On the possibility of catalytic reduction of carbonyl moieties with tris(pentafluorophenyl)borane and H-2: a computational study

The study thoroughly examines the Gibbs free energy surfaces of a new mechanism for reduction of ketones/aldehydes by tris(pentafluorophenyl) borane (1) and H-2. Key elements of the proposed mechanism are the proton and the hydride transfer steps similar to Stephan's catalytic reduction of imines by 1. The proton is transferred to the ketone/aldehyde in the process of H-2 cleavage by the carbonyl-borane couple and the hydride is transferred in a nucleophilic attack on the carbonyl carbon by the hydridoborate in the ionic pair, [HOCRR']+[HB(C6F5)(3)](-). The in solvent Gibbs free energy barriers of H2 splitting by adducts of B(C6F5)(3) with acetone, acetophenone and benzaldehyde are predicted to be in the range of 24.5 +/- 2.5 kcal mol(-1), which corresponds to potential energy barriers in the range of 17.0 +/- 2.0 kcal mol(-1). Significantly lower barrier of H-2 activation is predicted in cases of bulky ketones such as 2,2,4,4-tetramethylpentan-3-one. With respect to the hydridoborate intermediate, the nucleophilic attack on the activated carbon is predicted to have a relatively low barrier for the sterically unhindered substrates, while this barrier is considerably higher for the sterically encumbered substrates. Since the formation of the hydridoborate intermediates is found to be endothermic, the transition state of the nucleophilic attack is the highest point of the computed energy pro. le for all tested substrates. Overall, according to in solvent density function calculations the proposed reduction of compact ketones/aldehydes by 1 and H-2 is allowed both thermodynamically and kinetically at elevated temperature, but it is expected to be slower and more substrate specific than the corresponding reduction of imines.