Development of Rigid Tricyclic Ligands and their Application to Asymmetric Catalysis

设计和开发过渡金属催化反应的手性配体是最具挑战性的课题。作为新单齿手性膦研究的一部分，我们成功地开发了一类新的手性配体，p -氮源二氨基膦氧化物，并将其应用于pd催化的四碳不对称结构。以天冬氨酸酸酐为原料，通过相应的二苯胺、三胺和相应的三氨基膦制备了对氮源二氨基膦氧化物。用x射线晶体结构分析明确了氧化二氨基膦的绝对结构。有了光学纯的p -氮源二氨基膦氧化物，我们试图将该分子用作手性磷配体，期望通过从二氨基膦氧化物(V)到二氨基羟基膦（III）的互变异构生成。催化对映选择性合成季碳中心是有机合成中一项具有挑战性的任务。我们首先研究了肉桂乙酸酯与2-氧环己烷羧酸乙酯的不对称烯丙基取代。在N， o -二（三甲基硅基）乙酰胺（BSA）和Zn(OAc)_2存在下，以（烯丙基pdcl）_2和二氨基膦氧化物为原料，反应顺利进行，产物的ee和定量收率达到92%。牛血清白蛋白是五价磷化合物向三价磷配体互变异构的优秀诱导剂。对配体结构优化的进一步研究正在进行中。

Design and development of chiral ligands for the transition-metal catalyzed reactions are most facinating and challenging task. As part of our research on development of new monodentate chiral phosphines, we succeeded in development of a new class of chiral ligands, P-chirogenic diaminophosphine oxides, and their application to Pd-catalyzed asymmetric construction of quarternary carbons.The P-chirogenic diaminophosphine oxides were prepared from aspartic acid anhydride via the corresponding dianilide, the triamine, and the corresponding triaminophosphine. The absolute structure of the diaminophosphine oxide was unequivocally determined by X-ray crystal structure analysis.With an optically pure P-chirogenic diaminophosphine oxide in hand, we attempted to use this molecule as a chiral phosphorus ligand, which expected to generate by tautomerization from the diaminophosphine oxide (V) to the diaminohydroxyphosphine (III). Catalytic enantioselective synthesis of a quaternary carbon center is a challenging task in organic synthesis. We first examined asymmetric allylie substitution of cinnamyl acetate with ethyl 2-oxo cyclohexane carboxylate. With the use of (allylPdCl)_2 and the diaminophosphine oxide, the reaction smoothly proceeded in the presence of N,O-bis(trimethylsilyl)acetamide (BSA) and Zn(OAc)_2 to afford the product in 92% ee and quantitative yield. BSA was found to be excellent inducer of tautomerism from the pentavalent phosphorus compound to the trivalent phosphorus ligand.Further investigation on optimization of ligand structure are in progress.