A Strategy for C−H Activation of Pyridines:  Direct C-2 Selective Alkenylation of Pyridines by Nickel/Lewis Acid Catalysis

Abstract

The C-2 selective alkenylation of pyridine derivatives is achieved with a catalyst consisting of nickel and Lewis acid. Use of diorganozinc compounds as the Lewis acid catalyst gives C-2 monoalkenylation products, whereas AlMe3 changes the reaction course to afford C-2 dienylated products, which are derived from double insertion of alkynes into the C(2)−H bond. The reaction demonstrates a broad substrate scope and proceeds with high chemo-, regio-, and stereoselectivities under mild conditions compared with previous examples of direct C−H functionalization of pyridines.

Recent advances on nickel-catalyzed C–H bonds functionalized reactions

“…This study reveal that Lewis acid plays a critical role in activating the formamides towards C(sp 2 )-H activation. 29,30 With this Lewis-acid assistance, [Ni] oxidatively adds the C(sp 2 )-H bond of the formamide. Alkyne insertion followed by C-C bond-forming reductive elimination provides highly substituted acrylamides.…”

C–H Bond Alkenylation

“…Nakao, Hiyama, and coworkers [93] succeeded in applying their Ni catalyst to the C2-alkenyation of pyridines (Scheme 18.91). Addition of the Lewis acid such as ZnPh 2 is key to conduct the reaction efficiently.…”

Progress of Cooperative Catalysis in Organic Synthesis

“…同样, 利用过渡金属催化的炔的胺化反应, 刘学伟 研究组 [6] 报道了以 Cu(OAc) 2 [7] . Nakao 研究组 [8] 曾报道了利用金属 Ni 和 Zn(Me) 2 [12,13] 、Ir-Ru 共催化 [14] 、Au-Ag 共催化 [15] 、 Co-Ti 共催化 [16] 、Ni-Al 共催化、Ru-Pd 共催化 [17] 等体系 在有机合成中都有很好的应用.…”