One‐Pot Synthesis of Chiral N‐Arylamines by Combining Biocatalytic Aminations with Buchwald–Hartwig N‐Arylation

The combination of biocatalysis and chemo‐catalysis increasingly offers chemists access to more diverse chemical architectures. Here, we describe the combination of a toolbox of chiral‐amine‐producing biocatalysts with a Buchwald–Hartwig cross‐coupling reaction, affording a variety of α‐chiral aniline derivatives. The use of a surfactant allowed reactions to be performed sequentially in the same flask, preventing the palladium catalyst from being inhibited by the high concentrations of ammonia, salts, or buffers present in the aqueous media in most cases. The methodology was further extended by combining with a dual‐enzyme biocatalytic hydrogen‐borrowing cascade in one pot to allow for the conversion of a racemic alcohol to a chiral aniline. A two‐step, one‐pot chemoenzymatic synthesis of chiral anilines is reported. Chiral‐amine‐producing biocatalysts have been combined in the same pot as a Pd catalyst to allow the direct conversion of prochiral and racemic starting materials to enantiopure anilines. The use of a surfactant to enable this one‐pot process is a first for biocatalysis.