A Convenient New Synthesis of 3‐Substituted β‐Lactams Formally Derived from 1‐(Aminomethyl)cyclopropanecarboxylic Acids

Abstract 1,3‐Dipolar cycloaddition of N‐benzyl‐C‐(methoxycarbonyl)nitrone (3a), N‐benzyl‐C‐phenylnitrone (3b), N‐benzyl‐C‐cyanonitrone (3c), N‐(p‐methoxybenzyl)‐C‐cyanonitrone (3d), N‐phenyl‐ (3e) and N‐(2‐pyridyl)‐C‐methylnitrones (3f) to bicyclopropylidene (2) gave the corresponding cycloadducts 5a−f in 100, 95, 94, 100, 93 and 71% yields, respectively. Treatment of these bisspirocyclopropanated isoxazolidines with trifluoroacetic acid in acetonitrile furnished the corresponding 3‐spirocyclopropanated β‐lactams 7a−f in 78, 75, 75, 94, 96 and 96% yields, respectively. The structures of the cycloadduct 5b and of the β‐lactam 9a were proved by X‐ray crystal structure analyses. Thus, this new method furnishes compounds with a 5‐azaspiro[2.3]hexan‐4‐one skeleton in 68−94% overall yield in two simple steps. β‐Lactams 7a, 7b, and 7d were converted into their N‐acyl derivatives 9a, 9b, 9d and 11 in 44, 28, 39 and 78% yields, respectively. Heating of the β‐lactams 9b and 11 with tert‐butyl glycinate (12) or with tert‐butyl (S)‐phenylalaninate (14) in DMF led to ring‐opening of the β‐lactam moiety to give β‐dipeptides 15, 16 and 17 in 61, 84 and 79% yields, respectively, while β‐lactam 9a gave the amide 13 (51% yield). β‐Lactams 7e and 7f turned out not to be transformable into such peptide products (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)