Methods, reactor systems, and catalysts are provided for converting in a continuous process biomass to fuels and chemicals, including methods of converting the water insoluble components of biomass, such as hemicellulose, cellulose and lignin, to volatile C2+O1-2 oxygenates, such as alcohols, ketones, cyclic ethers, esters, carboxylic acids, aldehydes, and mixtures thereof. In certain applications, the volatile C2+O1-2 oxygenates can be collected and used as a final chemical product, or used in downstream processes to produce liquid fuels, chemicals and other products.