Nickel-Catalyzed Enantioconvergent Carboxylation Enabled by a Chiral 2,2';-Bipyridine Ligand

In contrast to previous approaches to chiral alpha-aryl carboxylic acids that based on reactions using hazardous gases, pressurized setup and mostly noble metal catalysts, in this work, a nickel-catalyzed general, efficient and highly enantioselective carboxylation reaction of racemic benzylic (pseudo)halides under mild conditions using atmospheric CO2 has been developed. A unique chiral 2,2'-bipyridine ligand named Me-SBpy featuring compact polycyclic skeleton enabled both high reactivity and stereoselectivity. The utility of this method has been demonstrated by synthesis of various chiral alpha-aryl carboxylic acids (30 examples, up to 95 % yield and 99 : 1 er), including profen family anti-inflammatory drugs and transformations using the acids as key intermediates. Based on mechanistic experimental results, a plausible catalytic cycle involving Ni-complex/radical equilibrium and Lewis acid-assisted CO2 activation has been proposed.

Automated summary

A nickel-catalyzed general, efficient, and highly enantioselective carboxylation reaction of racemic benzylic (pseudo)halides has been developed, utilizing atmospheric CO2 under mild conditions. A unique chiral 2,2'-bipyridine ligand enabled both high reactivity and stereoselectivity.