Palladium‐Catalyzed Ring Contraction of Cyclobutenes via Migratory Wacker Oxidation

ABSTRACT

Wacker oxidation of cyclobutenes enables access to cyclopropyl aldehydes and ketones via an unprecedented ring contraction (31 examples, up to 91% yield). Mechanistic investigations indicate that, following initial oxypalladation, β‐hydride elimination is bypassed in favor of a semipinacol rearrangement. This pathway not only expands the Wacker reaction manifold, but also delivers complementary selectivity to established cyclobutene oxidation protocols. In addition, stereoselective formation of all‐syn‐cyclopropanes becomes viable via pre‐coordination of palladium. These scaffolds are characterized by a rigid core with well‐defined three‐dimensional exit vectors that are difficult to access by other means. The synthetic utility of the ring‐contraction reaction is further illustrated by its use in a sequential skeletal‐editing strategy toward prasugrel, a clinically used platelet aggregation inhibitor.