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

doi:10.1002/ejoc.202001071

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

Authors

Ben J. Murray

Thomas G.F. Marsh

Dr Dmitry Yufit d.s.yufit@durham.ac.uk
Academic Visitor

Dr Mark Fox m.a.fox@durham.ac.uk
Assistant Professor

Antal Harsanyi

Lee T. Boulton

Graham Sandford

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

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