Since Akiyama and Terada independently reported the introduction of chiral phosphoric acids (CPAs) as effective catalysts for Mannich-type reactions in 2004, the field of CPA catalysis has grown immensely. Terada reported in 2008 the first example of the activation of aldehydes by a CPA. Based on density functional theory (DFT) calculations, Terada proposed a dual activation mode for this enantioselective aza–ene-type reaction between an aldehyde and an enecarbamate. In this model, hydrogen bonds between the catalyst’s hydroxyl group and the carbonyl oxygen and the catalyst’s P═O and the formyl proton were observed; the nucleophile then attacks without coordination to the catalyst. This reaction model provided the mechanistic basis for understanding Terada’s reaction and many other asymmetric transformations. In the present study, DFT calculations are reported that identify a lower-energy mechanism for this landmark reaction. In this new model, hydrogen bonds between the catalyst’s hydroxyl group and the aldehyde oxygen and the catalyst’s P═O and the NH group of the enecarbamate are seen. The new model rationalizes the stereoselective outcome of Terada’s reaction and offers insight into why a more sterically demanding catalyst gives lower levels of enantioselectivity.

中文翻译：

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手性磷酸催化：重新审视 Terada 模型

自从 Akiyama 和 Terada 于 2004 年独立报道引入手性磷酸 (CPA) 作为曼尼希型反应的有效催化剂以来，CPA 催化领域得到了极大的发展。Terada 在 2008 年报道了第一个通过 CPA 活化醛的例子。基于密度泛函理论 (DFT) 计算，Terada 为醛和烯氨基甲酸酯之间的这种对映选择性氮杂-烯型反应提出了双重激活模式。在该模型中，观察到催化剂的羟基与羰基氧和催化剂的 P=O 和甲酰基质子之间的氢键；然后亲核试剂在不与催化剂协调的情况下进行攻击。该反应模型为理解 Terada 的反应和许多其他不对称转化提供了机理基础。在目前的研究中，据报道，DFT 计算确定了这一具有里程碑意义的反应的低能量机制。在这个新模型中，可以看到催化剂的羟基和醛氧以及催化剂的 P=O 和烯氨基甲酸酯的 NH 基团之间的氢键。新模型使 Terada 反应的立体选择性结果合理化，并深入了解了为什么空间要求更高的催化剂会产生较低水平的对映选择性。