Strain-Driven Dyotropic Rearrangement: A Unified Ring-Expansion Approach to alpha-Methylene-gamma-butyrolactones

An unprecedented strain-driven dyotropic rearrangement of alpha-methylene-beta-lactones has been realized, which enables the efficient access of a wide range of alpha-methylene-gamma-butyrolactones displaying remarkable structural diversity. Several appealing features of the reaction, including excellent efficiency, high stereospecificity, predictable chemoselectivity and broad substrate scope, render it a powerful tool for the synthesis of MBL-containing molecules of either natural or synthetic origin. Both experimental and computational evidences suggest that the new variant of dyotropic rearrangements proceed in a dualistic pattern: while an asynchronous concerted mechanism most likely accounts for the reactions featuring hydrogen migration, a stepwise process involving a phenonium ion intermediate is favored in the cases of aryl migration. The great synthetic potential of the title reaction is exemplified by its application to the efficient construction of several natural products and relevant scaffolds.