Sulfenylation and Halogenation of Di-and Trianions Derived from Substituted Glutarimides

Abstract

Abstract In a program designed to synthesize and evaluate glutethimide derivatives 1 for antiprogestational activity1 we required a general method for introducing a variety of substituents at C-5. Traditional methods for functionalizing an α carbon of glutarimide derivatives involve (1) cyclization of an appropriately substituted acyclic precursor2, (2) imide bromination followed by SN2 delivery of the desired substituent3, or (3) generation of the dianion of the imide with an alkali amide in liquid ammonia and reaction with an electrophile4. The utilization of an intermediate dianion was prompted, in large measure, by limitations imposed by the first two methods, i.e., the large number of synthetic operations re-quired to prepare a series of highly functionalized acyclic precursors and the paucity of nucleophiles capable of displacing bromide without concomitant side reactions.