Heterocyclic Chemistry Volume 1 Edition. ed. Edition

A Review of the Literature Abstracted Between July 1978 and June 1979

By H. Suschitzky, O. Meth-Cohn

The Royal Society of Chemistry

Copyright © 1980 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-970-4

Contents

Chapter 1 Three-membered Ring Systems By T. J. Mason, 1,
Chapter 2 Four-membered Ring Systems By R. C. Storr, 45,
Chapter 3 Five-membered Ring Systems By G. V. Boyd, P. A. Lowe, and S. Gronowitz, 67,
Chapter 4 Six-membered Ring Systems By G. P. Ellis and R. K. Smalley, 257,
Chapter 5 Seven-membered Ring Systems By D. J. Le Count, 377,
Chapter 6 Eight-membered and Larger Ring Systems By G. M. Brooke, 411,
Chapter 7 Bridged Systems By J. M. Mellor, 439,
Chapter 8 Conformational Analysis By F. G. Riddell, 469,
Author Index, 489,

CHAPTER 1

Three-membered Ring Systems

BY T.J. MASON

The last Report on three-membered heterocyclic rings to appear in one of the Specialist Periodical Reports series concerned only saturated systems and covered material published in 1975.1 The scope of this Report has been extended 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 Oxygen-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 % of Na or K, or 0.003% of Cs or Rb, increase selectivity to around 80%. Selectivity may also be improved by the addition of 1,2-dichloroethane to the gases; this retards the formation of CO2 and H2O. It is reported that HCl (produced by the dehydrochlorination of the chloro-alkane) reacts with chemisorbed atomic oxygen on the silver catalyst to form chemisorbed atomic chlorine. 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 oxygen.

The palladium complex [PdCl2{P(C6F5)3}2] has been found to give a selectivity of more than 60% in the epoxidation of propene. A mixture 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-epoxidation competes with the usual reactions of singlet oxygen, 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; sensitization 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 α-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). The epoxide (4) is directly produced by oxidation of (1) with perbenzoic acid. Dimethylstyrene (5) and tetraphenylporphine (a dye photosensitizer), when irradiated in CCl4 using sodium lamps, react with oxygen to give a mixture of products containing 30% of the diperoxide (6), which on refluxing in benzene gave epoxide (7) (65%).

The cleanest photo-epoxidations occur using α-diketones as sensitizers. The mechanism of the reaction has been investigated by Bartlett, using 18O2, 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 sensitizer yielded little or no epoxide, but resulted in a good and efficient method of converting such compounds into cyclopentenones. The yields of cyclopentenones (10) isolated from the allenes (9; R1 = But, R2 = H), (9; R1 = C5H11,R2 = H), and (9; R1 = C4H9, R2 = H) being 40, 55, and 60%, respectively.

A mechanistic investigation of the acenaphthenequinone-sensitized photoepoxidation of alkenes has been reported. Photolysis of the quinone in dichloromethane that was continuously saturated in oxygen generated 1,8-naphthalic anhydride in 80% isolated yield. When cyclohexene was included in 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 (11) obtained by either C– or O-oxidation. It was suggested that this intermediate could yield O3 by f urther reaction with O2 and thus account for the small amount of adipaldehyde formed in the reaction.

Oxidation of Alkenes to Oxirans by Peroxy-acids. The use of peroxyacids in the epoxidation of unsaturated compounds has been reviewed. Vinyloxiran (12) was prepared in 95% yield by the reaction of peroxypropanoic acid with butadiene in benzene at 40 °C. The same peroxy-acid, continuously generated by the reaction of propanoic acid with hydrogen peroxide, has been used in the epoxidation of propene in tetrachloroethene and 1,2-dichloropropane. The epoxides of a variety of cyclohex-2-enyl halogenoacetates (13; R = Me, ClCH2,Cl2CH, Cl3C, or BrCH2) may be prepared in 53–75% yield by the reaction of the corresponding alkenes with peroxyacetic acid. For these epoxidations, a correlation exists between log k and τ*. Substituents (R1 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 σ-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; R1R2 = O), (14; R1 = OMe, R2 = H), and (14; R1 = 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 (OITS).

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, as have the prospects for the large-scale use of such methods.

The stereochemistry of [VO(acac)2]-catalysed epoxidation of cyclic allylic alcohols with ButOOH has been examined and compared with that obtained using m-ClC6H4CO3H as oxidant. This investigatior followed an earlier observation that the former system showed high cis selectivity for allylic alcohols wittt a medium-sized ring whereas the latter showed predominantly trans selectivity with such substrates. In the case of the cyclonon-2-enols (16)(Z) and (17) (E), both gave an 83% epoxide yield, consisting of >90% cis-isomer, using ButOOH and [VO(acac)2] whereas a 90% epoxide yield was obtained with m-ClC6H4CO3H in each case, consisting of 99.8 and 90% trans-isomer respectively. For five- and six-membered-ring allylic alcohols, both reagents gave predominantly cis-products.

The product distributions in the [Mo(CO)6]-catalysed epoxidation of esters of farnesol (18) and geranylgeraniol by ButOOH are influenced by phenyl-dimethylcarbinol templates. Thus the ratio of 6,7- to 10,11-epoxides may be changed from 40: 60 for a para– to 17 :83 for a meta-dimethylcarbinol substituent. 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).

