Arsonium ylides epoxidation

Trippett and Walker (97) found that the reaction of para-substituted benzylidene triphenylarsoranes with carbonyl compounds led to olefins when the benzylidene para substituent is highly electron withdrawing, but otherwise to epoxide. KumaricY al. (64) prepared two new semistabilized arsonium ylides, p-bromo- and p-iodobenzylidene triphenylarsorane, which were treated with a series of carbonyl compounds to yield exclusively trans-olefins. In no case was an epoxide obtained. 

Current results indicate that stabilized arsonium ylides such as phenacylide, carbomethoxymethylide, cyanomethylide, fluorenylide, and cyclopentadienylide afford only olefinic products upon reaction with carbonyl compounds. Nonstabilized ylides such as ethylide afford almost exclusively epoxides or rearranged products thereof. However, semi-stabilized arsonium ylides, such as the benzylides, afford approximately equimolar amounts of olefin and epoxide. Obviously, the nature of the carbanion moiety of the arsonium ylide greatly affects the course of the reaction. It is reasonable to suppose that a two-step mechanism is involved in the reaction of heteronium (P, S, and As) ylides with carbonyl compounds (56). 

Triphenylarsonium ethylide. trans-Epoxides can be prepared stereoselec-tively via arsonium ylides under special conditions (10,445). A simpler method involves transylidation of a phosphonium ylide to an arsonium ylide (equation I).2... 

Arsonium ylides. Semistabilized allylic arsonium ylides are generally not useful in synthesis because they react with carbonyl compounds to form mixtures of epoxides and alkenes. Unexpectedly, the reaction of the semistabilized ylide triphenylarsonium... 

Indeed, in diethyl ether, lithium dimethylcuprate usually reacts with the a-enone group to give a methyl-substituted bromo ketone. Addition of hexamethylphosphoric triamide (HMPT), however, slows down this reaction to such an extent that displacement of the bromo substituent takes place [698], Another remarkable example of the influence of HMPT on chemoselectivity is the reaction of an arsonium ylide, Ph3As= CH-CH=CH-Ph, with benzaldehyde in tetrahydrofuran solution, yielding either an epoxide (in THE) or an alkene (in THF/HMPT) [699],... 

Dialkylamino-aryloxosulfonium alkylides may be employed for enantioselective epoxidation if the ylide with its chiral sulfur center is resolved into its enantiomeric form, " An enantioselective oxirane is obtained by means of a chiral phase-transfer catalyzed procedure with dimethylsulfonium methylide. The utilization of arsonium ylides was reported some time ago. ° A highly stereoselective synthesis of trans-epoxides with triphenylarsonium ethylide has recently been described.Optically active arsonium ylide has been used in the asymmetric synthesis of diaryloxiranes. ... 

By contrast, in another investigation of the reactions between arsonium ylides and aldehydes, it was found that either an alkene or an epoxide was formed, depending upon the identity of the ylide, but not both of them together Both alkenes and epoxides were always trans. This appears usually to be in the case. 

The general pattern which emerged was that stable arsonium ylides provided alkenes whilst reactive arsonium ylides gave epoxides . This was attributed to stabilization of the transition state leading to alkene formation being provided by those same electron-withdrawing groups which stabilized the ylides ... 

Allylic arsonium ylides show a similar pattern of reactivity. Ethoxycarbonylallyl ylides, wherein the ester group is conjugated with the ylidic carbon atom, gave dienes in reactions with aldehydes or ketones , whereas other allylic ylides lacking such an electron-withdrawing substituent gave vinylic epoxides in high yield e.g. equation 8. In the... 

Semi-stabilized arsonium ylides are intermediate in behaviour between stable and reactive ylides, and may provide alkenes and/or epoxides " °. In these cases factors such as the substituent groups on arsenic, and the nature of the solvent and of the base, may become important in determining the nature of the product this will be considered in more detail later (Section V.A.4). Small changes in the structure of the ylidic moiety may also have a marked effect for example, whereas triphenylarsonium jS-napththylmethylide reacts to give epoxide, the presence of a bromine atom at the adjacent a-position of the naphthalene ring results instead in the formation of alkenes . ... 

The first report of such effects was in a study of the reactions of a series of tris(p-substituted phenyl)arsonium ylides with benzaldehyde all these ylides gave epoxides in high yield save for the tris(p-dimethylamino) compound, which gave instead the trans-alkene L In further experiments replacement of a triphenylarsonium group by a tris(p-methoxyphenyl)arsonium group was found to have little effect on the ratio of products and inclusion of the arsenic atom in a strained ring also had no effect. ... 

A publication discussing the uses of reactive arsonium ylides for the stereospecific preparation of epoxides draws attention to the fact that arsonium salts are less readily prepared than phosphonium salts because of the poorer nucleophilicity of arsenic compared to phosphorus, and suggests methods for obtaining them. Primary salts were made from alkyl triflates, while a-branched salts were prepared from alkyldiphenylarsines, obtained from iodo compounds as, for example, in equation 23. Reaction of alkyl halides with arsines to form arsonium salts is also promoted by the presence of silver tetra-fluoroborate . 

