Editing Tetrasubstituted Carbon: Dual C–O Bond Functionalization of Tertiary Alcohols Enabled by Palladium-Based Dyotropic Rearrangement

Abstract

Many elegant asymmetric syntheses of enantioenriched tertiary alcohols have been developed, and both the transition metal-catalyzed and the radical-based peripheral functionalization of tertiary alcohols have attracted intensive research interest in recent years. However, directly editing tetrasubstituted carbons remains challenging. Herein, we report a Pd-catalyzed migratory fluoroarylation reaction that converts tertiary alcohols to α-fluorinated tertiary alkyl ethers in good to excellent yields. An unprecedented 1,2-aryl/Pd IV dyotropic rearrangement along the C−O bond, integrated in a Pd II -catalyzed domino process, is key to the dual functionalization of both the hydroxyl group and the tetrasubstituted carbon. This reaction, which is compatible with a broad range of functional groups, generates a tertiary alkyl fluoride and an alkyl-aryl ether functional group with inversion of the absolute configuration at the tetrasubstituted stereocenter.

Quaternary Carbon Editing Enabled by Sequential Palladium Migration

“…Exploiting the Pd-based dyotropic rearrangement, − we have developed a palladium-catalyzed migrative carbofluorination of saturated amides enabled by the activation of both the C(sp 3 )–H and the C quaternary –C σ bonds (Scheme b) . In this transformation, the α-quaternary carbon of Weinreb amides is converted to α-tertiary fluoride with concurrent migration of an aryl or amido group from the α- to the β-carbon.…”