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, Organic Syntheses, Inc., and the Thomas F. and Kate Miller Jeffress Trust.
University of Richmond undergraduate coauthors are denoted with an asterisk (*).
17. “One-pot enol silane formation-Mukaiyama aldol reactions: crossed aldehyde-aldehyde coupling, thioester substrates, and reactions in ester solvents” C. Wade Downey, Grant J. Dixon,* Jared A. Ingersoll,* Claire N. Fuller,* Kenneth W. MacCormac,* Anna Takashima,* Rohina Sediqui* Tetrahedron Letters 2019, 60, 151192. link
16. “One-Pot Enol Silane Formation-Alkylation of Ketones with Propargyl Carboxylates Promoted by Trimethylsilyl Trifluoromethanesulfonate” C. Wade Downey, Danielle N. Confair,* Yiqi Liu,* Elizabeth D. Heafner* Journal of Organic Chemistry 2018, 80, 12931-12938. link
15. “Chalcone and cinnamate synthesis via one-pot enol silane formation-Mukaiyama aldol reactions of ketones and acetate esters” C. Wade Downey, Hadleigh M. Glist,* Anna Takashima,* Samuel R. Bottum,* Grant J. Dixon* Tetrahedron Letters 2018, 59, 3080-3083. link
14. “Mukaiyama addition of (trimethylsilyl)acetonitrile to dimethyl acetals mediated by trimethylsilyl trifluoromethanesulfonate” C. Wade Downey, Alice Y.-K. Lee,* John R. Goodin,* Courtney J. Botelho,* William M. Stith* Tetrahedron Letters 2017, 58, 3496-3499. link
13. “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. link
12. “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. link
11. “Silyl trifluoromethanesulfonate-activated para-methoxybenzyl methyl ether as an alkylating agent for thiols and aryl ketones” C. Wade Downey, Sarah E. Covington,* Derek C. Obenschain,* Evan Halliday,* James T. Rague,* Danielle N. Confair* Tetrahedron Letters 2014, 55, 5213-5215. link
10. “Silyl Triflate-Accelerated Additions of Catalytically Generated Zinc Acetylides to N-Phenyl Nitrones” C. Wade Downey, Erin N. Maxwell,* Danielle N. Confair* Tetrahedron Letters 2014, 55, 4959-4961. link
9. “One-Pot Enol Silane Formation-Mukaiyama–Mannich Addition of Ketones, Amides, and Thioesters to Nitrones in the Presence of Trialkylsilyl Trifluoromethanesulfonates” C. Wade Downey, Carolyn M. Dombrowski,* Erin N. Maxwell,* Chelsea L. Safran,* Odamea A. Akomah* European Journal of Organic Chemistry 2013, 5716-5720. link
8. “Diethyl Ethoxymethylenemalonate” Lutz F. Tietze, Holger Geissler, C. Wade Downey. In Encyclopedia of Reagents in Organic Synthesis [Online] 2013, Tomislav Rovis, Ed.; Wiley & Sons: New York.
7. “One-Pot Three-Step Thioconjugate Addition-Oxidation-Diels–Alder Reactions of Ethyl Propiolate” C. Wade Downey, Smaranda Craciun,* Christina A. Vivelo,* Ana M. Neferu,* Carly J. Mueller,* Stephanie Corsi* Tetrahedron Letters 2012, 53, 5766-5768. link
6. “One-Pot Synthesis of (Z)--Sulfonyl Enoates from Ethyl Propiolate” 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* Tetrahedron Letters 2012, 53, 5763-5765. link
5. “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. link
4. “Acetic Acid Aldol Reactions in the Presence of Trimethylsilyl Trifluoromethanesulfonate” C. Wade Downey, Miles W. Johnson,* Daniel H. Lawrence,* Alan S. Fleisher,* Kathryn J. Tracy* Journal of Organic Chemistry 2010, 75, 5351-5354. link
3. “Trimethylsilyl Trifluoromethanesulfonate-Accelerated Addition of Catalytically Generated Zinc Acetylides to Aldehydes” C. Wade Downey, Brian D. Mahoney,* Vincent R. Lipari* Journal of Organic Chemistry 2009, 74, 2904-2906. link
2. “One-Pot Enol Silane Formation-Mukaiyama Aldol-Type Addition to Dimethyl Acetals Mediated by TMSOTf” C. Wade Downey, Miles W. Johnson,* Kathryn J. Tracy* Journal of Organic Chemistry 2008, 73, 3299-3302. link
1. “A Tandem Enol Silane Formation-Mukaiyama Aldol Reaction Mediated by TMSOTf” C. Wade Downey, Miles W. Johnson* Tetrahedron Letters 2007, 48, 3559-3562. link