Synthesis of 3‐Arylated 3,4‐Dihydrocoumarins: Combining Continuous Flow Hydrogenation with Laccase‐Catalysed Oxidation

Abstract

Abstract A convenient arylation of diverse 3,4‐dihydrocoumarins with a number of catechols is described leading to a new class of compounds. As key step, a laccase‐catalysed oxidation/Michael addition sequence is applied using commercially available laccase from Agaricus bisporus . 3,4‐Dihydrocoumarins were obtained in a rapid and facile two‐step sequence starting from salicylaldehydes: The corresponding coumarins were synthesised through a Knoevenagel condensation in up to 83% yield followed by a quantitative reduction performed in a flow system. Combining the reductive flow reaction with the laccase‐catalysed arylation also led to successful consecutive one‐pot approaches. Overall, the enzyme‐catalysed arylations were carried out with yields ranging from 63 to 94%. magnified image