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 require a solvent change with complex intermediate processing. Using enzymes in the same organic solvent as the chemocatalyst eliminates this need. Here, it was shown that a complete chemoenzymatic cascade to form dioxolanes could be carried out in a purely organic environment. The result, including downstream processing, was compared 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) was run either in an aqueous buffer or in the potentially biobased solvent cyclopentyl methyl ether. Subsequently, a ruthenium molecular catalyst enabled the conversion to dioxolanes [e. g., (4S,5S)‐dipropyl‐1,3‐dioxolane]. Importantly, the total synthesis of this product was 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. A winning combination: The combination of bio‐ and chemocatalysis is a powerful method to access complex (chiral) molecules. Here, a 2‐step enzymatic cascade is combined in the same organic solvent with a ruthenium‐catalyzed chemical conversion to form dioxolanes from aliphatic aldehydes. The method of combining the two worlds can be applied easily to other hybrid systems.