Abstract
The combination of bio- and chemo-catalytic processes has tremendous potential for the sustainable production of important synthetic building blocks. Such approaches capitalize on the often-high selectivity of enzymes and the broad arsenal of synthetic transformations to access highly functionalized molecules from simple precursors. However, the strict requirement of enzymes for an aqueous reaction environment, often combined with their lack of stability under harsh reaction conditions, makes the development of efficient chemo-enzymatic cascade reactions challenging. Within this work, we developed a chemo-enzymatic platform that combines regioselective enzymatic Halogenation, chemo-catalytic Heck coupling, and an enzyme-catalyzed Hydrolysis reaction (H(3) Catalytic Platform = H(3)CP) in a single reaction vessel. H(3)CP uses water as a reaction solvent to facilitate the enzymatic transformations, with the cross-coupling reaction taking place in dynamic and protective super-molecular reaction vessels composed of the commercially available TPGS-705-M. Our work utilizes various halogenating enzymes (FDHs and VHPOs), selectively functionalizing diverse substrates, thus enabling subsequent metal-catalyzed cross-coupling followed by enzymatic hydrolysis. H(3)CP gives access to a broad range of valuable acrylic acid building blocks with diverse functionalization at the aromatic portion.