Stereospecificity Favorskii reaction

In a more polar solvent, Favorskii reactions cease to be stereospecific, and presumably take place by ionisation of the chloride to give the same cation from each diastereoisomer. Whether the reaction takes place by way of the cation or with concerted loss of the chloride ion, this reaction presented a serious puzzle before its pericyclic nature was recognised. The a overlap of the p orbital on C-2 of the enolate with the p orbital at the other end of the allyl cation 6.340 or with the orbital of the C—Cl bond 6.341 looked forbiddingly unlikely—it is 3-endo-trig at C-2. It is made possible by its pericyclic nature, where the tilt of the orbitals can begin to sense the development of overlap. The torquoselectivity in the development of overlap 6.341, however improbable it looks, corresponds to inversion of configuration at the carbon atom from which the chloride departs. 

Favorskii rearrangements, and other examples are known in the steroid nucleus (see below). Highly polar solvents (methanol or aqueous methanol) were originally used for these reactions the bromoketones may undergo dehydrobromination or substitution reactions in basic media of low polarity, such as pyridine or KOAc/HOAc. Recent work, however, has shown that sodium methoxide in aprotic solvents e.g. 1,2-dimethoxy-ethane) can be used, and tlxat the stereospecificity of various Favorskii reactions using simple alicyclic and aliphatic compounds is markedly dependent upon the nature of the solvent [301],... 

The reverse reaction of this general class—an allyl cation giving a cyclopropyl cation—is found in Favorskii rearrangements. The diastereoisomeric Q-chloro enolates 6.334 and 6.337 give the cyclopropanones 6.335 and 6.338, respectively. Thus the reaction is stereospecific, at least in a nonpolar solvent. Evidently the allyl cation is not formed, otherwise the two chlorides... 

The reaction of a polyhalo ketone with base (equation 3) was described several years before Favorskii described a similar rearrangement (equation 4). Simple a,a- and a,a -dihalo ketones yield the same product (Scheme 14), so dibromination can be followed by Favorskii rearrangement without purification. These rearrangements are usually stereospecific, though subsequent cis to trans isomerization, under the influence of base, often obscures this feature. Various explanations have been provided for this stereospecificity, but the one due to Rappe (illustrated in Scheme 15) seems most plausible. ... 

A noteworthy example of an unexpected result in this area is the cyanation of l-chloro-3-phenyl-propan-2-one (15) with sodium or potassium cyanide in aqueous acetone which yielded the condensation product 16 in 55% yield.It is proposed that the reaction occurs via a Favorskii-type 1,3-dehydrochlorination, followed by trapping of the intermediate cyclopropanone 18 by cyanide to give cyanohydrin 19, which is not isolable. Instead, it adds across the intermediate cyclopropanone 18 to give adduct 20, which opens in the so-called normal way to afford the most stable carbanion 21, the benzylic carbanion. On protonation, the final cyclopropanecar-bonitrile 16 is formed and isolated as one stereoisomer, resulting from stereospecific addition of cyanide to the intermediate cyclopropanone. As expected, the isomeric 1-chloro-l-phenyl-propan-2-one (17) reacted in similar manner with aqueous cyanide to afford adduct 16, albeit in a lower yield. 

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