Asymmetric construction of two 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 asymmetric construction of two contiguous stereocenters by the conjugate addition of thiols to alpha,beta-unsaturated imides possessing Evans's chiral auxiliary. Addition reactions of thiophenol to chiral E- and Z-2-methylcrotonyl imides 4 proceeded with high diastereoface selectivities. Diastereoselectivities were discussed when E- and Z-imides 4 and 5 were used as the substrates. A successful application was demonstrated by the formal synthesis of a clinically useful cardiac drug, (+)-diltiazem. (C) 1997, Elsevier Science Ltd.