Phosphoric Acid Catalyzed Enantioselective Transfer Hydrogenation of Imines: A Density Functional Theory Study of Reaction Mechanism and the Origins of Enantioselectivity
Phosphoric Acid Catalyzed Enantioselective Transfer Hydrogenation of Imines: A Density Functional Theory Study of Reaction Mechanism and the Origins of Enantioselectivity
复制标题
DOI：
10.1002/chem.200800890
复制
发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Himo, Fahmi
中科院分区：
文献类型：
--
作者：
Marcelli, Tommaso;Hammar, Peter;Himo, Fahmi
采用密度泛函理论研究了磷酸催化的1,4-二氢吡啶与N-芳基亚胺的反应。我们首先考虑了苯乙酮PMP-亚胺（PMP=对甲氧基苯基）与磷酸二苯酯催化的二甲基Hantzsch酯的反应。我们的研究表明，与之前对其他反应的假设一致，磷酸二苯酯在此转化中充当路易斯碱/布朗斯台德酸双功能催化剂，同时激活两个反应伙伴。计算还表明，亚胺离子的 E 和 Z 异构体的氢化物转移过渡态具有相当的能量。这一观察结果对于理解该过程的对映选择性至关重要。我们的结果表明，当使用手性 3,3'-二取代联芳基磷酸时，氢化物转移到 (Z)-亚胺鎓 Re 面在能量上更有利，并负责对映选择性，而 (E)-亚胺鎓两个面上亲核攻击的相应过渡态实际上是简并的。此外，模型计算预测了在 2-芳基喹啉氢化中观察到的对映选择性的逆转，2-芳基喹啉在催化循环过程中转化为 (E)-亚胺离子，该离子缺乏源自无环 N-芳基亚胺的灵活性。在这方面，二氢喹啉鎓阳离子的构象刚性对Re面上氢化物转移的过渡态施加了不利的结合几何形状，因此导致了高对映选择性。
The phosphoric acid catalyzed reaction of 1,4-dihydropyridines with N-arylimines has been investigated by using density functional theory. We first considered the reaction of acetophenone PMP-imine (PMP=p-methoxyphenyl) with the dimethyl Hantzsch ester catalyzed by diphenyl phosphate. Our study showed that, in agreement with what has previously been postulated for other reactions, diphenyl phosphate acts as a Lewis base/ Bronsted acid bifunctional catalyst in this transformation, simultaneously activating both reaction partners. The calculations also showed that the hydride transfer transition states for the E and Z isomers of the iminium ion have comparable energies. This observation turned out to be crucial to the understanding of the enantioselectivity of the process. Our results indicate that when using a chiral 3,3'-disubstituted biaryl phosphoric acid, hydride transfer to the Re face of the (Z)-iminium is energetically more favorable and is responsible for the enantioselectivity, whereas the corresponding transition states for nucleophilic attack on the two faces of the (E)-iminium are virtually degenerate. Moreover, model calculations predict the reversal in enantioselectivity observed in the hydrogenation of 2-arylquinolines, which during the catalytic cycle are converted into (E)-iminium ions that lack the flexibility of those derived from acyclic N-arylimines. In this respect, the conformational rigidity of the dihydroquinolinium cation imposes an unfavorable binding geometry on the transition state for hydride transfer on the Re face and is therefore responsible for the high enantioselectivity.