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.<\/p>\n
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.<\/p>\n
FUNDING<\/strong> PUBLICATIONS<\/strong> 23. Tyler G. Chong,* Alex V. Helbling,* Remi D. Graff,* C. Wade Downey. One-pot silyl imidate formation-N-alkylation reactions of amides with propargyl propionates. Tetrahedron Letters<\/em> 2023<\/strong>, 128<\/em>, Article 154718. link<\/a><\/p>\n 22. Elizabeth D. Heafner,* Xuechun Lin,* Alexa H. Connors,* Hanyu Zhong,* R. Joseph Coyle,* Yiqi Liu,* C. Wade Downey. One-pot enol silane formation-allylation of ketones promoted by trimethylsilyl trifluoromethanesulfonate. Synthesis<\/em> 2023<\/strong>, 55<\/em>, 2377-2389. link<\/a><\/p>\n 21. Grant J. Dixon,* Michael R. Rodriguez,* Tyler G. Chong,* Kevin Y. Kim,* C. Wade Downey. Synthesis of beta,beta-Disubstituted Styrenes via Trimethylsilyl Trifluoromethanesulfonate-Promoted Aldehyde-Aldehyde Aldol Addition-Deformylative Elimination. The Journal of Organic Chemistry<\/em> 2022<\/strong>, 87<\/em>, 14846-14854. link<\/a><\/p>\n 20. Zachary Z. Oracheff,* Helen L. Xia,* Christopher D. Poff,* Scott E. Isaacson,* C. Wade Downey. Friedel\u2013Crafts addition of indoles to nitrones promoted by trimethylsilyl trifluoromethanesulfonate. The Journal of Organic Chemistry<\/em> 2021<\/strong>, 86<\/em>, 17328-17336. link<\/a><\/p>\n 19. Danielle E. Sklar,* Alex V. Helbling,* Yiqi Liu,* C. Wade Downey. One-Pot Synthesis of 2-Methylfurans from 3-(Trimethylsilyl)propargyl Acetates Promoted by Trimethylsilyl Trifluoromethanesulfonate. Tetrahedron Letters<\/em> 2021<\/strong>, 87<\/em>, Article 153424. link<\/a><\/p>\n 18. C. Wade Downey, Grace Ann L. Robertson,* Jhonmattew Santa,* Kari. R. Flicker,* William M. Stith.* One-pot silyl ketene imine formation-nucleophilic addition reactions of acetonitrile with acetals and nitrones. Tetrahedron Letters<\/em> 2020<\/strong>, 61<\/em>, Article 151537. \u00a0link<\/a><\/p>\n 17. C. Wade Downey, Grant J. Dixon,* Jared A. Ingersoll,* Claire N. Fuller,* Kenneth W. MacCormac,* Anna Takashima,* Rohina Sediqui.* One-pot enol silane formation-Mukaiyama aldol reactions: crossed aldehyde-aldehyde coupling, thioester substrates, and reactions in ester solvents. Tetrahedron Letters<\/em> 2019<\/strong>, 60<\/em>, Article 151192. \u00a0link<\/a><\/p>\n 16. C. Wade Downey, Danielle N. Confair,* Yiqi Liu,* Elizabeth D. Heafner.* One-Pot Enol Silane Formation-Alkylation of Ketones with Propargyl Carboxylates Promoted by Trimethylsilyl Trifluoromethanesulfonate. The Journal of Organic Chemistry<\/em> 2018<\/strong>, 83<\/em>, 12931-12938. \u00a0link<\/a><\/p>\n 15. C. Wade Downey, Hadleigh M. Glist,* Anna Takashima,* Samuel R. Bottum,* Grant J. Dixon.* Chalcone and cinnamate synthesis via one-pot enol silane formation-Mukaiyama aldol reactions of ketones and acetate esters. Tetrahedron Letters<\/em> 2018<\/strong>, 59<\/em>, 3080-3083. link<\/a><\/p>\n 14. C. Wade Downey, Alice Y.-K. Lee,* John R. Goodin,* Courtney J. Botelho,* William M. Stith.* Mukaiyama addition of (trimethylsilyl)acetonitrile to dimethyl acetals mediated by trimethylsilyl trifluoromethanesulfonate. Tetrahedron Letters<\/em> 2017<\/strong>, 58<\/em>, 3496-3499. link<\/a><\/p>\n 13. C. Wade Downey, Jared A. Ingersoll,* Hadleigh M. Glist,* Carolyn M. Dombrowski,* Adam T. Barnett.