TY - JOUR
T1 - Rapid Optimization of Photoredox Reactions for Continuous-Flow Systems Using Microscale Batch Technology
AU - González-Esguevillas, María
AU - Fernández, David F.
AU - Rincón, Juan A.
AU - Barberis, Mario
AU - De Frutos, Oscar
AU - Mateos, Carlos
AU - García-Cerrada, Susana
AU - Agejas, Javier
AU - Macmillan, David W.C.
N1 - Funding Information:
Research reported in this publication was supported by the NIH National Institute of General Medical Sciences (R35GM134897-01) and the Princeton Catalysis Initiative (PCI). This work was supported by Eli Lilly and Company through the Lilly Research Award Program (LRAP) as well as kind gifts from Merck, Janssen, BMS, Genentech, Celgene, and Pfizer. D.F.F. thanks Xunta de Galicia for a postdoctoral fellowship (ED481B-2019-005).
Publisher Copyright:
©
PY - 2021/7/28
Y1 - 2021/7/28
N2 - Photoredox catalysis has emerged as a powerful and versatile platform for the synthesis of complex molecules. While photocatalysis is already broadly used in small-scale batch chemistry across the pharmaceutical sector, recent efforts have focused on performing these transformations in process chemistry due to the inherent challenges of batch photocatalysis on scale. However, translating optimized batch conditions to flow setups is challenging, and a general approach that is rapid, convenient, and inexpensive remains largely elusive. Herein, we report the development of a new approach that uses a microscale high-throughput experimentation (HTE) platform to identify optimal reaction conditions that can be directly translated to flow systems. A key design point is to simulate the flow-vessel pathway within a microscale reaction plate, which enables the rapid identification of optimal flow reaction conditions using only a small number of simultaneous experiments. This approach has been validated against a range of widely used photoredox reactions and, importantly, was found to translate accurately to several commercial flow reactors. We expect that the generality and operational efficiency of this new HTE approach to photocatalysis will allow rapid identification of numerous flow protocols for scale.
AB - Photoredox catalysis has emerged as a powerful and versatile platform for the synthesis of complex molecules. While photocatalysis is already broadly used in small-scale batch chemistry across the pharmaceutical sector, recent efforts have focused on performing these transformations in process chemistry due to the inherent challenges of batch photocatalysis on scale. However, translating optimized batch conditions to flow setups is challenging, and a general approach that is rapid, convenient, and inexpensive remains largely elusive. Herein, we report the development of a new approach that uses a microscale high-throughput experimentation (HTE) platform to identify optimal reaction conditions that can be directly translated to flow systems. A key design point is to simulate the flow-vessel pathway within a microscale reaction plate, which enables the rapid identification of optimal flow reaction conditions using only a small number of simultaneous experiments. This approach has been validated against a range of widely used photoredox reactions and, importantly, was found to translate accurately to several commercial flow reactors. We expect that the generality and operational efficiency of this new HTE approach to photocatalysis will allow rapid identification of numerous flow protocols for scale.
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U2 - 10.1021/acscentsci.1c00303
DO - 10.1021/acscentsci.1c00303
M3 - Article
C2 - 34345665
AN - SCOPUS:85109038370
SN - 2374-7943
VL - 7
SP - 1126
EP - 1134
JO - ACS Central Science
JF - ACS Central Science
IS - 7
ER -