HFO‐1234yf as a CF3 Building Block: Synthesis of Trifluoromethyl Quinoline and Chromene Derivatives from Trifluoromethyl‐ynones

Marsh, Thomas G.F.; Santambrogio, Alessia; Murray, Ben J.; Boulton, Lee T.; Aguilar, Juan A.; Yufit, Dmitry S.; Sandford, Graham; Brittain, William D.G.

Abstract

Trifluoromethyl ynones derived from the refrigerant gas HFO-1234yf (2,3,3,3-tetrafluoropropene) react with nucleophiles via a Michael-type addition process and the allenolate intermediate formed reacts intramolecularly with a carbonyl group to form heterocyclic derivatives. Thus, reaction of 2-amino and 2-hydroxyl benzaldehyde or ketone substrates with trifluoromethyl ynone derivatives gives trifluoromethyl quinoline and chromene products by a one-pot tandem ring closing sequence, forming pharmaceutically relevant structures from an inexpensive starting material without the need for transition metals or column chromatography. The 2-trifluoromethylquinoline products also show unusual fluxional behaviour, which was explored through 2-D NMR and X-ray crystallographic studies.

Citation

Marsh, T. G., Santambrogio, A., Murray, B. J., Boulton, L. T., Aguilar, J. A., Yufit, D. S., …Brittain, W. D. (2023). HFO‐1234yf as a CF3 Building Block: Synthesis of Trifluoromethyl Quinoline and Chromene Derivatives from Trifluoromethyl‐ynones. European Journal of Organic Chemistry, 26(11), Article e202300058. https://doi.org/10.1002/ejoc.202300058

• Journal Article Type: Article
• Acceptance Date: Jan 24, 2023
• Online Publication Date: Feb 15, 2023
• Publication Date: 2023-03
• Deposit Date: Feb 24, 2023
• Publicly Available Date: May 30, 2023
• Journal: European Journal of Organic Chemistry
• Print ISSN: 1434-193X
• Electronic ISSN: 1099-0690
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 11
• Article Number: e202300058
• DOI: https://doi.org/10.1002/ejoc.202300058