posted on 2021-06-08, 16:04authored byMaría González-Esguevillas, David F. Fernández, Juan A. Rincón, Mario Barberis, Oscar de Frutos, Carlos Mateos, Susana García-Cerrada, Javier Agejas, David W. C. MacMillan
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.