Catalytic Enantioselective Hydrogen Atom Abstraction Enables the Asymmetric Oxidation of Meso Diols.

Desymmetrization of meso diols is an important strategy for the synthesis of chiral oxygen-containing building blocks. Oxidative desymmetrization is an important subclass, but existing methods are often constrained by the need for activated alcohol substrates. We disclose a conceptually distinct strategy toward oxidative diol desymmetrization that is enabled by catalytic enantioselective hydrogen atom abstraction. Following single electron oxidation of a cinchona alkaloid-derived catalyst, enantiodetermining hydrogen atom abstraction generates a desymmetrized ketyl radical intermediate which reacts with either DIAD or O2 before in situ elimination to form valuable hydroxyketone products. A range of cyclic and acyclic meso diols are competent, defining the absolute configuration of up to four stereocenters in a single operation. As well as providing rapid access to complex hydroxyketones, this work emphasizes the broad synthetic potential of harnessing hydrogen atom abstraction in an enantioselective manner.