Chemoenzymatic One‐Pot Cascade for the Construction of Asymmetric C−C and C−P Bonds via Formal C−H Activation

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AbstractThe integration of organocatalysis and enzyme catalysis in one‐pot cascade processes allows for the efficient construction of complex molecular architectures with high levels of stereocontrol. However, challenges related to reaction compatibility between both processes are often a limitation for the development of efficient synthetic routes. In this study, we describe the combination of an enzymatic aerobic oxidation followed by the squaramide‐mediated asymmetric formation of C−P and C−C bonds to access important building blocks such as chiral α‐hydroxyphosphonates and β‐nitro alcohols in good yields and enantiomeric ratios. This sequential process is conducted in a one‐pot fashion within a biphasic system and represents a pioneering example of a chemoenzymatic cascade involving aerobic biooxidation and an organocatalytic step operating under hydrogen‐bond activation mode and under mild reaction conditions.