“Enantioselective and Remote C–H Activation Reactions”

Seminar series
Organic Colloquium
Thu, May 11 5:00pm
CS24 Young Hall
Speaker Professor Jin-Quan Yu
The Scripps Research Institute
Department of Chemistry

Organic Colloquium

“Enantioselective and Remote C–H Activation Reactions”

Abstract.  The past decade has witnessed a renaissance in metal-catalyzed C–H activation reactions. The vast majority of these reactions proceed via cyclometallation, in which a strongly coordinating functional group binds to the metal and facilitates cleavage of a proximate C–H bond. These substrates driven reactions become problematic background reactions for developing enantioselective C–H activation reactions. The use of weak coordination from substrates to direct metal insertion opens up possibility of designing ligand to significantly influence C–H activation reactions. In ideal scenario of developing asymmetric C–H activation reactions, the reaction should only proceed when chiral ligands are present. We have recently discovered a number of ligand scaffolds that can enable C–H activation reactions of weakly coordinating substrates that are otherwise unreactive. Further development of chiral ligands have enabled the enantioselective C–H activation reactions of methylene C–H bonds for the first time (Scheme 1). This effort has also led to the development of a biomimetic asymmetric transformation based on desymmetrization of an ubiquitous isopropyl group.

Inspired by how enzymes use directing effect to achieve remote selective C–H activation, we have developed a number of site-selective remote C–H activation reactions which are fundamentally distinct from the classic directed C–H activation via cyclometalation processes. We focused our design on recognition of distance and geometry as the simplest parameters to achieve site selectivity, which has allowed us to activate C–H bonds at remote sites that are previously not accessible. The combination of remote directing effect and ligand acceleration is analogous to flying a kite in the wind.