Arsonium ylides were discovered near the turn of the century, but their reactions with carbonyl compounds did not become elucidated until the 1960s. In a broad sense, arsonium ylides are midway in chemical behavior between ylides of phosphorus and those of sulfur. Stabilized arsonium ylides react with carbonyl compounds to afford alkenes, whereas the unstabilized analogs give rise to epoxides. More subtly, the nature of the substituents on either the ylide arsenic or carbon atom can alter the course of the reaction the choice of solvent can exert a similar effect. ... 

The reactions of substituted arsonium ylides with ciubonyl compounds can be carried out with high stereoselectivity in favor of rranr-disubstituted epoxides (equation 14). Equatorial attack is observed for addition to 4-r-butylcyclohexanone. Good stereoselectivity (S9 l) was observed for the addition of triphenylarsonium methylide to some (A A(-dibenzyl)amino aldehydes at -78 °C in THF. Interestingly, the initial hydroxy tetraalkylarsonium adducts were isolated under these conditions, and had to be cyclized under the action of sodium hydride in a separate step. 

Another arsonium ylide reaction involves a notable transylidation reaction between a phosphorus and an arsenic ylide (Scheme 6). A useful arsenic ylide which provides a hydroxymethyl epoxide has been reported (equation IS) note the use of biphasic reaction conditions for ylide generation. 

Among the heavy main group elements arsenic has received the most attention. Arsonium ylides react with carbonyl compounds to yield either the alkenes or epoxides, depending upon the structure of the ylide and the reaction conditions. )espite their toxicity, arsenic compounds can be handled safely. 

A useful method for the direct epoxidation of carbonyl compounds involves reaction of an unstabilized arsonium ylide (10) with an aldehyde or ketone, analogous to the reactions of sulphur ylides. Unlike previous methods, the reaction of (10) to form (11) proceeds with a high degree of stereochemical control, and most aldehydes react cleanly giving frans-oxirans. Drawbacks to the method are (i) the toxicity of arsenic, and (ii) the fact that since PhaAs is... 

In Wittig-type reactions with aldehydes and ketones, arsonium ylides have been shown to give either epoxides or alkenes or mixtures thereof (Scheme 3.88) [140]. However, the semi-stabihzed yHde 457 can be directed onto either pathway by tuning the basicity of the solvent [141]. In pure TH F, the epoxide 459 was formed, whereas in THF/HMPA mixtures the conjugated diene 461 was obtained. This complete switch was observed for a variety of aldehydes and ketones. Rationalization lies in the assumption of zwitterionic intermediates 458 and 460, which react via different conformations. Thus, the anti-conformer 458 is reactive in unipolar solvents, presumably via aggregate formation to give the epoxide, whereas in the presence of HMPA the monomeric species 460 is formed, which undergoes syn-elimination. 

With HMPA, Wittig reactions that give ( )-alkenes were also observed (eq 18), as was the directed selectivity of a semista-bilized arsonium ylide towards carbonyl compounds. The arsenic ylide was generated from LDA in THF or THF/HMPA solution to give exclusively epoxide (eq 19) or diene (eq 20), respectively. ... 

Such ylides are unstable and react with carbonyl compounds to give both the Wittig product (p. 545) as well as AsPh3 and an epoxide. However, this very reactivity is sometimes an advantage since As ylides often react with carbonyl compounds that are unresponsive to P ylides. Substituted quaternary arsonium compounds are also a useful source of heterocyclic organoarsanes, e.g. thermolysis of 4-(1,7-dibromoheptyl)trimethylarsonium bromide to l-arsabicyclo[3.3.0]octane ... 

Urns-Epoxides. This unstable ylide (1), when generated as formulated above, reacts with an aliphatic aldehyde at —78° to give a fram-epoxide with almost complete stereoselectivity. The stereochemical selectivity is markedly dependent on the base and also on the counterion of the arsonium salt. Optimum selectivity for the trans-epoxide is obtained with conditions similar to those that induce cis-olefination in Wittig reactions.2 Stereoselection is not so high with aromatic aldehydes. The reagent also reacts with ketones to form trisubstituted epoxides. 

The nature of the arsonium substituents also influences the course of the reaction. Gosney et al. (33) studied the reaction between arsonium salts of type 50 and benzaldehyde in THF using -butyllithium to generate the ylide. The results, summarized in Table IX, clearly show that electron-donating substituents at the arsenic atom promote the formation of al-kenes. At one extreme, the reaction of 0) gives a notable yield of stilbene almost to the exclusion of stilbene oxide, whereas at the other, the reaction of (a) yields predominantly stilbene oxide. Table IX shows that electron-donating substituents at arsenic increase the ratio of alkene to epoxide. 

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