Substrate Facilitating Roles in Rare-Earth-Catalyzed C-H Alkenylation of Pyridines with Allenes: Mechanism and Origins of Regio- and Stereoselectivity

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.