we reportthat N,N-dimethylacetamide (DMA) containing lithium chloride (LiCl) is a privileged solvent that enablesthe synthesis of the renewable platform chemical 5-hydroxymethylfurfural (HMF) in a single step andunprecedented yield from untreated lignocellulosic biomass, as well as from purified cellulose, glucose,and fructose. The conversion of cellulose into HMF is unabated by the presence of other biomasscomponents, such as lignin and protein. Mechanistic analyses reveal that loosely ion-paired halide ions inDMA-LiCl are critical for the remarkable rapidity (1-5 h) and yield (up to 92%) of this low-temperature(e140 °C) process. The simplicity of this chemical transformation of lignocellulose contrasts markedly withthe complexity of extant bioprocesses and provides a new paradigm for the use of biomass as a raw materialfor a renewable energy and chemical industries.