Ag(I)-Catalyzed Tandem Cyclization–Cycloaddition–Isomerization Reaction of 2-Alkynylbenzaldoxime with Bicyclobutane: A Route to Multiply Substituted Cyclobutanols

Abstract

Multiply substituted cyclobutanols are pivotal synthetic intermediates for constructing complex molecular architectures via ring-opening strategies. The development of efficient synthetic methods for these valuable building blocks has garnered significant interest in the chemical community. In this work, we have described a novel silver(I)-catalyzed tandem cyclization–cycloaddition–isomerization sequence with bicyclobutanes and 2-alkynylbenzaldoximes, which offered an effective route to multiply substituted cyclobutanols. This protocol features mild conditions, remarkable stereospecificity, a broad substrate scope, and excellent functional group tolerance. In addition, application potential of this reaction was readily proven by its high efficiency in reactants bearing biological moieties and scale-up experiments.