Autothermal partial oxidation is a promising technique to upgrade bio-oil into syngas and commodity chemicals. This work aims to clarify preferred chemical routes in an autotherrnal system by investigating individually two-carbon molecules containing the functional groups found in bio-oil. Acids, alcohols, aldehydes, esters, ethers, and polyols were reacted over Pt- and Rh-Al2O3 catalysts. Also, to investigate thermal effects independent of O-2-induced reactions, these molecules were passed over the same catalysts under similar conditions but in the absence of O-2. Oxygen and adsorption geometry (the latter deduced from surface science literature) appear to play a key role in reaction initiation (manifested via overall conversion) and in the subsequent reaction of intermediate compounds. The catalyst identity also played a significant role in the observed product spectrum, and conversion was higher over the Rh catalyst. Polyols, ethers, and acids were the least reactive, while esters were the most reactive. The Rh catalyst yielded slightly higher selectivity to syngas products, while the Pt catalyst yielded slightly higher selectivity to combustion and intermediate products. Product selectivities and the surface science literature are used to propose reaction pathways.