Development of Pseudo-<i>C</i>₂-symmetric Chiral Binaphthyl Monocarboxylic Acids for Enantioselective C(sp³)–H Functionalization Reactions under Rh(III) Catalysis

Abstract

Enantioselective C(sp3)–H functionalization reactions using high-valent group 9 metal catalysts with cyclopentadienyl ligands have been achieved by the introduction of appropriate chiral carboxylic acids. However, the diversity of the chiral carboxylic acids, as well as that of the applicable substrate structures remains limited. Herein, we report pseudo-C2-symmetric tunable chiral carboxylic acids with a binaphthyl backbone and their application to enantioselective C(sp3)–H amidation reactions of 2-alkylpyridines and related heteroaromatic substrates. The fixed cyclic structure and pseudo-C2-symmetry of the developed chiral carboxylic acids would reduce the conformational flexibility and ambiguity. The combination of an optimal chiral carboxylic acid and a sterically hindered rhodium catalyst (Cp*tBuRhIII) exhibited high enantioselectivity (up to 96:4 er).