Theoretical study on the base-controlled selective linear or branched ortho-alkylation of azines catalyzed by rhodium: Mechanisms and the role of base

Abstract

The detailed theoretical study on the mechanism of the alkylation of 3-trifluoromethylpyridine with acrylamide in the [RhI]/dppe catalytic system is reported, with the aid of the density functional theory (DFT) calculations. It is found that the additive bases play a critical role in switching the regioselectivity. The origin of the regioselectivity involved in these reactions was probed by performing distortion-interaction analysis. For reaction A with KOPiv as the base, the outer-sphere concerted-metallative-deprotonation (CMD) pathway is calculated to be a bit more favorable kinetically compared with the oxidative addition (OA) one and the two mechanisms are competitive. The regioselectivity in this reaction is predicted to be determined by the distortion energies of the migratory insertion transition states. In contrast, for reaction B with K3PO4 as the base, the feasible pathway is the OA one, and the corresponding interaction energies for the olefin migratory insertion into Rh–H bond step could account for the observed regioselectivity.