A new three-component cascade reaction to yield 3-spirocyclopropanated beta-lactams

Abstract

A one-pot three-component reaction for the direct conversion of certain alkylhydroxylamine hydrochlorides 8 (alkyl = benzyl, p-methoxybenzyl, benzhydryl, tert-butyl), formaldehyde (9) or an alkyl glyoxylate (10) and bicyclopropylidene (2) to furnish 3-spirocyclopropanated 2-azetidinones 7, 11 has been developed. Microwave heating of mixtures of the three components in the presence of sodium acetate in ethanol for 15-120 min furnished the products 7, 11 in 49-78% yield (7 examples). A new protocol for the oxidative deprotection of the 3-spirocyclopropanated methyl 1-(p-methoxybenzyl)-2-carboxylate 11b-Me provides the beta-lactam building block 17-Me in 90% yield, and the latter can be reprotected and activated with an N-tert-butoxycarbonyl (Boc) group in 82% yield. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006).