Theoretical study on β-H elimination in Heck reactions of heterocyclic substrates

β-Arylation of thiophenes might proceed through the Heck mechanism, but in this system the syn-βH elimination of conventional Heck mechanism could not take place. To understand the H elimination in Heck reactions of substituted thiophenes without syn-βH, three mechanistic possibilities, i.e. isomerization and syn-βH elimination (Mechanism A), αH elimination and 1,2-H shift (Mechanism B), and anti-βH elimination (Mechanism C), were carefully examined by DFT methods. More importantly, various factors (substrates, ligands and bases) on these βH elimination processes were systematically analyzed, as they might control the barriers of different hydrogen elimination. Based on the calculations, we found that base-assisted anti-βH elimination is the most energetically favored in the Heck hydrogen elimination mechanisms in substituted thiophenes systems as well as other heterocycles (i.e. thiophene, furan and N-methylpyrrole). Moreover, isomerization and syn-βH elimination (Mechanism A) may also be taken into account on the condition that the substrate has a weakly acidic α-hydrogen and no substituent on the heteroatom. In addition, the phosphine ligands with different electron-donating abilities have no effect on the preferred anti-βH elimination mechanism. Finally, carbonate as the base employed in Heck reaction is more beneficial for the anti-βH elimination than the amine. These results could not only offer a more comprehensive understanding of the Heck mechanism, but also provide helpful insights to the development of Heck-type arylation reactions of heterocyclic substrates.