Mechanism and Selectivity of N-Triflylphosphoramide Catalyzed (3++2) Cycloaddition between Hydrazones and Alkenes
Mechanism and Selectivity of N-Triflylphosphoramide Catalyzed (3++2) Cycloaddition between Hydrazones and Alkenes
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DOI：
10.1021/ja506660c
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发表时间：
2014-10-01
影响因子：
15
通讯作者：
Houk, K. N.
中科院分区：
文献类型：
--
作者：
Hong, Xin;Kucuk, Hatice Baspinar;Houk, K. N.
Bronsted酸在腙和烯烃之间催化（3(+)+ 2）环加成提供了一种合成吡唑烷的一般方法。Bronsted酸的酸度对催化效率至关重要，酸性较弱的磷酸是无效的，而高酸性的n -三氟基手性磷酰胺是非常有效的，可以促进高对端选择性的环加成。用密度泛函理论（M06-2X）计算探讨了这些反应的催化效率和选择性的机理和来源。n -三氟酰磷酰胺使腙发生质子化反应，产生腙-磷酰胺阴离子配合物。这些离子对配合物与烯烃进行（3(+)+ 2）环加成反应，生成吡唑烷产物。替代的1,3-偶极（3 + 2）环加成与类似的亚甲亚胺是不太有利的，因为腙的内生异构化到亚甲亚胺。在n-三氟酰磷酰胺催化剂中，离子对配合物只需要很小的畸变就能达到（3(+)+ 2）环加成过渡态的几何形状。相反，弱磷酸不使腙质子化，只形成一个氢键配合物。在环加成过渡态，氢键配合物需要较大的畸变能才能达到“离子对”的几何形状，并且存在明显的势垒。在此机制的基础上，我们解释了当使用手性n -三氟基磷酰胺催化剂时对映选择性的起源。我们还报道了将烯烃的底物范围扩展到乙基乙烯醚和硫醚的实验研究。
Bronsted acid catalyzed (3(+) + 2) cycloadditions between hydrazones and alkenes provide a general approach to pyrazolidines. The acidity of the Bronsted acid is crucial for the catalytic efficiency the less acidic phosphoric acids are ineffective, while highly acidic chiral N-triflylphosphoramides are very efficient and can promote highly enantioselective cycloadditions. The mechanism and origins of catalytic efficiencies and selectivities of these reactions have been explored with density functional theory (M06-2X) calculations. Protonation of hydrazones by N-triflylphosphoramide produces hydrazonium-phosphoramide anion complexes. These ion-pair complexes are very reactive in (3(+) + 2) cycloadditions with alkenes, producing pyrazolidine products. Alternative 1,3-dipolar (3 + 2) cycloadditions with the analogous azomethine imines are much less favorable due to the endergonic isomerization of hydrazone to azomethine imine. With N-triflylphosphoramide catalyst, only a small distortion of the ion-pair complex is required to achieve its geometry in the (3(+) + 2) cycloaddition transition state. In contrast, the weak phosphoric acid does not protonate the hydrazone, and only a hydrogen-bonded complex is formed. Larger distortion energy is required for the hydrogen-bonded complex to achieve the "ion-pair" geometry in the cycloaddition transition state, and a significant barrier is found. On the basis of this mechanism, we have explained the origins of enantioselectivities when a chiral N-triflylphosphoramide catalyst is employed. We also report the experimental studies that extend the substrate scope of alkenes to ethyl vinyl ethers and thioethers.