Effective production of selected dioxolanes by sequential bio- and chemocatalysis enabled by adapted solvent switching.

Most combinations of chemo- and biocatalysis take place in aqueous media or required a solvent change with complex intermediate processing. Using enzymes in the same organic solvent as the chemocatalyst eliminates this need. Here we show, that a complete chemoenzymatic cascade to form dioxolane can be carried out in a purely organic environment. We compare the result, including downstream processing, with a classical mode, shifting solvent. First, a two-step enzyme cascade starting from aliphatic aldehydes to chiral diols (3,4-hexanediol and 4,5-octanediol) is run either in an aqueous buffer or in the biobased solvent cyclopentyl methyl ether. Subsequently, a ruthenium molecular catalyst enables the conversion to dioxolanes, e.g. (4S,5S)-dipropyl-1,3-dioxolane. Importantly, the total synthesis of this product is not only highly stereoselective, but also based on the combination of biomass, CO2 and hydrogen, thus providing an important example of a bio-hybrid chemical.