A chemoenzymatic microfluidic cascade reaction is demonstrated for the first time, where a Diels-Alder
reaction is followed by a transketolase reaction, for the synthesis of 3,4-dimethylcyclohex-3-ene-2’-keto-1’,3’-
propanediols, which are used as scaffolds for a number of interesting pharmaceutical compounds. For an efficient
organic synthesis, an enzymatic reaction would be advantageous, as it would minimize the number of process steps
by eliminating the need for protective chemistry [1]. However, most catalysts and reactions conditions used with
DA reactions are not compatible with a subsequent enzymatic reaction (issues revolve e.g. around solvent
compatibility, differing reaction rates, and mis-match of pH). We used the spatial confinement of reactions afforded
by cascaded microreactors, which has been well established for enzyme-enzyme reactions [2], to overcome these
challenges and to achieve a chemoenzymatic reaction in continuous flow. Each reaction was optimized individually
or in a step-wise synthesis, considering solvents and catalyst combinations, before being coupled in continuous
flow
