Micellar Catalysis Enables Asymmetric Transfer Hydrogenation of Hydrolytically Unstable Acyclic Imines in Water

Abstract

Chiral amines are essential structural motifs in pharmaceuticals, fine chemicals, and bioactive natural products. Asymmetric transfer hydrogenation (ATH) of imines represents one of the most straightforward approaches to chiral amine synthesis, yet aqueous ATH of non-activated acyclic imines remains a longstanding challenge due to the inherent hydrolytic lability of these substrates. Herein, we successfully achieve the aqueous asymmetric transfer hydrogenation of non-activated acyclic imines via a micellar catalysis strategy, employing an N,O-chelated half-sandwich iridium(III) complex as the chiral catalyst. The anionic surfactant sodium dodecyl sulfate (SDS) self-assembles into micelles in aqueous media, whose hydrophobic core encapsulates both the hydrolytically labile imine substrates and lipophilic metal catalyst. This confined microenvironment effectively isolates acyclic imines from the bulk aqueous phase to suppress the hydrolysis side reaction, while enriching reactants to improve mass transfer efficiency, and also exerts a positive regulatory effect on the stereochemical control of the transformation. After systematic optimization, this protocol has broad substrate scope, affording over 40 chiral amines in good to excellent yields with up to 98% enantiomeric excess (ee). With micellar catalysis suppressing substrate hydrolysis in water, this work provides an efficient green route to chiral amines and expands the scope of aqueous asymmetric transfer hydrogenation.