Electrostatic vs. inductive effects in phosphine ligand donor properties and reactivity

Abstract

Enhanced rates and selectivity in enzymes are enabled in part by precisely tuned electric fields within active sites. Analogously, the use of charged groups to leverage electrostatics in molecular systems is a promising strategy to tune reactivity. However, separation of the through space and through bond effects of charged functional groups is a long standing challenge that limits the rational application of electric fields in molecular systems. To address this challenge we developed a method using the phosphorus selenium coupling value (J_P–Se) of anionic phosphine selenides to quantify the electrostatic contribution of the borate moiety to donor strength. In this analysis we report the synthesis of a novel anionic phosphine, PPh₂CH₂BF₃K, the corresponding tetraphenyl phosphonium and tetraethyl ammonium selenides [PPh₄][SePPh₂CH₂BF₃] and [TEA][SePPh₂CH₂BF₃], and the Rh carbonyl complex [PPh₄][Rh(acac)(CO)(PPh₂(CH₂BF₃))]. Solvent-dependent changes in J_P–Se were fit using Coulomb's law and support up to an 80% electrostatic contribution to the increase in donor strength of [PPh₄][SePPh₂CH₂BF₃] relative to SePPh₂Et, while controls with [TEA][SePPh₂CH₂BF₃] exclude convoluting ion pairing effects. Calculations using explicit solvation or point charges effectively replicate the experimental data. This J_P–Se method was extended to [PPh₄][SePPh₂(2-BF₃Ph)] and likewise estimates up to a 70% electrostatic contribution to the increase in donor strength relative to SePPh₃. The use of PPh₂CH₂BF₃K also accelerates C–F oxidative addition reactivity with Ni(COD)₂ by an order of magnitude in comparison to the comparatively donating neutral phosphines PEt₃ and PCy₃. This enhanced reactivity prompted the investigation of catalytic fluoroarene C–F borylation, with improved yields observed for less fluorinated arenes. These results demonstrate that covalently bound charged functionalities can exert a significant electrostatic influence under common solution phase reaction conditions and experimentally validate theoretical predictions regarding electrostatic effects in reactivity.