Development of the self-assembled monolayer/MALDI mass spectrometry (SAMDI) platform to enable a high-throughput optimization of a traceless Petasis reaction is described. More than 1800 unique reactions were conducted simultaneously on an array of self-assembled monolayers of alkanethiolates on gold to arrive at optimized conditions, which were then successfully transferred to the solution phase. The utility of this reaction was validated by the efficient synthesis of a variety of di- and trisubstituted allenes.