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

Frustrated Lewis pairs (FLP) comprising of B(C(6)F(5))(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(N)1 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 [ArCF(2)(LB)][BF(C(6)F(5))(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 Me(3)SiNTf(2) 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.