Efficient and scalable photochemical coupling of pinacol and aza-pinacol in continuous-flow

Photochemistry has experienced a renaissance in organic synthesis as a sustainable approach to chemical transformations. However, batch processes are often limited by the Beer–Lambert law, which reduces light penetration and scalability. Continuous-flow technology overcomes these limitations through uniform irradiation and improved control over reaction conditions. Herein, we developed highly efficient, scalable, and photocatalyst-free continuous-flow protocol for the reductive coupling of carbonyls and imines. Exploiting the intrinsic photoactivity of the substrates and utilizing N,N-diisopropylethylamine (DIPEA) as a simple sacrificial electron donor, the protocol enables the direct synthesis of vicinal 1,2-diols and 1,2-diamines, crucial structural motifs in medicinal chemistry. The continuous-flow pinacol coupling of aromatic aldehydes afforded 1,2-diols in excellent yields (up to 98%) within a residence time of just 10 minutes, demonstrating a ~ 6.9-fold increase in productivity compared to batch conditions. Similarly, the imino-pinacol coupling provided 1,2-diamines in high yields in 30 minutes without the need for strict deaeration. Further investigations successfully integrated both the imine condensation and the photochemical coupling into a single, fully continuous setup, yielding the target diamine in an 80% yield. Continuous-flow technologies offer advantages over batch processes in photochemical organic synthesis by ensuring uniform irradiation, enhanced mass transfer, and precise control over reaction parameters. Here, the authors develop an efficient and scalable continuous-flow protocol for the photochemical coupling of pinacol and aza-pinacol.