HFO-1234yf as a CF3 Building Block: Synthesis of Trifluoromethyl Quinoline and Chromene Derivatives from Trifluoromethyl-ynones |
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Authors: | Thomas G. F. Marsh Alessia Santambrogio Dr. Ben J. Murray Dr. Lee T. Boulton Dr. Juan A. Aguilar Dr. Dmitry S. Yufit Prof. Graham Sandford Dr. William D. G. Brittain |
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Affiliation: | 1. Department of Chemistry, Durham University, South Road, DH1 3LE Durham, UK;2. GlaxoSmithKline R&D Ltd, Medicines Research Centre, Gunnels Wood Road, SG1 2NY Stevenage, Hertfordshire, UK |
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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. |
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Keywords: | We thank Durham University Mchem programme for funding to T. G. F. M. and A. S. and GlaxoSmithKline/EPSRC for the award of an iCASE studentship to B. J. M. W. D. G. B. would like to thank the Leverhulme Trust for an Early Career Fellowship (ECF-2020-454 and Durham University). |
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