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

以β-氨基酸还原得到的β-氨基醇为原料，合成了多种手性组分α-(二苯基膦)烷基胺，一步合成了膦-胺型、膦-亚胺型(P，N-杂化配体)和双(酰胺-膦)型(P，P-对称配体)等新型手性配体。在钯催化的1，3-二苯基-2-丙烯酸二甲酯与丙二酸二甲酯的不对称烯丙基化反应中，酰胺型配体VALAP和亚胺型配体(p-Me_2N-)均被发现是催化钯催化丙二酸二甲酯不对称烯丙基化反应的有效配体。亚胺类配体的p位给电子基团能显著提高对映体的选择性和催化活性。在烯丙基烷基化反应中，用烯酮硅基缩醛代替相应的单酯碳负离子也获得了较高的对映体选择性，单酯碳负离子比丙二酸碳负离子更硬，效率更低。另一方面，一个带有邻苯二甲酰基间隔的双(酰胺-膦)型配体被发现是一种高对映选择性的配体(&gt；99%ee)，用于Pd催化的环烯丙基酯-2-环己烯酯的烯丙基烷基化反应。当类似的双(酰胺-膦)型配体具有不同的烷基间隔时，1，3-二苯基-2-丙烯基酯的烯丙基烷基化反应中观察到手性的反转。还考察了P，P-配体催化的酮的不对称硅氢化反应。提出了一个有用的Pr/MR手性概念用于所有手性双齿配体的分类，并观察到配体的Pr/MR手性与烯丙化产物的绝对构型之间有很好的相关性。

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.