* One-pot silyl ketene acetal-formation-Mukaiyama\u2013Mannich additions to imines mediated by trimethylsilyl trifluoromethanesulfonate. European Journal of Organic Chemistry <\/em>2015<\/strong>, 7287-7291. link<\/a><\/p>\n 12. C. Wade Downey, Christopher D. Poff,* Alissa N. Nizinski.* Friedel\u2212Crafts Hydroxyalkylation of Indoles Mediatedby Trimethylsilyl Trifluoromethanesulfonate. The Journal of Organic Chemistry<\/em> 2015<\/strong>, 80<\/em>, 10364-10369. link<\/a><\/p>\n 11. 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<\/em> 2014<\/strong>, 55<\/em>, 5213-5215. link<\/a><\/p>\n 10. C. Wade Downey, Erin N. Maxwell,* Danielle N. Confair* Silyl Triflate-Accelerated Additions of Catalytically Generated Zinc Acetylides to N-Phenyl Nitrones. Tetrahedron Letters<\/em> 2014<\/strong>, 55<\/em>, 4959-4961. link<\/a><\/p>\n 9. C. Wade Downey, Carolyn M. Dombrowski,* Erin N. Maxwell,* Chelsea L. Safran,* Odamea A. Akomah.* One-Pot Enol Silane Formation-Mukaiyama\u2013Mannich Addition of Ketones, Amides, and Thioesters to Nitrones in the Presence of Trialkylsilyl Trifluoromethanesulfonates. European Journal of Organic Chemistry<\/em> 2013<\/strong>, 5716-5720. link<\/a><\/p>\n 8. Lutz F. Tietze, Holger Geissler, C. Wade Downey. \u201cDiethyl Ethoxymethylenemalonate\u201d In Encyclopedia of Reagents in Organic Synthesis [Online] 2013, Tomislav Rovis, Ed.; Wiley & Sons: New York.<\/p>\n 7. C. Wade Downey, Smaranda Craciun,* Christina A. Vivelo,* Ana M. Neferu,* Carly J. Mueller,* Stephanie Corsi.* One-Pot Three-Step Thioconjugate Addition-Oxidation-Diels\u2013Alder Reactions of Ethyl Propiolate. Tetrahedron Letters<\/em> 2012<\/strong>, 53<\/em>, 5766-5768. link<\/a><\/p>\n 6. 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)-\uf062-Sulfonyl Enoates from Ethyl Propiolate. Tetrahedron Letters <\/em>2012<\/strong>, 53<\/em>, 5763-5765. link<\/a><\/p>\n 5. C. Wade Downey, Alan S. Fleisher,* James T. Rague,* Chelsea L. Safran,* Megan E. Venable,* Robert D. Pike. Synthesis of N-Acyl-N,O-Acetals from N-Aryl Amides and Acetals in the Presence of TMSOTf. Tetrahedron Letters<\/em> 2011<\/strong>, 52<\/em>, 4756-4759. link<\/a><\/p>\n 4. 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. The<\/em> Journal of Organic Chemistry<\/em> 2010<\/strong>, 75<\/em>, 5351-5354. link<\/a><\/p>\n 3. C. Wade Downey, Brian D. Mahoney,* Vincent R. Lipari.* Trimethylsilyl Trifluoromethanesulfonate-Accelerated Addition of Catalytically Generated Zinc Acetylides to Aldehydes. The Journal of Organic Chemistry<\/em> 2009<\/strong>, 74<\/em>, 2904-2906. link<\/a><\/p>\n 2. C. Wade Downey, Miles W. Johnson,* Kathryn J. Tracy.* One-Pot Enol Silane Formation-Mukaiyama Aldol-Type Addition to Dimethyl Acetals Mediated by TMSOTf. The Journal of Organic Chemistry<\/em> 2008<\/strong>, 73<\/em>, 3299-3302. link<\/a><\/p>\n 1. C. Wade Downey, Miles W. Johnson.* A Tandem Enol Silane Formation-Mukaiyama Aldol Reaction Mediated by TMSOTf. 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\nOur work is currently funded by generous contributions from the Camille & Henry Dreyfus Foundation and the University of Richmond. Previous sources of funding include the National Science Foundation, The American Chemical Society-Petroleum Research Fund, Research Corporation, Organic Syntheses, Inc., and the Thomas F. and Kate Miller Jeffress Trust.<\/p>\n
\nUniversity of Richmond undergraduate coauthors are denoted with an asterisk (*).<\/strong><\/p>\n