Research Interests | PublicationsCollaborations

Reaction Discovery

Access to compounds with interesting and useful properties relies upon the discovery and development of new synthetic transformations. To this end, the Brummond group has exploited allenes in thermal and transition-metal catalyzed reactions to obtain novel arrays of atoms. The scheme on the right depicts a few of the carbocyclization and cyclocarbonylation reactions discovered in our group. We are currently investigating these and other reactions for their scope and synthetic utility.

Natural Products and Biologically Relevant Compounds

Synthetic methods developed in the Brummond research program afford functionally dense compounds important to the drug discovery process. Natural products prepared in our group include anticancer agents hydroxymethylacylfulvene, 15-deoxy-Δ 12,14 PGJ2 and immunosuppressant FR901483. We are currently using an allenic Pauson-Khand reaction to prepare 6,12-guaianolides of which thapsigargin and arglabin are two biologically relevant representatives of this very important and class of sesquiterpene lactones.

Diversity Oriented Synthesis and Expansion of Chemical Space

The Brummond group has developed a DOS strategy, whereby structurally unique compounds are obtained by reacting a single compound to different reaction conditions. The power of this reagent-based approach to skeletal diversification has subsequently been demonstrated by the preparation of multiple libraries of compounds that occupy unique chemical space and have interesting biological activity. These compounds currently reside in the NIH Molecular Repository and their structures and bioactivity can be accessed using Pubchem.

Reaction Mechanisms
Mechanistic insight gained through both experiment and theory accelerates the scope and limitation studies of new transformations discovered in our laboratory. For example, collaborations with computational chemists who use high-level DFT theory have led to an explanation for the selective reactivity of the distal and proximal double bonds of the allene when using rhodium and molybdenum catalysis. The figure on the right depicts an energy diagram for a thermal [2 + 2] cycloaddition reaction that is computationally predicted to occur by way of a biradical intermediate. This hypothesis is further supported by radical probe experiments                     
Molecular Sensors

A rare intramolecular dehydrogenative dehydro-Diels–Alder reaction was observed in the Brummond group, affording high yields of cyclopenta[b]naphthalenes. Synthesis of functionalized naphthalenes remains a synthetic challenge, moreover, methods to access this very important class of aromatic compounds have not kept up with the demand for new structure and function requirements. This utility of this naphthalene synthesis has been demonstrated by its application to the synthesis of a series of naphthalene-containing solvatochromic fluorophores that are structurally related to Prodan, a compound that is currently the state of the art for environmental sensing. The graphic on the right depicts one of our fluorophores in four solvents differing in polarity. All fluorophore emission maxima, and nearly all absorption maxima were significantly red-shifted when compared to Prodan with several showing red-shifts well into the visible region. Shifting absorption and emission maxima of a fluorophore into the visible region increases its utility in biological applications.