Enantioselective synthesis of 3-substituted dihydrobenzofurans through iridium-catalyzed intramolecular hydroarylation

Intramolecular hydroarylation via C-H activation is one of the most powerful methods to synthesize carbo- and heterocyclic compounds, whereas we still have room for developing a highly enantioselective variant of the reaction. Here we describe Ir-catalyzed enantioselective intramolecular hydroarylation of m-allyloxyphenyl ketones. The enantioselective cyclization was efficiently catalyzed by a cationic iridium complex coordinated with a conventional chiral bisphosphine ligand to give benzofurans in high yields with high enantioselectivity. A carbonyl group of ketones functioned as an effective directing group for the C-H activation. In terms of synthetic utility, we also achieved one-pot synthesis of chiral 3-substituted dihydrobenzofurans from readily available allylic carbonates and m-hydroxyacetophenones via sequential Pd-catalyzed allylic substitution and Ir-catalyzed intramolecular hydroarylation.

Automated summary

This study describes a highly enantioselective intramolecular hydroarylation reaction using C-H activation, catalyzed by an iridium catalyst and a chiral bisphosphine ligand. The carbonyl group of ketones serves as an effective directing group, allowing for efficient synthesis of chiral 3-substituted dihydrobenzofurans in high yields and enantioselectivity from readily available starting materials. The reaction showcases the potential for developing a more efficient and selective variant of the reaction.