The Downey Group at the University of Richmond studies the ability of trimethylsilyl trifluoromethanesulfonate (TMSOTf) to mediate new reactivity or increase the efficiency of known reactions. The most likely downstream application of this new chemistry is in the fields of pharmaceuticals, pesticides, and herbicides. For example, the processes that we discover might be used to synthesize previously inaccessible drug candidates or streamline the production of known biologically active compounds so that drug prices can lowered or environmental waste minimized.
The ability of TMSOTf to act as both a Lewis acid and a silylating agent makes it a powerful choice in new reaction development. Because it can play two or more roles in a reaction, it can be used to develop so-called “one-pot” reactions, where two or more reactions take place in a single reaction flask without the need for purification of any intermediate compounds. This process greatly increases the efficiency of a synthetic route by shortening the time required and reducing the waste that would be generated in purification processes. Furthermore, the reaction products are often isolated as protected O-silylated products, which are useful for further synthetic steps.
Our work is currently funded by generous contributions from the Camille & Henry Dreyfus Foundation, the American Chemical Society-Petroleum Research Fund, and the University of Richmond. Previous sources of funding include the National Science Foundation, Research Corporation, and the Thomas F. and Kate Miller Jeffress Trust.
“One-pot silyl ketene acetal-formation-Mukaiyama–Mannich additions to imines mediated by trimethylsilyl trifluoromethanesulfonate” C. Wade Downey, Jared A. Ingersoll,* Hadleigh M. Glist,* Carolyn M. Dombrowski,* Adam T. Barnett* European Journal of Organic Chemistry 2015, 7287-7291.
* denotes undergraduate coauthor
“Friedel−Crafts Hydroxyalkylation of Indoles Mediatedby Trimethylsilyl Trifluoromethanesulfonate” C. Wade Downey, Christopher D. Poff,* Alissa N. Nizinski* Journal of Organic Chemistry 2015, 80, 10364-10369.
C. Wade Downey, Sarah E. Covington, Derek C. Obenschain, Evan Halliday, James T. Rague, Danielle N. Confair “Silyl trifluoromethanesulfonate-activated para-methoxybenzyl methyl ether as an alkylating agent for thiols and aryl ketones” Tetrahedron Letters 2014, 55, 5213-5215.
C. Wade Downey, Erin N. Maxwell, Danielle N. Confair “Silyl Triflate-Accelerated Additions of Catalytically Generated Zinc Acetylides to N-Phenyl Nitrones” Tetrahedron Letters 2014, 55, 4959-4961.
C. Wade Downey, Carolyn M. Dombrowski, Erin N. Maxwell, Chelsea L. Safran, Odamea A. Akomah “One-Pot Enol Silane Formation-Mukaiyama–Mannich Addition of Ketones, Amides, and Thioesters to Nitrones in the Presence of Trialkylsilyl Trifluoromethanesulfonates” European Journal of Organic Chemistry 2013, 5716-5720.
C. Wade Downey, Smaranda Craciun, Christina A. Vivelo, Ana M. Neferu, Carly J. Mueller, Stephanie Corsi “One-Pot Three-Step Thioconjugate Addition-Oxidation-Diels–Alder Reactions of Ethyl Propiolate” Tetrahedron Letters 2012, 53, 5766-5768.
C. Wade Downey, Smaranda Craciun, Ana M. Neferu, Christina A. Vivelo, Carly J. Mueller, Brian C. Southall, Stephanie Corsi, Eric W. Etchill, Ryan J. Sault “One-Pot Synthesis of (Z)-b-Sulfonyl Enoates from Ethyl Propiolate” Tetrahedron Letters 2012, 53, 5763-5765.
“Synthesis of N-Acyl-N,O-Acetals from N-Aryl Amides and Acetals in the Presence of TMSOTf” C. Wade Downey, Alan S. Fleisher,* James T. Rague,* Chelsea L. Safran,* Megan E. Venable,* Robert D. Pike Tetrahedron Letters 2011, 52, 4756-4759.
C. Wade Downey, Miles W. Johnson, Daniel H. Lawrence, Alan S. Fleisher, Kathryn J. Tracy “Acetic Acid Aldol Reactions in the Presence of Trimethylsilyl Trifluoromethanesulfonate” Journal of Organic Chemistry 2010, 75, 5351-5354.
C. Wade Downey, Brian D. Mahoney, Vincent R. Lipari "Trimethylsilyl Trifluoromethanesulfonate-Accelerated Addition of Catalytically Generated Zinc Acetylides to Aldehydes" Journal of Organic Chemistry 2009, 74, 2904-2906.
C. Wade Downey, Miles W. Johnson, Kathryn J. Tracy "One-Pot Enol Silane Formation-Mukaiyama Aldol-Type Addition to Dimethyl Acetals Mediated by TMSOTf" Journal of Organic Chemistry 2008, 73, 3299-3302.
C. Wade Downey, Miles W. Johnson "A Tandem Enol Silane Formation-Mukaiyama Aldol Reaction Mediated by TMSOTf" Tetrahedron Letters 2007, 48, 3559-3562.
Ph.D., Harvard University