Catalytic Reductive Amination and Tandem Amination-Alkylation of Esters Enabled by a Cationic Iridium Complex

Reported herein is a convenient and efficient method for one-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 method is based on the cationic [Ir(COD)2]BArF-catalyzed chemoselective hydrosilylation of esters, followed by one-pot acid-mediated amination and nucleophilic addition. The reaction was conducted under mild conditions at a very low catalyst loading (0.1 mol % of Ir), which could be further reduced to 0.001 mol %, as demonstrated by a reaction at a 15 g scale. The method is highly versatile, allowing the use of esters with or without alpha-protons for the N-mono-alkylation of primary and secondary amines to produce diverse secondary and tertiary amines, as well as alpha-branched/functionalized amines. The method is highly chemoselective and tolerates a variety of functional groups such as bromo, trifluoromethyl, ester, and cyano groups. The value of the method was demonstrated by the one-step catalytic synthesis of two bio-relevant N-mono-methyl alpha-amino esters and the antiparkinsonian agent piribedil, as well as by the use of two shorter chain triglycerides as alkylating feedstock.