Enantioselective Photoredox Catalysis Enabled by Proton-Coupled Electron Transfer: Development of an Asymmetric Aza-Pinacol Cyclization

The first highly
enantioselective catalytic protocol for the reductive
coupling of ketones and hydrazones is reported. These reactions proceed
through neutral ketyl radical intermediates generated via a concerted
proton-coupled electron transfer (PCET) event jointly mediated by
a chiral phosphoric acid catalyst and the photoredox catalyst Ir­(ppy)2(dtbpy)­PF6. Remarkably, these neutral ketyl radicals
appear to remain H-bonded to the chiral conjugate base of the Brønsted
acid during the course of a subsequent C–C bond-forming step,
furnishing syn 1,2-amino alcohol derivatives with
excellent levels of diastereo- and enantioselectivity. This work provides
the first demonstration of the feasibility and potential benefits
of concerted PCET activation in asymmetric catalysis.