Industrial and Academic Applications of High Throughput Experimentation in Reaction Optimization

Abstract: Over the past decade, high throughput experimentation (HTE) has gained recognition as a valuable reaction optimization tool, especially in the field of catalysis. Thus, the technology has been adopted by an increasing number of industrial and academic research groups. The first half of this talk will focus on an industrial application of HTE in the development of an enantioselective synthesis of α-methyl-β-cyclopropyldihydrocinnamates for a drug discovery program. We leveraged the technology to define scalable Suzuki-Miyaura cross-coupling conditions affording (Z)-α-methyl-β-cyclopropylcinnamates and subsequent ruthenium-catalyzed asymmetric hydrogenation conditions yielding the desired products in high enantio- and diastereoselectivities. The second half of the lecture will focus on an academic application of HTE in the optimization of α-hydroxy C–H bond arylations via triple metallophotoredox hydrogen atom transfer (HAT) catalysis. In the described academic collaboration, we leveraged high throughput catalyst loading studies to gain a deeper understanding of byproduct formation pathways. We subsequently used the technology to define additive and base combinations that minimized byproduct formation, significantly improving desired product yields. These examples highlight the utility of HTE in both industrial and academic settings.