Rapid syntheses of some indole alkaloids of the calabar bean

Abstract

A rapid, efficient route to 3,3-disubstituted oxindoles from o-iodo anilines has been developed. It involves the cyclisation of the corresponding fumarate amides 4 and 15 with butyllithium at –100°C in the presence of an excess of trimethylchlorosilane. An X-ray crystal structure of 4 suggests that the speed and efficiency of this intramolecular Michael addition is dependent on the conformation adopted by 4 which is particularly suitable for the reaction. This method has been applied to the synthesis of the alkaloids physovenine, physostigmine and esermethole in very high overall yields.