Rh-Catalyzed Enantioselective Synthesis of Acyclic Quaternary Carbons via Carbene Insertion

Abstract

Herein, the construction of acyclic quaternary carbon chiral centers through carbene insertions in a chiral metal carbene mechanism is reported. Carbene insertion products can be obtained with high chemical selectivity, regioselectivity, Z/E selectivity, and enantioselectivity using α-diazo esters and enone-hydrazones under the conditions of a chiral dirhodium catalyst. The mechanism verification experiments demonstrate that the benzene ring, originating from the enone-hydrazones, can shield the O and NH coordination atoms of the enone-hydrazones. This shielding effect is crucial for the asymmetric C–C bond insertion reaction catalyzed by a chiral metal carbene complex derived from a chiral dirhodium. Additionally, the results of the controlled experiments indicate that achieving the asymmetric version of the traditional C–C insertion substrate is challenging. This challenge arises from the coordination of the substrate with the Rh1 site of the chiral dirhodium catalyst, which subsequently leads to carbene precursor activation occurring at the Rh2 site, resulting in poor stereoselectivity.