一类基于桥链手性传递构建双膦配体的设计合成及其不对称催化反应研究

The design and development of new chiral ligands for efficient chirality transfer has a pivotal role in transition metal catalyzed asymmetric reactions. In this regard, chelating diphosphine ligands with an atropisomeric biaryl scaffold proved to be highly efficient chiral inducers in many enantioselective transformations. Despite the extensive design of the atropisomeric diphosphines, the existing atropisomeric biaryl diphosphine ligands possess at least one ortho substituent at the biaryl skeleton. Several studies revealed the influence of the bite angles in the chiral diphosphines on the reactivity and selectivity of some catalytic reactions, and optimal dihedral angles are essential for attaining high enantioselectivities in asymmetric catalysis. Meanwhile, the tedious resolution procedures for acquiring enantiomerically pure diphosphine ligands also hindered the research.. In this project, a series of chiral ligands would be prepared by atropdiastereo-selective ring-closure reactions. The substrate-directed.diastereomeric ring-closure reaction is unprecedented for the preparation of chiral biaryl backbone, and our method precludes the tedious resolution procedures usually required for preparing enantiomerically pure ligands. The effect of chiral recognition would also be revealed in a relevant asymmetric ring-closure reaction. The chiral tether bridging the two aryl units creates a conformationally rigid scaffold essential for enantiofacial differentiation; fine-tuning of the ligand scaffold (e.g., dihedral angles) can be achieved by varying the chain length of.the chiral tether and this property would be the key to success in the development of highly regiodiastereo- and enantioselective reactions. The new ligands would be a class of versatile ligands for desymmetrization of mesoconfigurated and prochiral substrates.

以BINAP为代表的轴手性双膦配体在不对称催化中的成功应用，激发了大量具有联苯骨架轴手性配体的设计与研究。但传统的6,6’位联苯轴手性配体普遍受到阻转基团对其二面角范围的局限，同时双膦配体合成中也存在手性分离困难等问题，这些都严重制约着该类配体的开发与应用。. 本项目拟设计合成一类具有手性桥链的5,5'位联苯双膦配体，并将其应用到多种不对称催化反应中。项目利用廉价易得的手性化合物为桥链，通过桥链手性模板的传递效应，高非对映体选择性地得到所期望构型的配体。目标配体不仅具有5,5'位联苯配体固有的大范围可调二面角优势，同时还能够通过普通硅胶柱进行分离纯化，不需要手性拆分，可以简单廉价地大规模合成。大范围的二面角同桥链引入的手性因素相结合，可以为不对称催化配体库筛选提供更多实用、新型、高效的催化剂和催化体系，并为联苯双膦配体的工业应用这一富有挑战性的课题提供一条可行途径。

以BINAP为代表的轴手性双膦配体在不对称催化中的成功应用，激发了大量具有联苯骨架轴手性配体的设计与研究。但传统的6,6’位联苯轴手性配体普遍受到阻转基团对其二面角范围的局限，同时双膦配体合成中也存在手性分离困难等问题，这些都严重制约着该类配体的开发与应用。.本项目设计合成了一类具有手性桥链的5,5'位联苯双膦配体，利用廉价易得的手性化合物为桥链，通过桥链手性模板的传递效应，高非对映体选择性地得到了所期望构型的配体，目标配体能够通过普通硅胶柱进行分离纯化，不需要手性拆分。我们还将手性膦配体化合物分别与不同金属生成了系列手性金属络合物，并将上述手性金属络合物应用于钯催化分子内α-羰基酰苯胺芳基化，铱催化喹啉不对称氢化反应研究，钌金属络合物催化α-羰基酸乙酯的氢化反应，汞及金络合物催化重氮化合物对苯乙烯环丙烷化反应等等不对称催化反应研究，对新配体的各种适用反应条件进行了考察。新配体易于合成，兼具有大范围可调二面角的特点，为不对称催化配体库筛选提供更多实用、新型、高效的催化剂和催化体系，并为联苯双膦配体的工业应用这一富有挑战性的课题提供一条可行途径。