Favorskii Rearrangements of α-Halogenated Acetylcycloalkanes. 4. Stereochemistry of Cyclopropanonic Rearrangements and the Influence of Steric Factors on the Competing Formation of α-Hydroxy Ketones

Article abstract of DOI:10.1021/jo00160a004

It is shown that the marked stereoselectivity, in favor of 17α-methylated etio acid derivatives, of Favorskii rearrangements in protic and polar media of 17-brominated 20-keto steroids - somewhat diminished by a bulky 12α-substituent, such as an acetoxy group - is due, to an appreciable extent, to the influence of the 18-methyl group.Thus, the rearrangement of 17-bromo-3β-acetoxy-18-nor-5α-pregnan-20-one, which was synthesized from 3β-acetoxy-5α-androstan-17-one, proceeds with potassium bicarbonate in aqueous methanol much less stereoselectively than analogous rearrang ements of 13-methylated 17-bromo 20-ketones, and in its reaction with potassium methoxide in absolute methanol the yield of the 17β-methyl 17α-etio ester even exceeds that of the 17α-methylated rearrangement product, in contradistinction to the results of equivalent reactions of 13-methylated substrates.It is also shown that in the absence of the 18-methyl group a 17β-hydroxy 20-ketonic substitution product and related adducts are obtained in high proportion, and it is concluded that the quasi-absence of such products in analogous reactions of 13-methylated 17-bromo 20-keto steroids is essentially due to the steric impediment exerted by this group to the formation of intermediate epoxy ethers.The results presented agree with the hypothesis of a competition between concerted and nonconcerted cyclopropanone formations from α-halo enolates, in part dependent on the polarity and protonicity of the medium, or possibly with that of gradients of mechanisms, and they support the intermediacy of epoxy ethers in the formation of α-hydroxy ketones as side products of Favorskii rearrangements.