An Enlightening Reactor

I n recent years, the reaction vessel by which chemists perform organic reactions has undergone major changes. No longer limited to round-bottom flasks, we can perform experiments in microwave ovens, flow reactors, and 96-well plates. Each of these technologies has enabled breakthroughs in organic synthesis not easily achieved using conventional flasks. In the rapid development of photoredox technology, a gap in physical technology has led to a wide range of protocols that use different light sources. A standard, affordable reactor that is easy to use would accelerate the use of photoredox methodology. To address this, a collaboration between Merck researchers and the MacMillan laboratory at Princeton has produced an integrated photoreactor built with a modular design (Figure 1). The simple and elegant design allows for efficient catalysis of photoredox reactions. A sampling of top pharmaceutical photoredox coupling reactions were tested with the new integrated photoreactor. In general, the small-scale photoreactor could be employed broadly. The new photoreactor enables rate accelerations between 2 to 20 times when evaluating various photoredox transformations using a 360° light source. The designer photoreactor could also precisely control the LED output power, a parameter previously challenging to control. The silyl-mediated cross-electrophilic cross-coupling reaction was sensitive to the buildup of hydrobromic acid at the maximum LED output level (Figure 2). However, by precisely controlling the power level, the scientists could balance reaction rates, which resulted in a 6-fold improvement in reaction time. In the future, the development of a photoreactor that can hold multiple reaction vials will enable accelerated discoveries for new technologies in fragmentbased coupling reactions. Most importantly, these integrated photoreactors were implemented across 10 different medicinal chemistry groups at 4 different Merck research sites. This led to the successful standardization of LED protocols used across the sites. Synergistic partnerships between academia and industry