手性磷酰胺类化合物不对称催化合成α-芳基丙醇类化合物

Asymmetric Synthesis of α-Arylpropanol Compounds by Chiral Phosphoramide Compounds Catalysts

对一系列磷酰胺类化合物进行了考察,发现以芳香醛类化合物与二乙基锌作为底物,手性磷酰胺类化合物4a(N-((1R,2R)-2-(异丙基氨基)-1,2-二苯基乙基)-P,P-二苯基次膦酰胺)作为催化剂,通过发生不对称还原反应合成具有生理活性的α-芳基丙醇类化合物.手性磷酰胺类化合物合成所使用的起始物料不仅廉价易得,而且催化效率也比较高.在优化出的最优反应条件下,4a的使用量为10%(摩尔分数),可以高选择性、高产率地催化合成手性α-芳基丙醇类化合物,且手性磷酰胺类化合物可以回收利用.通过反应机理研究,提出催化反应过程中形成的含有四元、六元过渡态以及空间位阻作用的中间态是导致所得α-芳基丙醇类化合物有较高的ee值的决定步骤.

Chiral α-arylpropanol compounds with important biological activity were synthesized with high yield and catalytic efficiency from thiophosphoramide 4 a(N-((1 R,2 R)-2-(isopropylamino)-1,2-diphenylethyl)-P,Pdiphenylphosphinicamide)as catalyst,aromatic aldehydes and diethylzinc as reactants by catalytic asymmetric reduction reaction.The raw materials for 4 a are cheap and easy to obtain.Under the optimal conditions(the usage amount of 4 a is 10%(Mole fraction)),chiral α-arylpropanol compounds can be synthesized with high yield and e.e.value.4 a was very convenient to recycle and reuse in this system.It is proposed that the intermediate states containing quaternary and six-member transition states and steric hindrance formed during the catalytic reactionare beneficial to improve the enantioselectivity of the reaction.