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

Abstract

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 α‐protons for the N‐mono‐alkylation of primary and secondary amines to produce diverse secondary and tertiary amines, as well as α‐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 α‐amino esters and the antiparkinsonian agent piribedil, as well as by the use of two shorter chain triglycerides as alkylating feedstock.