Experimental and computational insights into the mechanism of FLP mediated selective C-F bond activation

Frustrated Lewis pairs (FLP) comprising of B(C₆F₅)₃ (BCF) and 2,4,6-triphenylpyridine (TPPy), P(o-Tol)₃ or tetrahydrothiophene (THT) have been shown to mediate selective C-F activation in both geminal and chemically equivalent distal C-F sites. In comparison to other reported attempts of C-F activation using BCF, these reactions appear surprisingly facile. We investigate this reaction through a combination of experimental and computational chemistry to understand the mechanism of the initial C-F activation event and the origin of the selectivity that prevents subsequent C-F activation in the monoactivated salts. We find that C-F activation likely occurs via a Lewis acid assisted S_N1 type pathway as opposed to a concerted FLP pathway (although the use of an FLP is important to elevate the ground state energy), where BCF is sufficiently Lewis acidic to overcome the kinetic barrier for C-F activation in benzotrifluorides. The resultant intermediate salts of the form [ArCF₂(LB)][BF(C₆F₅)₃] (LB = Lewis base) are relatively thermodynamically unstable, and an equilibrium operates between the fluorocarbon/FLP and their activation products. As such, the use of a fluoride sequestering reagent such as Me₃SiNTf₂ is key to the realisation of the forward C-F activation reaction in benzotrifluorides. Selectivity in this reaction can be attributed to both the installation of bulky Lewis bases geminal to residual C-F sites and from electronic re-ordering of kinetic barriers (of C-F sites in products and starting materials) arising from the electron withdrawing nature of the pyridinium, phosphonium and sulfonium groups.