Visible-light-mediated catalytic asymmetric synthesis of a-amino esters via free carbene insertion into N-H bond

A method that facilitates the construction of valuable chiral products exploiting simple high energy inter-mediates in an atom-and sustainable fashion could prove highly enabling for asymmetric synthesis. Free carbenes are one kind of such high energy intermediates and their utilization in catalytic asymmetric reactions is still elusive, due to the existence of severe racemic background reaction. In our pursuit to develop catalytic asymmetric N-H insertion reaction of free carbene, a general chiral Bronsted acid -cat-alyzed enantioselective protonation of the in situ generated ammonium ylide was discovered under vis-ible-light irradiation of diazo compound in the presence of arylamine, furnishing the desired a-amino esters with moderate to high enantioselectivity and yield. More importantly, it was found there is a remarkable correlation between the enantioselectivity of product and substituent electronic parameter (rpara) of substrates. This work not only demonstrates chiral phosphoric acid catalysis is compatible with free carbene insertion reactions without disturbing deactivation O-H insertion side reactions, but also indicates the pKa of arylamine is also a significant parameter for turning the enantioselectivity of the reaction. The method disclosed herein is expected to bring new insights into the use of free carbene in the catalytic asymmetric reactions under metal free conditions.CO 2023 Elsevier Ltd. All rights reserved.

Automated summary

This study discovered a method that utilizes high energy intermediates to construct valuable chiral products. By catalytic asymmetric protonation of in situ generated ammonium ylide using chiral Bronsted acid under visible-light irradiation, the desired α-amino esters were obtained with moderate to high enantioselectivity and yield. This method not only demonstrates the compatibility of chiral phosphoric acid catalysis with free carbene insertion reactions, but also indicates the significance of arylamine's pKa value in tuning the enantioselectivity of the reaction.