Scope and mechanism of asymmetric C(sp3)-H/C(Ar)-X coupling reactions: computational and experimental study
Scope and mechanism of asymmetric C(sp3)-H/C(Ar)-X coupling reactions: computational and experimental study
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DOI：
10.1039/c3sc00098b
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发表时间：
2013-01-01
期刊：
影响因子：
8.4
通讯作者：
Kuendig, E. Peter
中科院分区：
文献类型：
--
作者：
Larionov, Evgeny;Nakanishi, Masafumi;Kuendig, E. Peter
报道了通过未活化的亚甲基/甲基的不对称 C(sp(3))-H 活化，在钯-NHC 催化下有效合成高度对映体富集的 2,3-反式融合和 2-烷基二氢吲哚方面取得了进展。在 120 至 160 摄氏度的反应温度下实现了非常高的不对称诱导（高达 99% ee）。研究了影响反应效率的因素（卤化物、拟卤化物、N-保护基团）。通过详细的密度泛函理论 (DFT) 计算（M06-L 泛函）探讨了反应途径和对映体选择。理论和实验相结合的研究表明，Pd-NHC 催化的 C(sp(3))-H 芳基化是通过协同金属化-去质子化 (CMD) 机制进行的。 DFT 计算和动力学同位素效应测量表明 CMD 步骤是选择性决定的。观察到实验对映选择性与非对映异构体活化屏障之间的计算差异之间具有良好的一致性。
Advances in the efficient palladium-NHC catalysed synthesis of highly enantioenriched 2,3-trans-fused and 2-alkyl indolines via asymmetric C(sp(3))-H activation of an unactivated methylene/methyl group are reported. Very high asymmetric inductions (up to 99% ee) were achieved at reaction temperatures ranging from 120 to 160 degrees C. Factors influencing the efficiency of the reaction (halide, pseudohalide, N-protecting group) were investigated. The reaction pathway and enantioselection were probed by detailed density functional theory (DFT) calculations (M06-L functional). The combined theoretical and experimental study shows that the Pd-NHC catalysed C(sp(3))-H arylation proceeds via a concerted metalation-deprotonation (CMD) mechanism. The CMD step is shown by DFT calculations and kinetic isotope effect measurements to be selectivity-determining. A good agreement between experimental enantioselectivities and calculated differences amongst diastereomeric activation barriers is observed.