Development of a heterogeneous P–N–N tridentate ligand for iridium-catalyzed asymmetric hydrogenation of ketones in batch and flow

Abstract

Immobilization of chiral catalysts, which are composed of precious metals and costly ligands, offers an economical and environmentally-friendly strategy. However, several challenges remain, including inferior activity and selectivity compared to homogeneous counterparts, complex synthetic procedures and most notably, the low stability of catalytically active sites. For asymmetric hydrogenation, supported monodentate and bidentate ligands have been extensively developed, whereas the immobilization of multidentate ligands remains largely unexplored. These ligands are characterized by a stable tridentate-chelating mode and a deeper chiral pocket. In this study, we present the successful development of polymer-supported tridentate ligands designed for iridium catalyzed asymmetric hydrogenation. These robust catalysts not only have a simple preparation process but also exhibit excellent activity and selectivity towards a wide variety of ketones (up to 99% yield, >99% ee and 99 : 1 dr), which was comparable to that of their homogeneous counterparts. Furthermore, their stability and industrial potential were demonstrated through successful applications in both batch recycling and continuous flow processes, especially in continuous hydrogenation, where they facilitated the synthesis of a key intermediate of bepotastine besilate with a higher TON of 30 290, even under lower pressure in comparison with the homogeneous system.