Asymmetric organocatalysis in drug discovery and development for active pharmaceutical ingredients

Over the last 20 years, it has become clear that organocatalysis is the third pillar of catalysis. The low reactivity in the early days of organocatalysis has been overcome with the invention of more efficient catalysts, and by harnessing enabling technologies like continuous-flow chemistry and photo-redox catalysis.The main focus of this review is on the development over the last 10-15 years of key APIs using asymmetric organocatalysis. Due to significant engineering advances, and also due to the need for continuous manufacturing, flow and photo-redox approaches are becoming more widespread.Over the last 20 years, organocatalysis has been used on various occasions for accessing chiral drugs. The great advantage of using these catalysts is that the final active pharmaceutical ingredient (API) is metal-free. Also due to their inherent stability in air and water, they are very amenable to recovery via attachment to appropriate solid supports and also application in continuous flow systems. In recent years, more efficient organocatalysts have been developed, which includes the photoredox types, with much potential for chiral API synthesis.