Chiral α-(hetero)aryl primary amines are gaining momentum for their biological activities and their use as building blocks in more complex molecules. Here we report a continuous chemoenzymatic strategy from 2-acetyl-6-bromopyridineenabled by careful solvent selection and phase switching. Combining a first biocatalytic transamination reaction performed by TsRTA in a biphasic system in continuous flow, with in line Boc-protection and Suzuki coupling of a (substituted)phenylboronic acid, achieving conversions up to >99% towards tert-butyl (R)-(1-(6-(substituted) phenylpyridin-2-yl)ethyl)carbamate as the final product. This strategy not only constitutes an important example of chemoenzymatic combinations in continuous flow but highlights the importance of the reaction design to minimize waste (through unreacted substrate recirculation), avoid time intensive workups (through inline extractions) and achieve the productin a space time yield of 68 mg·L^-1·h^-1 with excellent enantiomeric excess (99% ee).

Great collaboration with Novartis!