Syntheses of β-lactams by ring contraction of isothiazolidinones

Abstract

Several methods have been developed for the preparation of β-lactams from isothiazolidinones. Oxidation of 2-t-butyl-4,4-diphenyl- and 2,4,4-trimethyl-isothiazolidin-3-ones (4a) and (4b) with sulphuryl chloride afforded the 5-chloroisothiazolidinones (5a) and (5b), which were converted into 1-t-butyl-3,3-diphenyl- and 1,3,3-trimethyl-4-phenylthioazetidin-2-ones (6a) and (6b) by treatment with phenyl-lithium. Alternatively, reaction of the isothiazolidinones (4a) and (4b) with phenyl-lithium gave N-t-butyl-2,2-diphenyl- and N,2,2-trimethyl-3-phenylthiopropionamides (12a) and (12b), which were transformed into the p-lactams (6a) and (6b) by halogenation at C-3, followed by treatment with potassium amide. These are examples of methods used to prepare β-lactams from isothiazolidinones. The versatility of these reactions and their relevance to penicillin biosynthesis is discussed.