title: Theoretical Study of Nickel-Catalyzed Selective Alkenylation of Pyridine: Reaction Mechanism and Crucial Roles of Lewis Acid and Ligands in Determining the Selectivity.
abstract: 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-AlMe3adduct with the active species Ni(0)(NHC)(C2H2) 1 in an η2-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(II)(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)/AlMe3catalyst, the C4- and C3-alkenylated products (ΔG°⧧= 17.4 and 21.5 kcal mol-1, respectively) are formed preferably to the C2one (ΔG°⧧= 22.0 kcal mol-1). The higher selectivity of the C4-alkenylation over the C3and the C2ones is attributed to the small steric repulsion between NHC and AlMe3in the C4-alkenylation. Interestingly, with Ni(P(i-Pr)3)/AlMe3catalyst, the C2-alkenylation occurs more easily than the C3and C4ones. This regioselectivity arises from the smaller steric repulsion induced by P(i-Pr)3than by bulky NHC. It is notable that AlMe3accelerates the alkenylation by inducing the strong CT from Ni to pyridine-AlMe3. In the absence of AlMe3, pyridine strongly coordinates with the Ni atom through the N atom, which increases Gibbs activation energy (ΔG°⧧= ∼27 kcal mol-1) of the C-H bond activation. In other words, AlMe3plays two important roles, acceleration of the reaction and enhancement of the regioselectivity for the C4-alkenylation.
authors.affiliation: Department of Chemistry, Dr. Harisingh Gour Central University , Sagar 470003, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Material Chemistry, Graduate School of Engineering, Kyoto University , Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakao
authors.affiliation: Fukui Institute for Fundamental Chemistry, Kyoto University , Nishihiraki-cho, Takano, Sakyo-ku, Kyoto 606-8103, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Sakaki
authors.affiliation: Department of Chemistry, Dr. Harisingh Gour Central University , Sagar 470003, India.
authors.forename: Milind M
authors.identifier: 0000-0003-3518-7859
authors.initials: MM
authors.lastname: Deshmukh