Substrate Facilitating Roles in Rare-Earth-Catalyzed C–H Alkenylation of Pyridines with Allenes: Mechanism and Origins of Regio- and Stereoselectivity
Ping Wu, Fanshu Cao, Yu Zhou, Zuqian Xue, Ni Zhang, Lei Shi, Gen Luo
Abstract
Although considerable progress has been achieved in C–H functionalization by cationic rare-earth alkyl complexes, the potential facilitating roles of heteroatom-containing substrates during the catalytic cycle remain highly underestimated. Herein, theoretical studies on the model reaction of C(sp2)–H addition of pyridines to allenes by scandium catalyst were carefully carried out to reveal the detailed mechanism. A coordinating pyridine substrate as a ligand can effectively stabilize some key structures. An obvious facilitating role delivered by the coordinating pyridine was found for allene insertion, while the pyridine-free mechanism prefers to occur for C(sp2)–H activation processes. Importantly, the elusive role of heteroatom-containing substrates was systematically revealed for the C–H activation event by designing a metal/ligand combination of catalysts and substrates. We found that the pyridyl C(sp2)–H activation would be switched to the pyridine-coordinated mechanism in the cases of the designed Y and La catalysts. To date, this is the first time to realize the potential substrate-facilitating role in cationic rare-earth-catalyzed C–H activation processes. Moreover, theoretical predictions show that similar switchable mechanisms also work for other types of C–H bonds and other heteroatom-involved substrates by fine-adjusting the steric surroundings of catalysts. The two C–H activation mechanisms are mainly the result of the delicate balance between electronic and steric factors. In general, the catalytic system with less steric hindrance prefers to undergo the substrate-coordinated mechanism. In contrast, the substrate-free mechanism is favorable due to steric repulsion. These results are helpful for us to better understand the variant mechanisms in rare-earth-catalyzed C–H functionalization at the atomistic level and may help guide the rational design of new catalytic reactions. In addition, the origins of the regio- and stereoselectivity were discussed through geometric parameters and distortion/interaction analysis.