The synthesis of (-)-stemoamide was achieved in 11 steps from 5-acetoxy-N-crotyl pyrrolidinone. A chiral N-acyl thiazolidinethione was employed in a stereoselective addition to a cyclic N-acyl iminium ion to install the required stereochemistry of carbon C9a. This iminium ion addition product was employed in a stereoselective MgBr2-catalyzed anti-aldol reaction to install the required stereochemistry of carbons C8 and C9. The X-ray crystal analysis of (-)-stemoamide confirmed the structure and the stereochemical outcome of these selective reactions.

[reaction: see text] Addition of the chlorotitanium enolate of N-acetyl 4-isopropyl-1,3-thiazolidine-2-thione to five-membered, N-substituted N-acyl iminium ions furnished the corresponding Mannich-type addition products with good diastereoselectivity and in good yields. The synthetic utility of the addition product 8 was demonstrated in a chemospecific anti-aldol reaction with cinnamaldehyde. By using this strategy, we constructed three contiguous chiral centers with high stereocontrol employing the same chiral auxiliary. X-Ray crystallographic analysis of addition product 2 and aldol product 14 revealed their absolute stereochemistry.