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

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 S_N2 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 electrophile^4. 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.