Comprehensive mechanistic studies on the enantioselective aldol reaction between isatin (1 a) and acetone, catalyzed by L‐leucinol (3 a), unraveled that isatin, apart from being a substrate, also plays an active catalytic role. Conversion of the intermediate oxazolidine 4 into the reactive syn‐enamine 6, catalyzed by isatin, was identified as the rate‐determining step by both the calculations (ΔG^≠=26.1 kcal mol⁻¹ for the analogous L‐alaninol, 3 b) and the kinetic isotope effect (k_H/k_D=2.7 observed for the reaction using [D₆]acetone). The subsequent reaction of the syn‐enamine 6 with isatin produces (S)‐2 a (calculated ΔG^≠=11.6 kcal mol⁻¹). The calculations suggest that the overall stereochemistry is controlled by two key events: 1) the isatin‐catalyzed formation of the syn‐enamine 6, which is thermodynamically favored over its anti‐rotamer 7 by 2.3 kcal mol⁻¹; and 2) the high preference of the syn‐enamine 6 to produce (S)‐2 a on reaction with isatin (1 a) rather than its enantiomer (ΔΔG^≠=2.6 kcal mol⁻¹).

中文翻译：

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芥子醇催化的Isatin与丙酮的交叉Aldol反应：机理研究

上靛红（之间的对映选择性醛醇缩合反应的综合机理研究1）和丙酮，用催化的大号-leucinol（3），该拆散靛红，除了是一基板，也起着积极的促进作用。中间恶唑烷的转化4到反应性顺式-烯胺6，由靛红催化，被确定为所述速率确定步骤通过两者的计算（Δ ģ ^≠ = 26.1千卡摩尔^-1的类似大号-alaninol，图3b）以及动力学同位素效应（k _H / k _D使用[D ₆ ]丙酮观察到＝ 2.7的反应。合成烯胺6与靛红的后续反应产生（S）-2 a（计算得出的ΔG ^≠ = 11.6 kcal mol ^-1）。计算表明，整体立体化学受两个关键事件控制：1）合成酶催化的合成烯胺6的形成，在热力学上胜过其抗旋转异构体7的量为2.3 kcal mol ^-1；和2）合成烯胺6对生产（S） - 2上反应与靛红（1），而不是它的对映体（ΔΔ ģ ^≠ = 2.6千卡摩尔^-1）。