A Bifurcating Chemoenzymatic Domino Knoevenagel-acylation/Hydrolysis-Protonolysis Three-component Synthesis of alpha-Cyano (Hetero)aryl Acrylates and/or Amides

摘要

Methyl alpha-cyano beta-(hetero)aryl acrylates are excellent substrates for CAL-B catalyzed aminolyses. However, upon concatenation of the substrate Knoevenagel condensation (of (hetero) aryl carbaldehydes and methyl cyano acetate) and the CAL-B catalyzed aminolysis, an interesting bifurcating domino Knoevenagel-CAL-B catalyzed aryl methylaminolysis/hydrolysis reaction furnishing either amides or salts in the sense of a three-component process was found. The enzyme mediated acylative bifurcation of water vs benzyl amines depends on the substitution pattern of the aldehydes and on the presence or absence of a water scavenger. In the former case, amidation is favored while in the latter case hydrolysis/salt formation prevails.