Scalable Photoinduced Cycloaddition for the Synthesis of Biorelevant Oxazoles

The
practical and scalable synthesis of bioactive oxazoles remains
challenging due to the limitations of existing methods, which often
rely on intramolecular cyclization, transition metal catalysis, or
harsh reaction conditions. To overcome these issues, we have developed
a photoflow-mediated [3 + 2] cycloaddition between diazo compounds
and nitriles, enabling a streamlined and step-efficient approach to
oxazole synthesis. This strategy has facilitated the scalable preparation
of various oxazole-based alkaloids, including balsoxine, texamine,
uguenenazole, pimprinine, and pimprinaphine, as well as drug precursors
and deuterium-labeled oxazoles. By introducing a modular, benchtop
flow process, our method significantly improves the scalability and
accessibility of diverse bioactive oxazoles.