Development and Application of New Chiral Ligand Systems Effective for Catalytic Asymmetric Carbon-Carbon Bond Formation

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New chiral P,N type ligands were designed and prepared starting from L-valinol and (R)-binaphthol for catalytic asymmetric conjugate addition of dialkylzinc to enones. By condensation of a chiral component, (S)-1-(diphenylphosphino)-3-methyl-2-butanamine, with pyridine-2-carboxylic acids and pyridine-2-carboxaldehydes, new amide-type and imine-type P,N ligands bearing pyridyl groups were obtained. For evaluation of the ligands, asymmetric conjugate addition of diethylzinc to 2-cyclohexen-1-one was carried out using copper triflate (1 mol%) as the catalyst. The pyridylmethylene derivatives (imine-type ligands) were found to be very efficient ligands having high enantioselectivity up to 95% ee, though the amide-type ligands showed lower enantioselectivity (below 66% ee). On the other hand, the enantioselectivity of the conjugate addition to an acyclic enone, chalcone, was lower and only a moderate selectivity (up to 71% ee) was obtained even by using the imine-type ligands. The enantioselectivity of the amide-type ligand was improved by alkylation of the NH group, and the smallest N-Me derivative showed the highest selectiveity (81% ee (cyclohexenone), 75% ee (chalcone)). Several N-sulfonyl derivatives of the chiral component were prepared and the selectivity of an N-(1R)-10-camphorsulfonyl derivative (73% ee) was better than that of the others in the reaction of 2-cyclohexen-1-one. An axially chiral 1,1'-binaphthyl ligand bearing both 2-tosylamino and 2'-diphenylphosphino groups was synthesized through a new convenient route using (R)-2-cyano-2'-phosphinyl-1,1'-binaphthyl as a synthetic intermediate. The new ligand was found to be highly efficient in the copper-catalyzed conjugate addition of diethylzinc to benzylideneacetones, showing high selectivity of 84-99% ee.