Stereospecificity Favorskii rearrangement

Much effort this year has been expended on chrysanthemic acid syntheses. Aratani et al. have extended earlier work on asymmetric synthesis (Vol. 6, p. 21) by decomposing various alkyl diazoacetates in 2,5-dimethylhexa-2,4-diene in the presence of chiral copper complexes to yield up to 92% of rrans-chrysanthemic acid in 88% dextrorotatory enantiomeric excess. Mitra has used ozonolysis of (+)-a-pinene to obtain, stereospecifically, the bromo-ketone (104) which undergoes Favorskii rearrangement to yield the anticipated ester (105) from which (+)-trans-chrysanthemic acid is readily obtained a second paper reports another route from (+)-car-3-ene initially to methyl (—)-c/s-chrysanthemate or to (—)-dihydro-chrysanthemolactone (106), both of which are convertible into (+)-rra s-chrysan-... 

A previous Organia Syntheses procedure for the preparation of isocrotonic acid involves the stereospecific Favorskii rearrangement of l,3-dibromo-2-butanone.6 However, the procedure is rather laborious and, in our hands, gives only a modest overall yield of acid. Isocrotonic acid has also been prepared by carbonation of cis-propenyllithium and by sodium amalgam... 

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... 

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 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. ... 

Favorskii rearrangements have been reported with alicyclic and heterocyclic bromocycloalkanones containing 4-13 (but not S) atoms in the rings. The important mechanistic studies with 2-bromocyclobu-tanone have already been mentioned (Scheme 10), and Scheme 23 contains a summary of other results obtained by Conia and coworkers.Of particular note is the fact that the rearrangement will even proceed with water as reagent, and that the stereospecificity observed is consistent with a mechanism involving (as expected) inversion of configuration at the cartmn center initially attached to the bromine atom. 

Scheme 7tlQ Stereospecificity of the quasi-Favorskii rearrangement.

The Favorskii rearrangement has been reviewed and a key step in a synthesis of ( )-communiol E was found to involve stereospecific oxy-Favorskii rearrangement to form branched cfx-fused bicyclic ethers with both tertiary and quaternary centres (Scheme 91). ... 

Stereospecific Favorskii rearrangement czs-a,/ -EthyIenecarboxylic acid esters from dibromomethyl ketones... 

Zinc-promoted debromination of PhjCHBrCOCHjBr results in a Favorskii product under typical Reformatsky conditions, and a cyclopropanone is presumably implicated. Favorskii rearrangements of (402 X = O) and corresponding 1,3-dichloro-compounds are explicable in terms of stereospecific disrotatory closure of the initially generated zwitterions (Scheme 61). Generated in this way, (403 X = O)... 

Diastereoselective Favorskii ring contractionBicyclic a-chloro-8-lactams can undergo highly diastereoselective ring contraction to proline derivatives when treated with base, preferably barium hydroxide in aqueous solution. Thus 1 is converted into 2 and 3 in the ratio 9 1. The ring contraction of 4 to 5 is stereospecific. In contrast, rearrangement... 

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