TITLE: CLP Seminar: Jon Ellman, Eugene Higgins Professor of Chemistry and Professor of Pharmacology, Yale University
WHEN: April 29, 3:00 PM – 4:00 PM
Meeting ID: 989 6533 2074
New C–H functionalization reactions for the rapid preparation of pharmaceuticals and natural products
Versatile and highly functional group compatible Rh- and Co-catalyzed annulations will be described for the rapid assembly of drug relevant nitrogen heterocycles from simple and readily available inputs. Reactions will be presented that proceed through imidoyl C–H activation to provide many different classes of nitrogen heterocycles by annulations with a variety of different coupling partners. These types of reactions are particularly useful not only due to their high functional group compatibility but also because the imine starting materials can be generated in situ from vast numbers of aldehydes and amines. The first examples of three-component sequential C−H bond additions to two different coupling partners will also be reported. This approach will be described for multiple types of coupling partners and for transformations that proceed with high regioselectivity and stereoselectivity. Catalytic cycles will be proposed that are supported by structural characterization of metallacycle intermediates, regio- and stereochemical outcomes of reactions, and the use of isotopically labeled substrates. The utility of the disclosed methods will be illustrated by short and efficient syntheses of natural products and pharmaceutical agents.
The ability to rapidly and efficiently synthesize new chemical matter provides unlimited opportunities to discover and develop compounds with incredibly diverse properties and applications ranging from precise tools to study biological phenomena, to pharmaceutical agents to treat unmet medical conditions, to new methods of energy storage and production.
One way that the Ellman laboratory seeks to contribute to the incredible opportunities provided by chemical synthesis is through the design and development of efficient and general methods for achieving essential bond connections. For example, the Ellman laboratory has pioneered the development of tert-butanesulfinamide chemistry, which has rapidly become one of the most extensively used approaches for the asymmetric synthesis of amine-containing compounds, a class of structures that is especially prevalent in pharmaceutical agents. Another area of focus is the catalytic conversion of C-H to C-C bonds enabling the direct preparation of an incredibly diverse array of complex structures from simple precursors.
The Ellman laboratory also is engaged in the design and synthesis of structures that interact with biological systems. For example, tools continue to be developed to rapidly establish enzyme substrate specificity to provide a window into understanding enzyme function. Moreover, compounds are designed and developed to potently and selectively interact with specific biomolecular targets to define their biological role, establish relevance for the treatment of disease, and provide key starting points for drug development.