Regio- and Enantioselective Catalytic δ-C–H Amidation of Dioxazolones Enabled by Open-Shell Copper-Nitrenoid Transfer
Suhyeon Kim, Se Lin Song, Jianbo Zhang, Dongwook Kim, Sungwoo Hong, Sukbok Chang
Abstract
Controlling regio- and enantioselectivity in C–H functionalization reactions is of paramount importance due to their versatile synthetic utilities. Herein, we describe a new approach for the asymmetric δ-C(sp 3 )–H amidation catalysis of dioxazolones using a Cu(I) precursor with a chiral bisoxazoline ligand to access six-membered lactams with high to excellent regio- and enantioselectivity (up to >19:1 rr and >99:1 er). Combined experimental and computational mechanistic studies unveiled that the open-shell character of the postulated Cu-nitrenoids enables the regioselective hydrogen atom abstraction and subsequent enantio-determining radical rebound of the resulting carbon radical intermediates. The synthetic utility of this asymmetric cyclization was demonstrated in the diastereoselective introduction of additional functional groups into the chiral δ-lactam skeleton as well as in the rapid access to biorelevant azacyclic compounds.