Exploiting the Liquid Phase to Enhance the Cross-Coupling of Alcohols over Nanoporous Gold Catalysts

The control of selectivity in the cross-coupling of two similar compounds is a classic challenge in heterogeneous catalysis. Here, it is shown that the phase in which the catalysis is performed has a dramatic impact on the selectivity of the oxidative coupling of alcohols to esters over unsupported nanoporous gold catalysts, affording nearly optimal cross-coupling to a single ester at equimolar concentrations in the liquid. Operation in the liquid vs the gas phase affects (1) the relative C–H activation rates of methoxy and 1-propoxy, (2) the fraction of C–H activation which leads to esters vs aldehydes, and (3) the fraction of esters which results from cross-coupling vs self-coupling. While activation of the critical, adsorbed alkoxy intermediate 1-propoxy is faster than methoxy in both phases of operation, the liquid phase is more effective in coupling the resulting aldehyde with adsorbed methoxy or 1-propoxy to yield an ester. Additionally, operation in the liquid phase promotes cross-coupling to methyl propionate, whereas in the gas-phase, self-coupling of 1-propanol to propyl propionate is favored. The promotion of self-coupling in the gas phase results from the stabilization of larger alkoxides on the surface by Au-alkyl van der Waals forces. However, such forces do not appear to be dominant in the liquid phase, as evidenced by similar cross-coupling selectivities of methanol with ethanol, 1-propanol, and 1-butanol. The introduction of steric hindrance into the higher alcohol (i.e., 2-methyl-1-propanol) further promotes cross-coupling. This promotion is attributed to a kinetic preference for an aldehyde to couple with less-hindered alkoxides. Altogether, these findings demonstrate that alcohol cross-coupling selectivities are strongly impacted by the phase in which the catalysis is conducted, thus altering the phase provides opportunities for selective and efficient chemical syntheses.