Rhodium-Catalyzed Asymmetric Hydrogenation of Olefins with PhthalaPhos, a New Class of Chiral Supramolecular Ligands

Nature makes wide use of non-covalent interactions to build its complex supramolecular architectures and to achieve efficient and selective transformations. In recent years, supramolecular approaches to the development of new enantioselective catalysts have gained momentum [1]. Herein we report the design and synthesis of a novel class of chiral monodentate phosphite ligands, named PhthalaPhos [2], which contain a phthalic acid diamide moiety (Figure 1). Such phthalamide group displays both donor and acceptor hydrogen bonding properties that can give rise to supramolecular interactions both between the ligands and with the substrate. The modular nature of the PhthalaPhos ligands allows to tune their properties by simply varying structural elements such as the linker, the BINOL unit and the ancillary amide group (i.e. the amide not connected to the phosphite group), thus allowing a parallel-combinatorial ligand optimization. Figure 1 The catalytic properties of the PhthalaPhos library (19 representatives) were tested in the rhodium-catalyzed enantioselective hydrogenation of dehydro aminoesters and N-acyl enamides. Excellent results in terms of catalytic activity and stereocontrol were obtained with both benchmark substrates and ‘challenging’, industrially relevant olefins (Figure 1). Spectroscopic and computational studies, together with control experiments, suggest that the role of the phthalamide group consists in binding and orientating (by hydrogen bonding) the substrate during the catalytic cycle of the hydrogenation process [2b].