Synthesis of Enantiopure\nFluoropiperidines via Biocatalytic\nDesymmetrization and Flow Photochemical Decarboxylative Fluorination

Low-molecular\nweight chiral amines are valuable components in medicinal\nchemistry as they serve as core templates, linking units, and substituent\nappendages. The piperidine scaffold is particularly useful among privileged\nsmall amines, with substituted variants having a great number of potential\nregio- and diastereoisomers, which allow for high stereochemical definition\nto enable a variety of productive protein interactions. Herein, we\ndescribe the successful enablement, scale-up, and delivery of >400\ng of a single isomer, (3<i>S</i>,5<i>S</i>)-1-((benzyloxy)carbonyl)-5-fluoropiperidine-3-carboxylic\nacid (>98% de and >96% ee), via 450 g-scale biocatalytic desymmetrization\nand 335 g-scale flow photochemical decarboxylative fluorination.