HFO-1234yf as a CF3-building block: Synthesis and Chemistry of CF­3-ynones

Murray, Ben J.; Marsh, Thomas G.F.; Yufit, Dmitri S.; Fox, Mark A.; Harsanyi, Antal; Boulton, Lee T.; Sandford, Graham

Abstract

Reaction of low cost, readily available 4th generation refrigerant gas 2,3,3,3‐tetrafluoropropene (HFO‐1234yf) with lithium diisopropylamide (LDA) leads to formation of lithium 3,3,3‐trifluoropropynide, addition of which to a range of aldehydes formed CF3‐alkynyl alcohol derivatives on multigram scale, which were oxidised using Dess‐Martin periodinane (DMP) to give substituted CF3‐ynones with minimal purification required. Michael‐type additions of alcohol and amine nucleophiles to CF3‐ynones are rapid and selective, affording a range of CF3‐enone ethers and enaminones in excellent yields with high stereoselectivity for the Z‐isomer. By analogous reactions with difunctional nucleophiles, a wide range of CF3‐substituted pharmaceutically relevant heterocyclic structures can be accessed, exemplified in the simple synthesis of the anti‐arthritis drug celecoxib from HFO‐1234yf in just three steps.

Citation

Murray, B. J., Marsh, T. G., Yufit, D. S., Fox, M. A., Harsanyi, A., Boulton, L. T., & Sandford, G. (2020). HFO-1234yf as a CF3-building block: Synthesis and Chemistry of CF­3-ynones. European Journal of Organic Chemistry, 2020(39), 6236-6244. https://doi.org/10.1002/ejoc.202001071

• Journal Article Type: Article
• Acceptance Date: Aug 12, 2020
• Online Publication Date: Sep 10, 2020
• Publication Date: 2020-10
• Deposit Date: Aug 18, 2020
• Publicly Available Date: Sep 16, 2020
• Journal: European Journal of Organic Chemistry
• Print ISSN: 1434-193X
• Electronic ISSN: 1099-0690
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 2020
• Issue: 39
• Pages: 6236-6244
• DOI: https://doi.org/10.1002/ejoc.202001071
• Public URL: https://durham-repository.worktribe.com/output/1258251