Studies on enolate chemistry of 8-thiabicyclo[3.2.1]- octan-3-one: enantioselective deprotonation and synthesis of sulfur analogs of tropane alkaloids

Abstract

Enantioselective deprotonation of 8-thiabicyclo[3.2.1]octan-3-one (1) with chiral lithium amides, followed by reactions with electrophiles affords sulfur analogs of tropane alkaloids of pyranotropane family. Thus, deprotonation of 1 with (S)-N-(diphenyl)methyl-1-phenylethylamine (11d), followed by the reaction of the resulting nonracemic enolate with benzaldehyde gives the corresponding aldol product as one diastereoisomer (exo, threo) and in high enanatiomeric purity (95% ee). Trimethylsilyl chloride, acetic anhydride, and acyl cyanides react readily with the lithium enolate to give the corresponding derivatives of 1, however common alkylating agents fail to provide C-alkylated products. The reaction with acyl cyanides derived from α,β-unsaturated carboxylic acids (e.g., cinnamoyl cyanide) can be utilized in synthesis of thia-analogs of tropane alkaloids physoperuvine and isobellendine (13, 15).Key words: enantioselective deprotonation, tropane alkaloids.