Title: Catalytic Reductive Amination and Tandem Amination–Alkylation of Esters Enabled by a Cationic Iridium Complex

Authors: Guangsheng Lu+, Zhonglei Ruan+, Yanwang+, Jinfang Lü, Jianliang Ye, Peiqiang Huang*

Abstract: Reported herein is a convenient and efficient method forone-pot, catalytic reductive amination, as well as the first multi-component tandem reductive amination - functionalization of bench-stable and readily available common carboxylic esters. This methodis based on the cationic [Ir(COD)2]BArF-catalyzed chemoselectivehydrosilylation of esters, followed by one-pot acid-mediated aminationand nucleophilic addition. The reaction was conducted under mildconditions at a very low catalyst loading (0.1 mol% of Ir), which couldbe further reduced to 0.001 mol%, as demonstrated by a reaction ata 15 g scale. The method is highly versatile, allowing the use of esterswith or without α-protons for the N-mono-alkylation of primary andsecondary amines to produce diverse secondary and tertiary amines,as well as α-branched/functionalized amines. The method is highlychemoselective and tolerates a variety of functional groups such asbromo, trifluoromethyl, ester, and cyano groups. The value of themethod was demonstrated by the one-step catalytic synthesis of twobio-relevant N-mono-methyl α-amino esters and the antiparkinsonianagent piribedil, as well as by the use of two shorter chain triglyceridesas alkylating feedstock.

Full-Link: https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202422742