Enantioselective synthesis of strobamine and its analogues
(2S,5S,8R)-Strobamine (+)-1a was synthesized by adding cinnamoyl cyanide 6a to tropinone 3 lithium enolate generated by treatment of (S,S')-?,?-dimethyldibenzylamide with butyl lithium in the presence of lithium chloride to give (–)-chalcostrobamine (–)-7a, which yielded a one-to-one mixture of (+)-1a and its C-2 epimer (–)-2a on treatment with 2N sulfuric acid. Compounds (+)-1a and (–)-2a could be separated by column chromatography. (–)-Strobamine (–)-1a and (+)-2a were synthesized by a similar set of reactions using the tropinone 3 lithium enolate generated with butyl lithium in the presence of (R,R')-?,?'-dimethyldibenzylamide and lithium chloride. (+)- and (–)-p-Methylstrobamine (+)- and (–)-1b and (+)- and (–)-epi-p-methylstrobamine (+)- and (–)-2b were synthesized by a similar procedure. The absolute configuration of (+)-epi-p-methylstrobamine (+)-2b was determined by X-ray analysis to have the (2S,5R,8S) configuration.