Construction of Azetidinols via tBuOK-Mediated Formal [3 + 1] Annulation of N-Formylimides and Seyferth-Gilbert Reagent.

The tBuOK-mediated protocol enables efficient access to a variety of substituted azetidinols from N-formylimides and Seyferth-Gilbert reagent through an unprecedented [3 + 1] tandem nucleophilic addition/anionic migration/cyclization/reduction process. The transformation proceeds under mild conditions, features a broad substrate scope, and exhibits excellent functional group tolerance including heteroaromatic scaffolds, alkenes, alkynes, ethers, and esters. Importantly, the protocol is readily scalable and applicable to the modification of complex drug molecules.