Development of new chiral hetero-hybrid ligands and their use in catalytic asymmetric synthesis

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Several new types of chiral ligands such as phosphine-amidine-type and phosphine-imine-type ligands (P,N-hetero-hybrid ligands) and bis (amide-phosphine)-type ligands (P,P-symmetric ligands) were prepared in one step from versatile chiral components, β-(diphenylphosphino) alkylamines, which were synthesized in good overall yields from β-aminoalcohols obtained by reduction of α-amino acids. Both an amidine-type ligand VALAP and an imine-type ligand bearing an electron-donating group (p-Me_2N-) at the N-benzylidene group were found to be efficient ligands (>90% ee) in palladium-catalyzed asymmetric allylic alkylation of an acyclic allyl ester, 1,3-diphenyl-2-propenyl ester, with dimethyl malonate in the presence of BSA and AcOLi. Electron-donating groups at the p-position of the imine-type ligands were revealed to bring considerarble improvements of the enantioselectivity and the catalytic activity. High enantioselectivity was also obtained in the allylic alkylation by using ketene silyl acetals as nucleophiles in place of the corresponding monoester carbanions which are harder and less efficient nucleophiles than the malonate carbanion. On the other hand, a bis (amide-phosphine)-type ligand bearing a phthaloyl spacer was found to be a highly enantioselective ligand (>99% ee) for Pd-catalyzed allylic alkylation of a cyclic allyl ester, 2-cyclohexenyl ester. With analogous bis (amide-phosphine)-type ligands bearing different alkane spacers, an unusual reversal of chirality was observed in the allylic alkylation of 1,3-diphenyl-2-propenyl ester. Asymmetric rhodium-catalyzed hydrosilylation of ketones was also examined with the P,P-ligands. A useful concept of Pr/Mr-chirality was proposed for classification of all chiral bidentate ligands and a good correlation was observed between the Pr/Mr-chirality of the ligands and the absolute configuration of the allylation products.