Development of photocatalyzed reactions under flow conditions

Cambrigde, May 25-26, 2023 NovAliX at Flow Chemistry Europe 2023 (FCE-23) the 11th event

Guillaume Bentzinger, project manager in flow chemistry, shares recent work on development of photocatalyzed reactions under flow conditions. A work that has been done in collaboration with Laboratoire d’Innovation Moléculaire et d’Application (LIMA) from Strasbourg and the Center for Integrated Technology and Organic Synthesis (CiTOS) from Liège.

Over the last years, the good match between photo- and flow- chemistry had led to an ever-growing number of applications to the fields of drug discovery and API production.1,2 In this context, we have optimized different photochemical reactions under flow conditions to produce building blocks of interest for drug discovery program. In particular, we have: i) implemented a two-step telescoped synthesis of pyrrole relying on a photochemical Giese addition of xanthates,3 ii) transitioned a recently described protocol for Csp2-Csp3 bond formation through XAT,4 iii) optimized difluoroamidation of indoles to provide gram scale quantities and demonstrate the possibility of focused library synthesis via a two-step telescoped sequence. To support our optimization and scale-up efforts, a versatile thermoregulated photoreactor was developed using Arduino and 3D-printing technologies.

XAT cross-coupling
Difluoroamidation of indoles
Pyrroles formation

Figure 1.

This work demonstrates the potential of flow chemistry as an enabling technology in the drug discovery process. Indeed, it allows the easy  integration of photochemistry in medicinal chemistry programs through access to highly functionalized scaffolds, focused libraries and seamless scale-up.

Congratulations to the team that had contributed to these results: Guillaume Bentzinger, Guillaume Masson, Martin Cattoen, Morgan Donnard, Frédéric Leroux, Sylvain Guizzetti and Jean-Christophe Monbaliu.

Contact us to learn how our flow chemistry platform contributes to improve processes.



[1] P. Horáková, K. Kočí, Continuous-Flow Chemistry and Photochemistry for Manufacturing of Active Pharmaceutical Ingredients Molecules 27 (2022) 8536–8565. 

[2] A. Bogdan, M. Organ, Flow Chemistry as a Drug Discovery Tool: A Medicinal Chemistry Perspective Flow Chemistry for the Synthesis of Heterocycles 56 (2018) 319–341. 

[3] B. Quiclet-Sire, L. Quintero, G. Sanchez-Jimenez, S. Zard, A Practical Variation on the Paal-Knorr Pyrrole Synthesis Synlett 01 (2003) 75–78. 

[4] G. Yedase, A. Jha, V. Yatham, Visible-Light Enabled C(s p 3 )–C(s p 2 ) Cross-Electrophile Coupling via Synergistic Halogen-Atom Transfer (XAT) and Nickel Catalysis J. Org. Chem. 87 (2022) 5442– 5450.