From a Sequential to a Concurrent Reaction in Aqueous Medium: Ruthenium‐Catalyzed Allylic Alcohol Isomerization and Asymmetric Bioreduction

Abstract

The ruthenium-catalyzed redox isomerization of allylic alcohols was successfully coupled with the enantioselective enzymatic ketone reduction (mediated by KREDs) in ac oncurrent process in aqueous medium. The overall transformation, formally the asymmetric reduction of allylic alcohols,t ook place with excellent conversions and enantioselectivities,u nder mild reaction conditions,e mploying commercially and readily available catalytic systems,a nd without external coenzymes or cofactors.O ptimization resulted in amultistep approachand agenuine cascade reaction where the metal catalyst and biocatalyst coexist from the beginning.

Chemoenzymatic Cascades Combining Biocatalysis and Transition Metal Catalysis for Asymmetric Synthesis

“…A commercial ATA, PLP and additional buffer were added to carry out the transamination, successfully isolating the desired optically active amines. The same research group published a similar strategy replacing ATAs by commercial ADHs for the synthesis of chiral alcohols in a concurrent cascade approach [36] . Both the isomerization of the starting allylic alcohols and the bioreduction were performed at 30 °C, obtaining the enantiopure alcohols with variable yields (Scheme 7B).…”

The various levels of integration of chemo- and bio-catalysis towards hybrid catalysis

“…94,116,117 Metals can catalyze many types of reactions and are active in aqueous medium, making them good candidates for the implementation of hybrid processes with a wide variety of enzymes. 106,[118][119][120][121] Finally, the material on which to immobilize the catalysts must be considered. Various solid particles can be used to manufacture biohybrid catalysts, ranging from silica to reduced graphene oxide to a polymer matrix composite.…”

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

“…This may be attributed to broad substrate scope of the oxidases, which use molecular oxygen as the electron acceptor without co‐factors and recycling systems, showing great potential for practical applications. While transition metal catalysts have been broadly used under biologically relevant conditions, [33–37] sequential or tandem cascades incorporating organic and biological systems provide new solutions to access challenging transformations in aqueous phase and under mild conditions [38]…”