Associate Professor of Chemistry
Ph.D. Harvard University, 2001
(Organic and Organometallic Chemistry)
The Michael group is interested in developing new methodologies for organic synthesis. Synthetic organic chemistry is a powerful tool for creating complex molecules for use in materials science, pharmaceuticals, and molecular biology. Our goal is to identify difficult transformations in synthetic organic chemistry and to design new methods to efficiently accomplish those transformations. Such an approach requires expertise in organic synthesis, physical organic chemistry, and organometallic chemistry. Mechanistic studies will be an important part of these investigations since understanding the specific details of useful transformations will aid in the design of more advanced methods. Additionally, the design of efficient syntheses of interesting organic molecules will provide an important illustration of the usefulness and power of these newly developed methods. Specific examples of the types of reactions we are interested in are introduced below.
Amination of Unsaturated Hydrocarbons
The vast majority of biologically active compounds contain nitrogen. Therefore, general methods for the direct, efficient incorporation of nitrogen-containing functional groups are particularly important. The Michael group has recently disclosed a highly effective catalyst for the direct addition of N-H bonds to unactivated alkenes (hydroamination). This catalyst can be used for the selective construction of medicinally important heterocycles. Further research in this area is directed towards other methods for amination and diamination of carbon-carbon double and triple bonds, as well as the selective introduction of more complex nitrogen-containing functional groups, such as nitroso and nitro groups.
The potential toxicity of metal-based catalysts and reagents in organic chemistry is a significant drawback when using these compounds for the synthesis of biologically active molecules, especially pharmaceuticals. In this context, the Michael group is also interested in expanding the types of reactivity that can be catalyzed by purely organic compounds, particularly Brønsted acid catalysis and oxidation/reduction chemistry.
One of the biggest challenges in developing new methods for organic synthesis is controlling the relative and absolute stereochemistry of the products. Studying and optimizing the factors that influence the regioselectivity, diastereoselectivity, and enantioselectivity of any new catalytic process is a primary goal of this research.
Teh, W. P.; Michael, F. E. “Palladium-Catalyzed Cross-Coupling of N-Sulfonylaziridines and Alkenylboronic Acids: Stereospecific Synthesis of Homoallylic Amines with Di-and Trisubstituted Alkenes.” Org. Lett. 2017, 19, 1738-1740.
Duda, M. L.; Michael, F. E. “Palladium-Catalyzed Cross-Coupling of N-Sulfonylaziridines with Boronic Acids.” J. Am. Chem. Soc. 2013, 135, 18347-18349.
Pierson, J.; Ingalls, E. L.; Vo, R.; Michael, F. E. “Palladium(II)-catalyzed Intramolecular Hydroamination of 1,3-Dienes to Give Homoallylic Amines.” Angew. Chem., Int. Ed. 2013, 52, 13311-13313.
Ingalls, E. L.; Sibbald, P. A.; Kaminsky, W.; Michael, F. E. “Enantioselective Palladium-Catalyzed Diamination of Alkenes Using N-Fluorobenzenesulfonimide.” J. Am. Chem. Soc. 2013, 135, 8854-8856.
Siegel, J. B.; Zanghellini, A.; Lovick, H. M.; Kiss, G.; Lambert, A. R.; St.Clair, J. L.; Gallaher, J. L.; Hilvert, D.; Gelb, M. H.; Stoddard, B.; Houk, K. N.; Michael, F. E.; Baker, D. “Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction.” Science 2010, 329, 309-313.
Lovick, H. M.; Michael, F. E. “Metal-Free Highly Regioselective Aminotrifluoroacetoxylation of Alkenes.” J. Am. Chem. Soc. 2010, 132, 1249-1251.
Sibbald, P. A.; Rosewall, C. F.; Swartz, R. D.; Michael, F. E. “Mechanism of N-Fluorobenzenesulfonimide Promoted Diamination and Carboamination Reactions: Divergent Reactivity of a Pd(IV) Species.” J. Am. Chem. Soc. 2009, 131, 15945-15951.