González-Esguevillas María, Fernández David F, Rincón Juan A, Barberis Mario, de Frutos Oscar, Mateos Carlos, García-Cerrada Susana, Agejas Javier, MacMillan David W C
Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, United States.
Centro de Investigación Eli Lilly, S. A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain.
ACS Cent Sci. 2021 Jul 28;7(7):1126-1134. doi: 10.1021/acscentsci.1c00303. Epub 2021 Jun 8.
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.
光氧化还原催化已成为合成复杂分子的强大且通用的平台。虽然光催化已在制药行业的小规模间歇化学中广泛应用，但由于间歇光催化在放大过程中存在固有挑战，最近的努力集中在过程化学中进行这些转化。然而，将优化的间歇条件转化为流动装置具有挑战性，一种快速、方便且廉价的通用方法在很大程度上仍然难以捉摸。在此，我们报告了一种新方法的开发，该方法使用微尺度高通量实验（HTE）平台来确定可直接转化为流动系统的最佳反应条件。一个关键设计点是在微尺度反应板内模拟流动-容器路径，这使得仅通过少量同步实验就能快速确定最佳流动反应条件。该方法已针对一系列广泛使用的光氧化还原反应进行了验证，重要的是，发现它能准确地转化为几种商业流动反应器。我们预计这种新的光催化HTE方法的通用性和操作效率将允许快速确定大量用于放大的流动方案。
