Achieving high selectivity for high volume chemical synthesis is important for lowering energy consumption through reduction in waste. We report the selective synthesis of methyl esters-methyl acetate and methyl butyrate-through catalytic O-2-assisted cross-coupling of methanol with ethanol or 1-butanol using activated, support-free nanoporous gold (npAu). Both well-controlled studies on ingots in UHV and experiments under ambient pressure catalytic conditions on both ingots and microspherical hollow shell catalysts reveal guiding principles for controlling selectivity. Under UHV conditions, the ester products of the cross-coupling of methanol with both ethanol and 1-butanol evolve near room temperature in temperature-programmed reaction studies, indicating that the reactions occur facilely. Under steady-state catalytic operation, high stable activity was observed for cross-coupling in flowing gaseous reactant mixtures at atmospheric pressure and 423 K with negligible combustion. Optimum selectivity for cross-coupling is obtained in methanol-rich mixtures due to a combination of two factors: (1) the relative coverage of the respective alkoxys and (2) the relative facility of their beta-H elimination. The relative coverage of the alkoxys is governed by van der Waal's interactions between the alkyl groups and the surface; here, we demonstrate the importance of these weak interactions in a steady-state catalytic process. (C) 2015 Elsevier Inc. All rights reserved.