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20 Photocatalysis in the Pharmaceutical Industry

DOI: 10.1055/sos-SD-229-00341

DiRocco, D. A.; Schultz, D. M.Science of Synthesis: Photocatalysis in Organic Synthesis, (20181611.

General Introduction

Since the initial reports of photoredox catalysis, the pharmaceutical industry has been interested in applying these nontraditional bond-forming reactions to access and derivatize biologically active molecules.[‌1‌,‌2‌] While new photoredox methods are continuously being published, ones that exhibit broad tolerance toward polar functional groups and utilize “off the shelf” coupling partners are considered ideal for pharmaceutical development. In an effort to accommodate these desires, industrial–academic collaborations have become an avenue to make photoredox catalysis more accessible to industrial researchers. Specifically, medicinal chemists have benefited from photochemical late-stage functionalization methods that provide direct access to unique analogues from a single advanced pharmaceutical intermediate. In turn, scaling up photochemical transformations through flow platforms[‌3‌] and the development of sustainable photocatalysts have greatly enabled process chemists.[‌4‌]

Industrial and industrial–academic collaborations have also played a significant role in bringing forward new technologies for advancing photocatalysis. For instance, the development of a 96-well LED array for high-throughput experimentation (HTE) has allowed for rapid screening of photoredox conditions.[‌5‌] In turn, the desire to improve and standardize the way that photochemical reactions are run has resulted in the development of a photon-efficient photoreactor that can reduce reaction times by at least 50%.[‌6‌] More recently, a straightforward means of determining quantum yield of both UV- and visible-light-mediated processes has been achieved through the use of LED NMR spectroscopy and readily available actinometers.[‌7‌]

In the following sections of this chapter, industrial applications of photoredox catalysis are discussed that have not only impacted pharmaceutical development but have furthered the field. The results of such work have resulted in a broad range of useful reactions, including oxidations, methylations, arylations, and fluorinations, that have been successfully applied to complicated heterocycles but also biomolecules exceeding 2 kDa. Moreover, through the use of flow, several photoredox reactions have been demonstrated on scale, highlighting the potential of these methodologies to impact not only drug discovery but also drug manufacturing.