Asymmetric Transfer Hydrogenative Amination of Benzylic Ketones Catalyzed by CpIr(III) Complexes Bearing a Chiral N‑(2-Picolyl)sulfonamidato Ligand

• Published in: Journal of organic chemistry 2022-07, Vol.87 (13), p.8458-8468
• Main Authors: Kawada, Takuma, Yabushita, Kenya, Yasuda, Toshihisa, Ohta, Takeshi, Yajima, Takaaki, Tanaka, Kouichi, Utsumi, Noriyuki, Watanabe, Masahito, Murata, Kunihiko, Kayaki, Yoshihito, Kuwata, Shigeki, Katayama, Takeaki
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c00580

A convenient asymmetric reductive amination of benzylic ketones (α-arylated ketones) catalyzed by newly designed Cp*Ir complexes bearing a chiral N-(2-picolyl)­sulfonamidato ligand was developed. Using readily available β-amino alcohols as chiral aminating agents, a range of benzo-fused and acyclic ketones were successfully reduced with formic acid in methanol at 40 °C to afford amines with favorable chemo- and diastereoselectivities. The amino alcohol-derived chiral auxiliary was easily removed by mild periodic oxidants, leading to optically active primary β-arylamines without erosion of the optical purity (up to 97% ee). The excellent catalytic performance was retained even upon lowering the amount of catalyst to a substrate/catalyst (S/C) ratio of 20,000, and the amination could be performed on a large scale exceeding 100 g. The precise hydride transfer to iminium species generated from the ketonic substrate and the chiral amine counterpart was suggested by the mechanistic studies on stoichiometric reactions of isolable hydridoiridium complexes and model intermediates such as N,O-acetal, enamine, and iminium compounds.