Enantioselective photoredox catalysis enabled by proton-coupled electron transfer: development of an asymmetric aza-pinacol cyclization

J Am Chem Soc. 2013 Nov 27;135(47):17735-8. doi: 10.1021/ja4100595. Epub 2013 Nov 13.


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.