Dean Toste

Organic, Organometallic Chemistry — Organic and organometallic chemistry are employed in the development of new synthetic methods, enantioselective catalysts and strategies for the synthesis of natural products.

Research in my group is primarily aimed toward the development of catalysts and catalytic reactions and methods for organic synthesis. Ultimately, we are interested in using these methods to address problems in the synthesis of complex molecules possessing interesting structural, biological and physical properties. As such, our research program spans the areas of organic synthesis, catalysis, and organometallic chemistry. Two mechanistically distinct applications of complexes with metal-ligand multiple bonds are illustrative of our approach. First, we envision a new approach to catalysis utilizing transition metal-ligand pi-bonds to activate sigma-bonds towards addition reactions. We are also examining metal-ligand and ancillary ligand combinations with the ultimate goal of developing enantioselective versions of these reactions. The concept of employing complexes containing metal-ligand multiple bonds as bifunctional catalysts for sigma-bond activation represents a dramatic shift from the traditional applications of metal-oxo complexes as catalysts for atom transfer (epoxidations, aziridinations and dihydroxylation) and for functional group oxidations. Second, we are developing metal-dioxo complexes as catalysts for three-component cycloadditions in which the oxo ligand is one of the partners. We are applying these cycloaddition reactions to the synthesis of natural products such as kallolide A (anti-inflammatory and cytotoxic properties).

A second area of research is the development of new catalysts and synthetic methods for the formation of carbon-carbon and carbon-heteroatom bonds. Of particular interest are addition reactions including additions to olefins and alkynes, alkene-alkene coupling and other atom transfer additions. For example, we are investigating catalytic methods for the addition of water and alcohols to enones as an alternative entry into aldol adducts. Our ultimate goal is to develop enantioselective variants of these reactions and utilize them in the synthesis of natural products such as epoxyquinol (antiangiogenic activity), the eudesmanolides (antitumor) and the amphidinolides (cytotoxic).