Molybdenum powder has been used as a catalyst to provide highly selective epoxidations of hex-1-ene, oct-1-ene, and cyclohexene with ButOOH. The kinetics and mechanism for the reaction were reported; the rates correlated with the ionization potentials of the alkenes. Kinetic studies have also appeared for the epoxidation, by cumene hydroperoxide, of styrene, using (RO)3B catalysts (R = Pr or Bu), and of isobutene, using [Mo(acac)3] catalyst.

Hydrogen peroxide has been used to epoxidize cyclohexene in >85% yield and 87% selectivity, using either [Mo(CO)6] or B2O3 as catalyst. Seleninic acids RSe(O)(OH) [R = Ph, 2-NO2C6H4, or 2,4(NO2)2C6H3] have also proved effective catalysts with this oxidant. Thus (21;R = H) and (21;R = Me) were prepared in 91–94% yield and cyclodecene oxide in 87% yield. The novel stereochemical feature of [Fe(acac)3]-catalysed oxidation of either cis– or trans– stilbene by H2O2 is the production of the trans-epoxide (22) from either. This catalyst system, when applied to the methyl esters of higher unsaturated fatty acids, also consistently gave trans-epoxides.

Halohydrin Cyclizations and Related Reactions. A general synthesis of oxirans has been described which involves a cyclization of β-hydroxydimethylsulphonium salts (24) with base. The method applied to the synthesis of phenyldimethyloxiran (25) in 68% yield is shown in Scheme 2, starting from the α-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.

The oxiran (28) was prepared from the alcohol (26) by sequential reaction with CCl4 and azobisisobutyronitrile, and after heating for 15 hours this gave (27) (72%), which was dehydrochlorinated with NaOH in methanol. The reaction of R1Br(R1 = Ph, p-tolyl, benzyl, α-naphthyl, or p-anisyl) with Mg and Se gave R1SeMgBr, which reacted with epichlorohydrin to form (29); this, with KOH in diethyl ether, gave the corresponding selenyl epoxide (30): (31) was prepared from 2-methylepichlorohydrin. A number of 2-halogeno-ketones (32; R1 = Me, Pri, or Ph; R2 = H, Me, or Ph; R3 = Me or Ph; X = Cl or Br) reacted with Et4N+CN- in CH2Cl2 (or MeCN) at 40–80°C to give the oxirans (33). The reagent 2,4,4,6-tetrabromocyclohexadienone (TBCO) selectively bromohydroxylated squalene to yield, by reaction with NaOH, the 2,3-epoxide and the 2,3:22,23-diepoxide. 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 methanolic NaOH. The reaction proceeds through a Darzens-type mechanism via the anion (35), followed by subsequent elimination of bromide ion by the oxy-anion in (36) (Scheme 3).

A new strategy for the formation of αβ-epoxy-esters has been reported which gives a remarkably stereochemically pure product; the least-hindered oxiran. Thus a β-hydroxy-ester, e.g. (38), reacts with Pri2NLi 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.

Carbanions derived from α-chloro sulphur compounds may be used in condensation reactions with carbonyl compounds. Thus the epoxy-sulphimines (42) may be synthesized from the reaction of the chloro-sulphoximine (41), using R1R2CO[R1, R2 = Me, Me or H, Ph; R1R2 = (CH2)5 or (CH2)2CHBut(CH2)2] in the presence of KOBut. The epoxyalkane-sulphonamides (44; R1 = R2 = various alkyl and aryl groups) are prepared by the reaction of sulphonylmorpholines (43; R1 = H, Ph, or Pr) with the corresponding carbonyl compound.

Synthesis of Chiral Oxirans. A general method for the synthesis of chiral epoxides of high enantiomeric purity is outlined in Scheme 4. The method starts with the opening of racemic epoxides with sodium thiophenoxide to produce β-hydroxysulphides (45; R1, R2, R3 = alkyl or aryl), followed by chromatographic separation (on neutral or basic alumina) of the diastereomeric carbamates derived by the reaction of (45) with enantiomerically pure 1-(1-naphthyl)ethyl isocyanate. After cleavage by silanolysis (80–90%), the pure β-hydroxy-sulphides are converted into chiral oxirans upon treatment with [Me3O]+BF4- followed by alkaline hydrolysis. The method has been applied to the synthesis of (+)-disparlure (46), the sex pheromone of the gypsy moth.

Catalytic asymmetric syntheses of epoxides have been briefly reviewed. 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-l-ol to epoxide (47) by cumene hydroperoxide in 50% chemical and 17% asymmetric yield. 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 ButOOH, using vanadium catalysts.

Wynberg has developed a technique for producing both enantiomers of a variety of oxirans under phase–transfer conditions, using salts of the Cinchona alkaloids. Chiral oxirans were obtained using the following methods: (a) 28% hypochlorite, (b) Darzens, (c) racemic halohydrin cyclization, and (d) addition of cyanide to α-halogeno-ketones, using quinininium benzyl chloride (QUIBEC) (48) as the catalyst. In the phase-transfer chiral epoxidation of (49) with H2O2 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 solvent.

Partial asymmetric synthesis of substituted trans-2,3-diaryl-oxirans has been achieved, using chiral arsonium ylides. 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, respectively.

Synthesis of Fused 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) and (52) has appeared, starting from the adduct of benzyne with trans, trans-1,4-diacetoxybutadiene (50). The chrysene bay-region anti-diol-epoxide (53) has been synthesized from chrysene. 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 diequatorial.

(Continues…)Excerpted from Heterocyclic Chemistry Volume 1 Edition. ed. Edition by H. Suschitzky, O. Meth-Cohn. Copyright © 1980 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.