Organocatalytic C−F Bond Activation with Alanes

Abstract

Hydrodefluorination reactions (HDF) of per- and polyfluorinated olefins and arenes by cheap aluminum alkyl hydrides in non-coordinating solvents can be catalyzed by O and N donors. TONs with respect to the organocatalysts of up to 87 have been observed. Depending on substrate and concentration, high selectivities can be achieved. For the prototypical hexafluoropropene, however, low selectivities are observed (E/Z≈2). DFT studies show that the preferred HDF mechanism for this substrate in the presence of donor solvents proceeds from the dimer Me Al (μ-H) ⋅THF by nucleophilic vinylic substitution (S V)-like transition states with low selectivity and without formation of an intermediate, not via hydrometallation or σ-bond metathesis. In the absence of donor solvents, hydrometallation is preferred but this is associated with inaccessibly high activation barriers at low temperatures. Donor solvents activate the aluminum hydride bond, lower the barrier for HDF significantly, and switch the product preference from Z to E. The exact nature of the donor has only a minimal influence on the selectivity at low concentrations, as the donor is located far away from the active center in the transition states. The mechanism changes at higher donor concentrations and proceeds from Me AlH⋅THF via S V and formation of a stable intermediate, from which elimination is unselective, which results in a loss of selectivity.

Gallium Hydrides and O/N‐Donors as Tunable Systems in C−F Bond Activation

“…the thermodynamically more stable E ‐isomer of 1,3,3,3‐tetrafluoropropene ( 5 b ) is preferentially formed. Such a high E / Z ratio is not observed in titanium‐, rare‐earth‐metal‐catalyzed or alane‐induced HDF reactions; a maximum E / Z ratio of 15 has been reported . Conversions of the HDF reactions with 1 a in diglyme and NEt 3 are similar (53–56 %, entry 2,3), but the selectivity is much higher when the reaction is conducted in NEt 3 .…”

“…Recent studies towards aluminum hydrides in C‐F bond activation reactions showed that their reaction behavior coincide with the gallium hydrides. No or almost no HDF products could be observed for the HDF reactions with ( i Bu) 2 AlH ( 2 a ) or LiAlH 4 ( 2 b ) in toluene, but addition of catalytic amounts of donor molecules lead to high conversions (Table ). Comparison of the gallium hydrides 1 a and 1 b with corresponding aluminum hydrides 2 a and 2 b demonstrate that the reaction behavior of the ionic compounds 1 b and 2 b are similar: in the non‐coordinating solvent toluene the conversion is low, but addition of 10 mol % diglyme increases the conversion up to 100 % for 3 , 4 f and 7 (compare Table – with ).…”

“…Monomer–dimer–donor equilibria . We have recently shown that HDF using aluminum hydrides and O or N donors proceeds via the aluminum dimer donor adduct . The donor is located far away from the active center in the TS and the exact nature of the donor thus does not influence the selectivity of the HDF reaction.…”

“…To model the HDF reaction by computational chemistry, we chose 4 f , the gallium hydride HGaMe 2 ( 1M ) and the donor THF. The Gibbs free energy of two molecules 1M forming the gallium hydride dimer 1D is predicted to be 18.4 kcal mol −1 or ≈7 kcal mol −1 lower than for the corresponding aluminum compound (Scheme ) . Additionally, THF binds only very weakly to the dimer 1D (−0.6 kcal mol −1 ), forming 1D‐THF .…”

“…In continuation of our studies concerning the organocatalytic hydrodefluorination (HDF) of several olefinic and aromatic fluorinated compounds with aluminum hydrides, we were interested in exploring the reactivity of gallium hydrides for C−F bond activation.…”