Synthesis of Strained Tricyclic β‐Lactams by Intramolecular [2+2] Cycloaddition Reactions of 2‐Azetidinone‐Tethered Enallenols: Control of Regioselectivity by Selective Alkene Substitution

Abstract

A convenient metal-free methodology for the preparation of structurally novel, strained tricyclic beta-lactams containing a cyclobutane ring has been developed. The first examples accounting for the intramolecular [2+2] cycloaddition reactions in beta-lactams have been achieved by the thermolysis of 2-azetidinone-tethered enallenols, which have been prepared in aqueous media by regio- and diastereoselective indium-mediated carbonyl allenylation of 4-oxoazetidine-2-carbaldehydes. Notably, the regioselectivity of the cycloaddition can be tuned in the allene component just by a subtle variation in the substitution pattern of the alkene component.