Enantioselective Acylation of Benzylic C(sp3)-H Bond Enabled by a Cooperative Photoredox and N-Heterocyclic Carbene Catalysis.

Journal: Angewandte Chemie (International Ed. In English)
Published:
Abstract

Organocatalyzed direct and asymmetric functionalization of benzylic C(sp3)─H bond is attractive yet challenging. Herein, we report the enantioselective acylation of benzylic C(sp3)─H bond via a cooperative photoredox and N-heterocyclic carbene (NHC) catalysis, affording the corresponding chiral α-aryl ketones in moderate to good yields with good to excellent enantioselectivities (up to 99:1 er). The rational design of novel NHCs guided by the initial evaluation of available catalysts and their application promotes the asymmetric transformation. Mechanistic experiments and density functional theory (DFT) calculations support the formation of benzyl radical and ketyl radical intermediates and rationalize the coupling of these radical species via open-shell singlet transition states to be the enantiodetermining step. This redox neutral protocol features mild conditions and is free of transition-metals (TMs) and pre-functionalized radical precursors.

Authors
Cao-bo Li, Xue-ning Li, Zhi-cheng Li, Jikun Li, Zhi-xiang Wang, Zhong-hua Gao, Song Ye