Development of a Continuous Flow Baldwin Rearrangement Process and Its Comparison to Traditional Batch Mode

A new and highly efficient continuous flow process is presented for the synthesis of aziridines via the thermal Baldwin rearrangement. The process was initially explored using traditional batch synthesis techniques but suffered from moderate yields, long reaction times, and moderate diastereoselectivities. Here we demonstrate that the process can be greatly improved upon its transfer to continuous flow, which afforded the aziridine targets in high yields, short reaction times, and consistently high diastereoselectivities, with the high-throughput process rendering multigram quantities of product in short periods of time. In addition, flow processing extended the substrate scope including several examples that had failed in batch mode, thus demonstrating the value of this overlooked entry into valuable aziridine species.