(93) and (94) was reversed from exo- and from endo-(92), the authors have

suggested that a secondary carbenium ion is the intermediate involved

Olah has reported a useful reagent, pyridinium poly-hydrogen fluoride, for the preparation of fluorohydrins from e p o x i d e ~ ~ ~ The reaction can be carried out under mild conditions without recourse to heating, and is applicable to both aliphatic and aromatic epoxides

Nucleophilic Ring-opening Reactions New aspects of the nucleophilic ring open-

ing of oxirans have been re~iewed.'~

With oxygen and nitrogen nucleophilks The hydrolyses of a number of

chloro-oxirans have been studied, at 37"C, in aqueous solution buffered at

pH 7.4, the conditions being chosen to mirror the reactivity of an epoxide towards

cellular nucleophiles in uivo loo The reactions obeyed pseudo-first-order kinetics and yielded a-chlorocarbonyl compounds via chlorine migration; thus both cis -

and trans-l,3-dichloropropene oxide gave a-chloroacrylaldeh yde The presence

of chlorine greatly increases the hydrolytic reactivity of aliphatic epoxides, the

rate for trichloroethene oxide being 2 x lo4 times faster than that for ethene

oxide itself For the reaction of benzoic acid with ethene oxide in the presence of

mines, kinetic data and the isolation of intermediates indicate that the catalyst for the reaction is a quaternary salt formed from all three compounds.'o' A Hammett plot for the esterification of (95; R1 = MeO, Me, H, C1, or NO,) to (96)

gave a positive value for p, suggesting that hydrogen-bonding between the epoxide and acid in the transition state has an important accelerating effect The esterification of terephthalic acid with ethene oxide has also been investigated lo2

Isoquinoline reacts with ethene oxide in acetic acid to yield the unstable oxazolidine (98; R = H) via the zwitterion (97).lo3 Using 1-(3-methoxy-2-

nitrobenzyl)isoquinoline, the stable oxazolidine (98; R = 3-MeO-,2-N02- CaH3CH2) was obtained (69%).lo4 Similar treatment of quinoline gave the novel labile compound (99)

Linear free-energy relationship (LFER) studies of the ring-opening reactions

of chalcone epoxides (100; R1 = H; R2 = H, OMe, Me, or Br) and (100;

R' = OMe, Me, Br, or Cl; R2 = H) with morpholine have shown that, for

98 G A Olah and D Meidar, Isr J Chem., 1978, 17, (1-2), p 148

99 N S Enikolopiyan, Pure Appl Chem., 1976,48, 317

loo S A Kline, J J Solomon, and B L Van Duuren J Org Chem., 1978,43, 3596

lo' H Kamatani, Nippon Kuguku Kaishi, 1978,850 (Chem Ah., 1978,89,107 290)

H Kamatani, Nippon KagukuKuishi, 1978,1271 (Chem Abs., 1978,89,214 595);T I Samsonova,

G D Mikhailov, V A Malykh, and A S Chegolya, Khim Volokna, 1978, 15 (Chem Abs., 1978, 89,41849)

C N Filer, F E Granchelli, P Ferri, and J L Neumeyer, J Org Chem., 1979,44,285

lo3 C N Filer, F E Granchelli, A H Soloway, and J L Neumeyer, J Org Chem., 1978,43, 672

18 Heterocyclic Chemistry

variable R1 and R2, p values of -0.64 (50 "C) and +0.455 (70 "C) are obtained, respectively.105 These results are consistent with the expected nucleophilic attack

at the position B to the carbonyl group A number of other reactions of (100;

R1 = H, R2 = C1) and (100; R' = NOz or C1,R2 = Me) with Grignard reagents, A1Cl3, thioureas, and hydrazines have been reported.lo6

R J 1 ( T " Q2 - / \

(100)

Two detailed mechanisms occurring in the reaction of ethene oxide with NMe3.HCI to give [Me3NCH2CH20H]+ C1- have been reported.lo7 Rate constants for four separate stages of the process have been determined, the first step being the dissociation of the amine salt The tetrahydroquinoline derivative (101) reacted with NEt, to give the betaine (102), which underwent thermal rearrangement to (1 03) lo'

epoxide ring is e m , as predicted by the Baldwin rules Carbanion-induced

cyclization of (106; n = 2 or 3) to (107) is achieved by reaction with MeMgI in

lo5 S N Sernenova, S K El-Sadana, V S Karavan, and T J Ternnikova, Zh Org Khim., 1978, 14,

' 0 6 A A Hamed, A Essawy, and M A Salem, Indian J Chem., Sect B, 1978, 16,693

lo' N A Uring, G F Tereshchenko, and L A Lavrent'eva, Zh Obshch Khim., 1979,49,466 (Chern

log H Wittmann and H Siegel, Z Naturforsch., Teil B, 1978,33,429

C K Bradsher and D C Reames, J Org Chem., 1978,43,3800

1268 (Chem Ah., 1978,89,107 686)

A h , 1979 90,203 144)