Synthesis of triphosphorous bidentate phosphine-phosphoramidite ligands: application in the highly enantioselective hydrogenation of ortho-substituted aryl enamides.

The development of new effective chiral ligands is fundamental to asymmetric hydrogenation. Over recent decades, many excellent bisphosphine ligands have been reported for highly enantioselective hydrogenation reactions. However, the modification of a desired structural motif of most bidentate ligands is impeded by multistep synthesis. Recently, this situation has been partially remedied by the emerging monodentate ligands, including phosphoramidites, phosphonites, and phosphites, which have modular structures and can be prepared in one step from chiral binaphthol (BINOL) or its analogues. As part of our continuous interest in exploring new ligands for hydrogenation, we wonder whether the design of new bidentate ligands can benefit from the advantages of modular monodentate ligands for further structural optimization. From a practical viewpoint, ligands should be prepared in a few steps from readily available starting materials. Although various modified BINOL ligands have been utilized for asymmetric catalysis, few efforts have been made to attach the phosphorous group directly at the 3,3’-positions. Inspired by the success of many hybrid C1symmetric chelating ligands, we herein report the synthesis and application of a new phosphine–phosphoramidite ligand 1. To our knowledge, this pseudo-C2-symmetric triphosphorous bidentate ligand is the first of its class and represents a conceptually new approach to ligand design. Importantly, unprecedented enantioselectivities have been achieved with this new ligand for the hydrogenation of ortho-substituted aryl enamides and a 1-naphthylenamide, thereby solving a long-standing problem in the hydrogenation of enamides. Ligand 1 was synthesized in four steps from (R)-BINOL (Scheme 1). Protection of the hydroxy groups of BINOL was