Department of Chemistry, Dr. Harisingh Gour Central University , Sagar 470003, India.
Department of Material Chemistry, Graduate School of Engineering, Kyoto University , Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
J Org Chem. 2017 Jan 6;82(1):289-301. doi: 10.1021/acs.joc.6b02394. Epub 2016 Dec 27.
Selective alkenylation of pyridine is challenging in synthetic organic chemistry due to the poor reactivity and regioselectivity of the aromatic ring. We theoretically investigated Ni-catalyzed selective alkenylation of pyridine with DFT. The first step is coordination of the pyridine-AlMe adduct with the active species Ni(NHC)(CH) 1 in an η-fashion to form an intermediate Int1. After the isomerization of Int1, the oxidative addition of the C-H bond of pyridine across the nickel-acetylene moiety occurs via a transition state TS2 to form a Ni(NHC) pyridyl vinyl intermediate Int3. This oxidative addition is rate-determining. The next step is C-C bond formation between pyridyl and vinyl groups leading to the formation of vinyl-pyridine (P1). One of the points at issue in this type of functionalization is how to control the regioselectivity. With the use of Ni(NHC)/AlMe catalyst, the C- and C-alkenylated products (ΔG° = 17.4 and 21.5 kcal mol, respectively) are formed preferably to the C one (ΔG° = 22.0 kcal mol). The higher selectivity of the C-alkenylation over the C and the C ones is attributed to the small steric repulsion between NHC and AlMe in the C-alkenylation. Interestingly, with Ni(P(i-Pr))/AlMe catalyst, the C-alkenylation occurs more easily than the C and C ones. This regioselectivity arises from the smaller steric repulsion induced by P(i-Pr) than by bulky NHC. It is notable that AlMe accelerates the alkenylation by inducing the strong CT from Ni to pyridine-AlMe. In the absence of AlMe, pyridine strongly coordinates with the Ni atom through the N atom, which increases Gibbs activation energy (ΔG° = ∼27 kcal mol) of the C-H bond activation. In other words, AlMe plays two important roles, acceleration of the reaction and enhancement of the regioselectivity for the C-alkenylation.
由于芳香环的反应性和区域选择性差，吡啶的选择性烯基化在合成有机化学中具有挑战性。我们使用 DFT 理论研究了 Ni 催化的吡啶的选择性烯基化。第一步是吡啶-AlMe 加合物与活性物种 Ni(NHC)(CH) 1 以 η 方式配位，形成中间体 Int1。Int1 异构化后，吡啶的 C-H 键通过过渡态 TS2 穿过镍-乙炔部分发生氧化加成，形成 Ni(NHC)吡啶乙烯基中间体 Int3。该氧化加成是速率决定步骤。下一步是吡啶和乙烯基之间的 C-C 键形成，导致乙烯基-吡啶 (P1) 的形成。这种官能化的一个争议点是如何控制区域选择性。使用 Ni(NHC)/AlMe 催化剂，优先形成 C-和 C-烯基化产物（ΔG°分别为 17.4 和 21.5 kcal mol），而不是 C-烯基化产物（ΔG°为 22.0 kcal mol）。C-烯基化比 C 和 C 烯基化具有更高的选择性归因于 C-烯基化中 NHC 和 AlMe 之间的小空间排斥。有趣的是，使用 Ni(P(i-Pr))/AlMe 催化剂，C-烯基化比 C 和 C 更容易发生。这种区域选择性源于 P(i-Pr) 引起的空间排斥比大体积的 NHC 小。值得注意的是，AlMe 通过诱导从 Ni 到吡啶-AlMe 的强 CT 加速烯基化。在没有 AlMe 的情况下，吡啶通过 N 原子与 Ni 原子强烈配位，这增加了 C-H 键活化的吉布斯活化能 (ΔG°约为 27 kcal mol)。换句话说，AlMe 发挥了两个重要作用，即加速反应和增强 C-烯基化的区域选择性。
