ASYMMETRIC CONSTRUCTION OF 2 CONTIGUOUS STEREOCENTERS BY DIASTEREOFACE DIFFERENTIATING ADDITION-REACTION OF THIOLS TO CHIRAL IMIDES - FORMAL SYNTHESIS OF (-DILTIAZEM())

A high degree of diastereoselectivity has been achieved on the asymmet ric construction of two contiguous stereocenters by the conjugate addi tion of thiols to alpha,beta-unsaturated imides possessing Evans's chi ral auxiliary. Addition reactions of thiophenol to chiral E- and Z-2-m ethylcrotonyl imides 4 proceeded with high diastereoface selectivities . Diastereoselectivities were discussed when E- and Z-imides 4 and 5 w ere used as the substrates. A successful application was demonstrated by the formal synthesis of a clinically useful cardiac drug, (+)-dilti azem. (C) 1997, Elsevier Science Ltd.