Development of Rigid Tricyclic Ligands and their Application to Asymmetric Catalysis

过渡金属催化反应中手性配体的设计与开发是一个极具挑战性的课题。作为新型单齿手性膦配体开发研究的一部分，我们成功地开发了一类新型手性配体--P-手性二氨基氧化膦，并将其应用于钯催化的不对称季碳构筑反应中，以天冬氨酸酐为原料，通过相应的二酰苯胺、三胺和三氨基膦合成了P-手性二氨基氧化膦。通过X-射线晶体结构分析确定了二氨基氧化膦的绝对结构，利用光学纯的手性二氨基氧化膦，我们尝试将其作为手性磷配体，通过互变异构反应从二氨基氧化膦（V）生成二氨基羟基膦（III）。季碳中心的催化不对称合成是有机合成中一个具有挑战性的课题。我们首先研究了乙酸肉桂酯与2-氧代环己烷羧酸乙酯的不对称烯丙基取代反应。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和二氨基氧化膦为催化剂，反应顺利进行，产物的ee值和定量产率为92%。BSA是五价磷化合物与三价磷配体互变异构的良好诱导剂，配体结构的优化正在进行中。

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.