Bench-Stable Rh/Chiraphos Catalyzed Asymmetric Hydrogenation Reaction of Citral and Its Mechanistic Studies

Abstract

Although the Rh/chiraphos-catalyzed asymmetric hydrogenation of citral is a main industrial route to produce important chiral fragrance monomer l-menthol, this process still suffers from facile deactivation, strong substrate configuration dependence, and sub-optimal enantioselectivity, which mainly attributes to the poor understanding of its mechanism. In this work, we report the synthesis of an air-stable rhodium catalyst, [Rh(chiraphos)2]Cl, which enables over 10 recycling cycles in the asymmetric hydrogenation of citral without significant loss of activity or enantioselectivity (total turnover numbers, TONs, up to 10,000), demonstrating markedly improved stability and practical applicability. Combining experimental investigations with density functional theory (DFT) calculations, we systematically elucidate the mechanism of this asymmetric hydrogenation. The results show that the enantioselectivity and stereodependence are determined by the precise recognition of the citral head groups (CHO vs H) by the chiral cavity of the catalyst. Additionally, the chemoselectivity arises from the differences in deformation energies between the rhodium catalyst and citral caused by steric hindrance while maintaining maximum orbital overlap during the double-bond addition step. These findings offer a practical reference for the rational design of highly efficient and stereoconvergent catalytic systems for citral hydrogenation.