Mechanisms of Csp3-H functionalization of acetonitrile or acetone with coumarins: A DFT investigation

Abstract

The mechanisms for the cross-dehydrogenative coupling (CDC) between coumarin and acetonitrile (or acetone) have been investigated with M06-L-D3 method, and 6−31+G(d,p) basis set for nonmetal elements and pseudopotential basis set of SDD for potassium atom. SMD model was applied to simulate the solvent effect. The computational results show that tert-Butyl peroxybenzoate (TBPB) is the best oxidant with the lowest bond dissociation Gibbs free energy (BDE=11.2 kcal/mol in the solvent of acetonitrile) and could be easily disintegrated into two radicals (PhCOO and t-BuO). In the first and second reactions, 2H-chromen-2-one reacted with acetontrile and acetone, respectively. Firstly, the Csp3-H activations of acetontrile and acetone could be achieved by PhCOO and t-BuO radicals; then cross-dehydrogenative coupling reactions converted 2H-chromen-2-one into final products P1 and P2; Gibbs free energy surfaces of these two reactions suggest that paths a4 and b4 would be the favorable paths with lower Gibbs energy barriers and releasing much energy. While in the third reaction, acetonitrile reacted with (E)-4-phenylbut-3-en-2-one via six possible paths, and path c4 could be the favorable one. When radical scavenger BHT (butylated hydroxytoluene) was added into the first reaction, only fourth product P4 can be yielded. The Gibbs free energy surface analysis of fourth reaction shows that BHT is much active than acetonitrile to go through the Csp3-H activation and path d2 is the favorable, which can agree with the experimental results. The BDE, localized orbital locator (LOL) isosurfaces, Laplacian bond order (LBO), electron density of bond critical point (ρBCP) and electron spin density isosurface graphs can be used to analyze the structure and reveal the reaction substances.