Chemoenzymatic Cascades Combining Biocatalysis and Transition Metal Catalysis for Asymmetric Synthesis

Abstract

The combination of catalytic methods provides multiple advantages in organic synthesis, allowing access to diverse organic molecules in a straightforward manner. Merging metal and enzyme catalysis is currently receiving great attention due to the possibility to assemble metal catalysis in C−C coupling, olefin metathesis, hydration and other reactions with the exquisite stereospecificity displayed by enzymes. Thus, this minireview is organized based on the action of the metal species (Pd, Ru, Au, Ir, Fe…) in combination with different enzymes. Special attention will be paid to the design of sequential processes and concurrent cascades, presenting solutions such as the use of surfactants or compartmentalization strategies for those cases where incompatibilities could hamper the overall process.

Organocatalytic hydration of activated alkynes

“…The main advantage of this strategy is that it enables the construction of synthetic complexity with simpler setups. (45)(46)(47)(48)(49) With our broad experience in the construction of chemoenzymatic cascades by merging chemical and enzyme catalysis, (46,50,51) and considering the mild reaction conditions of the L-Cysmediated alkyne hydration, we envisaged that the organocatalytic reaction could be combined with an enzyme-mediated asymmetric reduction process to access chiral β-hydroxy sulfones, which are important building blocks in the synthesis of different APIs such as apremilast and bicalutamide. Based on our previous report on the chemoenzymatic oxosulfonylation-bioreduction process combining catalytic amounts of FeCl3 and ketoreductases (KREDs), (52) several KREDs from commercial sources and our in-house collection were selected and explored for the one-pot concurrent process, in which all reaction components are added at once.…”

Merging Organolithium Chemistry and Stereoselective Biocatalysis: Transformation of Aromatic Nitriles into Chiral Alcohols

“…However, recent innovations from our own research group and others have demonstrated that, in contrast with the aforementioned conventional wisdom, polar s ‐block organometallic RLi reagents can be used: i ) under air; ii ) in sustainable, protic, non‐toxic and non‐dried solvents [like deep eutectic solvents or even water]; and iii ) at room temperature and under air/moisture [7–14] . Consequently, this paradigm shift in organolithium chemistry illustrates the capability of RLi reagents to operate under conditions compatible with other catalysts, such as enzymes, thus opening new avenues to the design of chemoenzymatic cascades [15–24] …”

“…[7][8][9][10][11][12][13][14] Consequently, this paradigm shift in organolithium chemistry illustrates the capability of RLi reagents to operate under conditions compatible with other catalysts, such as enzymes, thus opening new avenues to the design of chemoenzymatic cascades. [15][16][17][18][19][20][21][22][23][24] The traditional challenge in transformations involving organolithium compounds and enzymes is that they typically rely on tedious multistep and energy/time consuming protocols in which intermediate isolation/ purification steps or compartmentalization of the different synthetic systems is required. [25] In some cases, these hybrid reactions RLi/enzyme have been successfully conducted sequentially in a one-pot manner.…”