Transition Metal-Free Direct Hydrogenation of Esters via a Frustrated Lewis Pair

“Frustrated
Lewis pairs” (FLPs) continue to exhibit
unique reactivity for the reduction of organic substrates, yet to
date, the catalytic hydrogenation of an ester functionality has not
been demonstrated. Here, we report that iPr3SnNTf2 (1-NTf2; Tf = SO2CF3) is a more potent Lewis acid than the previously studied iPr3SnOTf; in an FLP with 2,4,6-collidine/2,6-lutidine (col/lut),
this translates to faster H2 activation and the catalytic
hydrogenolysis of an ester bond by a main-group compound, furnishing
alcohol and ether (minor) products. The reaction outcome is sensitive
to the steric and electronic properties of the substrate; CF3CO2Et and simple formates (HCO2Me and HCO2Et) are catalytically reduced, whereas related esters CF3CO2nBu and CH3CO2Et show only stoichiometric reactivity. A computational case
study on the hydrogenation of CF3CO2Et and CH3CO2Et reveals that both share a common mechanistic
pathway; however, key differences in the energies of a Sn-acetal intermediate
and transition states emerge, favoring CF3CO2Et reduction. The alcohol products reversibly inhibit 1-NTf2/lut via formation of resting-state species 1-OR/[1·(1-OR)]+[NTf2]−; however, the extra energy required
to regenerate 1-NTf2/lut exacerbates the unfavorable
reduction energy profile for CH3CO2Et, ultimately
preventing turnover. These findings will assist the design of future
main-group catalysts for ester hydrogenation, with improved performance.