Oxazolidinone-Derived N-Centered Radicals: in Batch and in Flow Photoredox Catalysis

The recent advancements in radical chemistry have paved the way for new opportunities in synthesis, solving challenges that more conventional methodologies have historically encountered. Traditional approaches used to build C-N bonds often rely on high temperatures and pre-functionalized coupling partners, such as Cu-catalyzed Ullman type coupling or Pd-catalyzed Buchwald-Hartwig amination.1 However, in the last few years, some of these issues have been solved by the use of N-centered radicals generated by photoredox catalysis. These radicals have proven effective for building C-N bonds under mild reaction conditions. The use of N-centered radicals, when combined with flow chemistry, have proven to be effective also for large-scale productions, overcoming issues related to limited light penetration associated to batch processes. 2 In this context, we focused our attention on the development of novel synthetic methodologies for the synthesis of products of pharmaceutical interest such as Linezolid and Eperezolid3 (Figure 1a), involving the use of N-oxazolidinone radicals generated by photocatalytic approach. An easy protocol for the generation of N-oxazolidinone radicals have been developed (Figure 1b), which were successfully employed in amidation reactions of various aromatic substrates performed under traditional batch and continuous flow conditions. These initial investigations mark a significant step toward devising efficient and sustainable methods for the synthesis of APIs.