tBu or not tBu?

Graphical Abstract

A Hamlet study: The regioselectivity in the palladium-catalyzed Heck reaction between an aryl halide and ethyl vinyl ether with different phosphine ligands PPh_ntBu_m (n=0–3, m=3−n) has been investigated both experimentally and computationally. The number m of tBu groups (see picture) in the ligand is found to strongly influence the regioselectivity, and the different transition states involved in this study are demystified.

Abstract

The regioselectivity in the palladium-catalyzed Heck coupling reaction between an aryl halide and ethyl vinyl ether with four different phosphine ligands: PPh_ntBu_m (n=0–3, m=3−n) has been investigated both experimentally and computationally. A zigzag selectivity pattern was experimentally observed upon consecutive replacement of Ph by tBu in the phosphine ligand. Use of a standard DFT method (B3LYP) was shown to give a correct prediction of product preference. However, the trend in relative selectivity among the different ligands could not be correctly described. The use of a more recent DFT functional (M06) parameterized to reproduce dispersion interactions resulted in an improved description. For the sterically most demanding ligands, PtBu₃ and PPhtBu₂, unexpectedly large deviations between experimental and M06 calculated selectivities raised the question of an alternative mechanism for these ligands. In the case of PtBu₃ it was found, in agreement with literature data, that the phosphine ligand could be replaced by a second halide ligand, resulting in an anionic mechanism, with a calculated selectivity in excellent agreement with experimental data. For the PPhtBu₂ ligand, two mechanisms are suggested to operate in parallel, as demonstrated both by computational studies and experimental observation of halide-dependent selectivity. A Halpern effect is observed for all phosphine ligands investigated, that is, the least stable pre-complex results in the most abundant product.