Carbene-Catalyzed Intermolecular Dehydrogenative Coupling of Aldehydes with C(sp(3))-H Bonds

The development of catalyst-controlled methods for direct functionalization of two distinct C-H bonds represents an appealing approach for C-C formations in synthetic chemistry. Herein, we describe an organocatalytic approach for straightforward acylation of C(sp(3))-H bonds employing readily available aldehyde as acyl source involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp(3))-H bonds. The developed method affords a broad range of ketones under mild conditions. Mechanistically, simple ortho-cyanoiodobenzene is essential in the oxidative radical N-heterocyclic carbene catalysis to give a ketyl radical and C(sp(3)) radical through a rarely explored intermolecular hydrogen atom transfer pathway, rendering the acylative C-C formations in high efficiency under a metal- and light-free catalytic conditions. Moreover, the prepared products show promising anti-bacterial activities that shall encourage further investigations on novel agrochemical development.

Automated summary

The development of catalyst-controlled methods for direct functionalization of two distinct C-H bonds is an appealing approach for C-C formations in synthetic chemistry. This article describes an organocatalytic approach using readily available aldehyde as acyl source, which allows for the straightforward acylation of C(sp(3))-H bonds involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp(3))-H bonds. The developed method provides a wide range of ketones under mild conditions.