Cationic Iridium/Chiral Bisphosphine-Catalyzed Enantioselective Hydroacylation of Ketones

Tomohiko Shirai; Tomoya Iwasaki; Kazuya Kanemoto; Yasunori Yamamoto

doi:10.1002/asia.202000386

Cationic Iridium/Chiral Bisphosphine-Catalyzed Enantioselective Hydroacylation of Ketones

Chem Asian J. 2020 Jun 17;15(12):1858-1862. doi: 10.1002/asia.202000386. Epub 2020 May 27.

Authors

Tomohiko Shirai¹, Tomoya Iwasaki², Kazuya Kanemoto³, Yasunori Yamamoto⁴

Affiliations

¹ Department of Social Design Engineering, National Institute of Technology, Kochi College, 200-1 Monobe, Otsu, Nankoku, Kochi, 783-8508, Japan.
² Department of Materials Science and Engineering, National Institute of Technology, Kochi College, 200-1 Monobe otsu, Nankoku, Kochi, 783-8508, Japan.
³ Department of Applied Chemistry, Institute of Science and Engineering, Chuo University Kasuga 1-3-27, Bunkyo-ku, Tokyo, 112-8551, Japan.
⁴ Division of Applied Chemistry and Frontier Chemistry Center (FCC), Faculty of Engineering, Hokkaido University Kita 13 Nishi 8, Kita-ku, Sapporo, Hokkaido, 060-8628, Japan.

PMID: 32294313
DOI: 10.1002/asia.202000386

Abstract

A facile and convenient synthesis of the chiral phthalide framework catalyzed by cationic iridium was developed. The method utilized cationic iridium/bisphosphine-catalyzed asymmetric intramolecular carbonyl hydroacylation of 2-keto benzaldehydes to furnish the corresponding optically active phthalide products in good to excellent enantioselectivities (up to 98% ee). The mechanistic studies using a deuterium-labelled substrate suggested that the reaction involved an intramolecular carbonyl insertion mechanism to iridium hydride intermediate. In addition, we investigated the kinetic isotope effect (KIE) of intramolecular hydroacylation with deuterated substrate and determined that the C-H activation step is not included in the turnover-limiting step.

Keywords: C−H activation; cationic iridium; enantioselective; hydroacylation; ketone.

Grants and funding

JP19K15575/Society for the Promotion of Science