Harvesting the fragment-based nature of bifunctional organocatalysts to enhance their activity

Bifunctional hydrogen-bond donors/amines are commonly encountered organocatalysts in asymmetric synthesis. Existing computational tools do not take full advantage of their modularity to suggest tailored designs because they generally rely on evaluating the organocatalyst's structure as a whole. Herein, we introduce a fragment-based approach, coupled with volcano plots and activity maps, to evaluate hundreds of building block combinations and extract mechanistic insight. This bottom-up protocol gives feedback on the choice of improved molecular fragments and makes activity-based screening faster and more transferable.

Automated summary

In this study, a fragment-based approach is introduced to evaluate the combinations of building blocks and extract mechanistic insight in the design of bifunctional hydrogen-bond donors/amines as organocatalysts. The use of volcano plots and activity maps allows for faster and more transferable activity-based screening.