The alkene insertion via the heteroatom-containing substrate facilitated mechanism were computationally revealed in rare-earth-catalyzed C–H alkylation of sulfides and other heteroatom-containing substrates such as pyridines and anisoles.

Benzylic C(sp 3 )−H alkylation of tertiary anilines with alkenes by an anilido-oxazoline-ligated scandium alkyl catalyst was recently reported with C−H site selectivity and alkenedependent regioselectivity. Revealing the mechanism and origin of selectivity is undoubtedly of great importance for understanding experimental observations and developing new reactions. Herein, density functional theory (DFT) calculations have been carried out on the model reaction of Sc-catalyzed benzylic C(sp 3 )−H alkylation of N,N-dimethyl-o-toluidine with allylbenzene. The reaction generally undergoes the generation of active species, alkene insertion, and protonation steps. The difference of the distortion energy of the aniline moiety in transition states, which is related to the ring size of the forming metallacycles, accounts for the site selectivity of C−H activation. Benzylic C(sp 3 )−H activation possessing less strained five-membered metallacycle compared to the ortho-C(sp 2 )−H and α-methyl C(sp 3 )−H activation results in benzylic C(sp 3 )−H alkylation observed experimentally. Both steric and electronic factors are responsible for the 1,2-insertion regioselectivity for alkyl-substituted alkenes, while electronic factors control the 2,1-insertion manner for vinylsilanes. The analysis of original alkene substrates further strengthens the understanding of the alkene-dependent regioselectivity. These results help us to obtain the mechanistic understanding and are expected to be conducive to the development of new C−H functionalization reactions.

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.