Enantioselective C-H Activation with Bifunctional Ligands: From Curiosity to Industrialization

 

Enantioselective C-H Activation with Bifunctional Ligands: From Curiosity to Industrialization

 

Date: 12^th June, 2025 (Thursday)

Time: 5:30 - 6:30 pm (HKT)

 

Venue: Lecture Theatre P1, Chong Yuet Ming Chemistry Building

 

The Scripps Research Institute

 

The widespread presence of C–H bonds at various sites of synthetic substrates renders C–H activation the most powerful platform for developing catalytic reactions for synthesis. Among numerous challenges, achieving enantioselective C-H activation via asymmetric metalation stands out as a holy grail in chemistry. Despite century-long efforts, seeking solutions to this problem has met with limited success due to a fundamental challenge: lack of ligands that can accelerate C–H activation reactions.

 

By combining the weak coordination (entropy) from substrates and ligand acceleration (enthalpy), we have realized enantioselective C-H activation using all major approaches in classic asymmetric catalysis including desymmetrization, kinetic resolution, dynamic kinetic resolution, and enantioselection. Most notably, eight generations of bi-functional ligands (MPAA, APAQ, APAO, MPAAm, MPAThio, Pyridine-Pyridone, Amine-Pyridone, Amide-Pyridone) have been developed to enable a wide range of enantioselective^1-6 and site-selective^7-15 C–H activation reactions of diverse classes of native substrates for the construction of point, axial and planar chirality. In parallel, we have realized C–H hydroxylation using molecular oxygen or aqueous hydrogen peroxide as the terminal oxidants, paving the way for large-scale industrialization.^11,12 Applications of our new catalysts and reactions at BMS, Lilly, Merck and Vertex will be highlighted.

 

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