Distal functionalization via transition metal catalysis

Title : Distal functionalization via transition metal catalysis

Abstract:

The ubiquitous presence of sp³ C−H bonds in natural feedstock makes them inexpensive, easily accessible, and attractive synthons for the preparation of common and/or complex molecular frameworks in biologically active natural products, pharmaceutics, agrochemicals, and materials. However, the inertness of these bonds due to the high bond dissociation energies and low polarity difference between the carbon and hydrogen atoms makes them challenging reaction partners. Moreover, the desired site-selectivity is often an issue in reactions with multiple analogous sp3 C−H bonds. To overcome these problems, transition metal-catalyzed C−H functionalization has been developed with the assistance of various well-designed directing groups which can coordinate to a metal center to deliver it on a targeted C−H bond through an appropriate spatial arrangement, enabling C−H activation via the formation of a cyclometalated species. However, the requirement of often additional steps for the construction of the directing groups and their subsequent removal after the desired operation severely hampers the efficacy and compatibility of the reactions. A promising solution would be the utilization of a transient ligand which can bind to the substrate and coordinate to the metal center in a reversible fashion. In this way, the directing group is installed, sp3 C−H functionalization occurs, and the directing group is then removed in situ without affecting the substrate function after the catalysis is finished. Overall, the whole process occurs in a single reaction pot. Herein, we are presenting our studies on transition metal-catalyzed transient directing group-enabled C−H functionalization reaction.

Audience Take Away:
This study could potentially be used for others to build small molecules in an efficient way.
This study could potentially be used for others to carry out late-stage functionalization of natural products or drug molecules.
This research could also be used by others to expand their research.

Biography:

Haibo Ge received his PhD degree in Medicinal Chemistry from The University of Kansas in 2006, and then moved to The Scripps Research Institute for postdoctoral study. In 2009, he began his independent academic career at the Indiana University – Purdue University Indianapolis and relocated to Texas Tech University in 2020. Research by his group is mainly focused on the development of novel methods for carbon–carbon and carbon–heteroatom bond formation through transition metal catalyzed C–H functionalization.