Mechanistic investigation into Et3N C-H activation and chemoselectivity by Pd-Catalyzed intramolecular heck reaction of N-Vinylacetamides

Density functional theory (DFT) calculations have been conducted to elucidate the detailed mechanism of Pd-Catalyzed intramolecular Heck reaction of N-vinylacetamides. Pd(PPh3)(2) and (PPh3)PdOAc-, generated in situ from Pd(OAc)(2)/PPh3, are predicted to be the active Pd(0) catalyst. The reaction undergoes C(aryl)-Br oxidative addition, alkene insertion, beta-N group elimination, and nitrogen protonation. The C-H activation of Et3N, which is requisite for nitrogen protonation, was explored emphatically. An ion-pair intermediate containing both an anionic Pd(II) complex (a 16e 4-coordinate square planar structure) and a cationic moiety Et2N=CHCH3+ was found to be involved in the C-H activation. The nitrogen atom of Et3N plays a crucial role in stabilizing the cationic moiety by means of its lone pair to afford a N=C double bond, and thus ruling out the possibility of the beta-C-H bond activation. Additionally, the high chemoselectivity for P1 rather than P2 and P3 were rationalized theoretically. (C) 2016 Elsevier B.V. All rights reserved.