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.
Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
Lydia J
LJ
Rono
Hatice G
HG
Yayla
David Y
DY
Wang
Michael F
MF
Armstrong
Robert R
RR
Knowles