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

新型手性杂化配体的开发及其在催化不对称合成中的应用

基本信息

批准号：
11672111
负责人：
MORIMOTO Toshiaki
金额：
$ 2.18万
依托单位：
University of Shizuoka
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

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.

以α-氨基酸还原得到的β-氨基醇为原料，合成了β-二苯基膦基烷基胺，并以较高的总收率，一步合成了膦脒型、膦亚胺型（P，N-杂合配体）和双（酰胺膦）型（P，P-对称配体）等新型手性配体.在BSA和AcOLi存在下，脒类配体VA_2和N-亚苄基上带有给电子基团（p-Me_2N-）的亚胺类配体都是钯催化的无环烯丙基酯1，3-二苯基-2-丙烯酯与丙二酸二甲酯的不对称烯丙基烷基化反应的有效配体（>90% ee）。亚胺类配体对位引入给电子基团后，对映选择性和催化活性都有显著提高。在烯丙基烷基化反应中，用烯酮甲硅烷基缩醛代替相应的单酯碳负离子作为亲核试剂，也得到了高的对映选择性，单酯碳负离子比丙二酸碳负离子更硬，效率更低。另一方面，发现带有邻苯二甲酰基间隔基的双（酰胺-膦）型配体对于Pd催化的环烯丙基酯2-环己烯基酯的烯丙基烷基化是高度对映选择性的配体（> 99%ee）。在1，3-二苯基-2-丙烯酯的烯丙基烷基化反应中，发现了带有不同链烷烃间隔基的双（酰胺-膦）型配体的不寻常的手性反转。研究了铑催化的酮的不对称硅氢化反应。提出了Pr/Mr手性的概念，并将其用于手性双齿配体的分类，发现配体的Pr/Mr手性与烯丙基化产物的绝对构型有很好的相关性.