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.