Highly diastereoselective Michael addition to optically active trifluoromethylated alpha,beta-unsaturated sulfonamides based on their hinge-like conformation

Conformational analysis of alpha,beta-unsaturated sulfonamide based on ab initio calculation predicted a binge-like molecular shape of ground slate conformation. Referring to the result, three optically active trifluoromethylated sulfonamides 2a-c were designed and prepared from optically active pyrrolidines 1a-c as a chiral auxiliary. Michael additions to 2a-c with acetophenone/DA and dimethyl malonate/NaH gave the adducts with various diastereoselectivities. The most diastereoselective olefin 2c with C-2-symmetric chiral auxiliary was utilized as Michael acceptor to give >98 % de in the reaction with several selected nucleophiles. Copyright (C) 1996 Elsevier Science Ltd