Comparison between Chemoenzymatic and Bienzymatic Cascades Leading to Morita–Baylis–Hillman Adducts

Abstract Chemoenzymatic and bienzymatic cascades offer advantages including increasing diversity of reactions and saving time and operational costs. Herein the oxidation of benzylic alcohols to the corresponding aldehydes coupled with the Morita−Baylis−Hillman (MBH) reactions in biocatalytic compatible potentially ‘green’ conditions has been exemplarily evaluated. One‐pot cascades avoiding the use of reactive aldehyde intermediates are described and compared, including a sequential chemoenzymatic cascade with a variant of galactose oxidase (GOase M 3–5 ) and 1,4‐Diazabicyclo [2.2.2] octane (DABCO), a concurrent dual‐enzyme cascade with GOase M 3–5 and a variant of the computationally designed enzyme MBHase (BH32.14), and finally a whole cell biotransformation with the co‐expression modules of the two enzymes. All of the cascades were performed on a diverse range of substrates (12–19 examples), affording moderate to high conversions (up to 93 %) and isolated yields (up to 80 %). The bienzymatic cascades offer optically active products in up to 91 % ee. Key factors affecting the chemoenzymatic and the bienzymatic cascades were highlighted, and the advantages and challenges were compared.