Dr. Wade Downey
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Profile
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.
FUNDING
Our work is currently funded by generous contributions from the Camille & Henry Dreyfus Foundation, the Claude C. Gravatt and Ann S. Gravatt Endowed Fellowship, and the University of Richmond. Previous sources of funding include the National Science Foundation, Research Corporation, the American Chemical Society-Petroleum Research Fund, Organic Syntheses, Inc., and the Thomas F. and Kate Miller Jeffress Trust.
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Grants and Fellowships
Our work is currently funded by generous contributions from the Camille & Henry Dreyfus Foundation, the American Chemical Society-Petroleum Research Fund, Organic Syntheses, Inc., the Claude C. Gravatt and Ann S. Gravatt Endowed Fellowship, 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.
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Grants and Fellowships
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Publications
Journal Articles
*denotes undergraduate coauthor
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 2023, 128, Article 154718.
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 2023, 55, 2377-2389.
Grant J. Dixon,* Michael R. Rodriguez,* Tyler G. Chong,* Kevin Y. Kim,* C. Wade Downey. Synthesis of b,b-Disubstituted Styrenes via Trimethylsilyl Trifluoromethanesulfonate-Promoted Aldehyde-Aldehyde Aldol Addition-Deformylative Elimination. Journal of Organic Chemistry 2022, 87, 14846-14854.
Zachary Z. Oracheff,* Helen L. Xia,* Christopher D. Poff,* Scott E. Isaacson,* C. Wade Downey. Friedel–Crafts addition of indoles to nitrones promoted by trimethylsilyl trifluoromethanesulfonate Journal of Organic Chemistry 2021, 86, 17328-17336.
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 2021, 87, Article 153424.
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 2020, 61, 151537.
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 2019, 60, 151192.
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” Journal of Organic Chemistry 2018, 83, 12931-12938.
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 2018, 59, 3080-3083.
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 2017, 58, 3496-3499.
C. Wade Downey, Jared A. Ingersoll,* Hadleigh M. Glist,* Carolyn M. Dombrowski,* Adam T. Barnett* “One-pot silyl ketene acetal-formation-Mukaiyama–Mannich additions to imines mediated by trimethylsilyl trifluoromethanesulfonate” European Journal of Organic Chemistry 2015, 7287-7291.
C. Wade Downey, Christopher D. Poff,* Alissa N. Nizinski* “Friedel−Crafts Hydroxyalkylation of Indoles Mediatedby Trimethylsilyl Trifluoromethanesulfonate” 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.
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 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.
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