Isotope effects and the mechanism of epoxidation of cyclohexenone with tert-butyl hydroperoxide
Isotope effects and the mechanism of epoxidation of cyclohexenone with tert-butyl hydroperoxide
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DOI：
10.1021/jo070777b
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发表时间：
2007-08-03
影响因子：
3.6
通讯作者：
Singleton, Daniel A.
中科院分区：
文献类型：
--
作者：
Christian, Chad F.;Takeya, Tetsuya;Singleton, Daniel A.
采用实验动力学同位素效应(Kies)和理论计算相结合的方法，研究了DBU催化2-环己烯-1-酮与叔丁基过氧化氢的环氧化反应机理。在环己酮的C-3(β)位观察到大的C-12/C-13(k(12C)/k(13C))同位素效应，约为1.032，而在C-2(α)位观察到小得多的C-12/C-13同位素效应，约为1.010。定性地，这些结果表明烯酮的亲核加成是速率限制步骤。理论计算支持这一解释。加成步骤的过渡结构导致预测的同位素效应与实验值接近，而闭环步骤的预测同位素效应与实验值不一致。计算正确地支持限速加成步骤，但表明加成步骤和环闭合步骤的势垒在能量上大致相似。这些环氧化反应的立体化学被预测为受初始轴向加成的偏好所支配，并讨论了这种偏好在实验非对映选择性观测中的作用。
The mechanism of the epoxidation of 2-cyclohexen-1-one with tert- butyl hydroperoxide mediated by DBU was studied by a combination of experimental kinetic isotope effects ( KIEs) and theoretical calculations. A large C-12/C-13 (k(12C)/k(13C)) isotope effect of approximate to 1.032 was observed at the C-3 (beta) position of cyclohexenone, while a much smaller C-12/C-13 isotope effect of 1.010 was observed at the C-2 (alpha) position. Qualitatively, these results are indicative of nucleophilic addition to the enone being the rate-limiting step. Theoretical calculations support this interpretation. Transition structures for the addition step lead to predicted isotope effects that approximate the experimental values, while the predicted isotope effects for the ring-closure step are not consistent with the experimental values. The calculations correctly favor a rate-limiting addition step but suggest that the barriers for the addition and ring-closure steps are crudely similar in energy. The stereochemistry of these epoxidations is predicted to be governed by a preference for an initial axial addition, and the role of this preference in experimental diastereoselectivity observations is discussed.