Construction of a thiourea-functionalized metallomacrocycle for the reductive amination of furfural under mild conditions

Abstract

A thiourea-functionalized metallomacrocycle was constructed as an efficient homogeneous catalyst for the reductive amination of furfural. Its weakly acidic cavity microenvironment with hydrogenbonding sites built from thiourea ligands enables the encapsulation of substrate molecules, thereby promoting the condensation of imines and their subsequent reduction.Reductive amination of biomass-derived carbonyl compounds constitutes a cornerstone transformation for the sustainable construction of C-N bonds, 1,2 enabling the direct and atom-economical synthesis of high-value amine intermediates that underpin modern pharmaceuticals, 3 agrochemicals, and functional polymers. 4 As a representative renewable platform chemical sourced from lignocellulosic biomass, furfural reductive amination has emerged as a pivotal route toward furfurylamine and its derivatives. Nevertheless, the catalytic reductive amination of furfural remains plagued by its reaction cascade (carbonyl-amine condensation to imine intermediates and subsequent reduction), sluggish kinetics under mild conditions and unselective side pathways (furfural auto-condensation, over-reduction) erode yield and selectivity 5 . More crucially, conventional hydrogen-bond-donating organic catalysts encounter dimers or multimers in homogeneous media, which results in self-quenching, shielding of active centres and ultimately leads to irreversible catalyst deactivation. 6 Natural enzymes (such as imine-reductases/transaminases) resolve such catalytic dilemmas through the exquisite architecture of enzyme active pockets, 7 which leverage confined microenvironments and directional noncovalent interactions to achieve precise substrate encapsulation, selective transition-state stabilization, and accelerated multistep reaction cascades. 8 Inspired by the enzymes, supramolecular catalysts capable of recapitulating the microenvironmental effects of biological binding pockets have attracted intensive interdisciplinary attention, 9-13 emerging as a 2 | Chemcomm.,