Asymmetric Hydrogenations : Syntheses of Ligands and Expansion of Substrate Scope

Abstract: Asymmetric hydrogenation has emerged as a versatile methodology to obtain a wide range of chiral precursors. This thesis focused on the synthesis of new chiral ligands and the expansion of the substrate scope of asymmetric hydrogenations. Paper I described the synthesis and evaluation of N,P-ligands for the Ir-catalyzed hydrogenations of unfunctionalized olefins. The substrate scope of Ir-catalyzed asymmetric hydrogenations is limited to a narrow range of “test” olefins. The foremost focus of this thesis was to expand the substrate scope of Ir-catalyzed asymmetric hydrogenations. Papers II and III disclosed the potential of the N,P-ligated Ir complexes in hydrogenation of the enol phosphinates. This substrate class is attractive because the hydrogenated products are chiral alkylphosphinates that can be transformed into chiral alcohols and chiral phosphines without sacrificing enantiopurity. A wide range of enol phosphinates were hydrogenated to excellent conversions and enatioselectivities. The hydrogenation of purely alkyl-substituted enol phosphinates in very high conversions and ee values was emphasized in these studies. Paper IV described the investigation of unfunctionalized enamines as substrates in Ir-catalyzed hydrogenation studies. The hydrogenation results and structural limitations of the substrates are presented. Paper V described the asymmetric hydrogenation of diphenylvinylphosphine oxides, di- and trisubstituted vinyl phosphonates. The hydrogenation of diphenylvinylphosphine oxides gives direct access to protected chiral phosphines. The hydrogenated products of vinylphosphonates are highly synthetically useful in pharmaceutical and material chemistry. Hydrogenation of E/Z mixtures of carboxyethyl vinylphosphonates with perfect enantioselectivities was striking in these studies. In paper VI, we have reported the development of a new, highly enantioselective synthetic route to building blocks with CF3 at the chiral center. Several functionalized and unfunctionalized CF3-substituted olefins were hydrogenated with varied degree of success. This methedilogy is useful in the formation of chiral fluorine-containing molecules for a wide range of applications. Paper VII described the hydrogenation of imines using the phosphine-free Cp'Ru/diamine complexes. Chiral version of this reaction was also examined. Despite the modest results, this is the first study to use phosphine-free Cp'Ru/diamine complexes as catalysts for the reduction of C=N double bonds.