Electrospray (ES) and paper spray (PS) mass spectrometry were used to create confined liquid volumes in which accelerated air and water sensitive, heterogeneous, copper catalysed C–O and C–N coupling reactions occur. Significant reaction acceleration was observed compared to the bulk reaction which required elevated temperatures and time for completion. Macroscopic amounts of product (mg scale) were prepared using offline ES within minutes. The trends in reactivity observed for several reagents matched those of the bulk reactions making droplet accelerated reactions good mimics of the bulk chemistry.