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

Abstract

AbstractTrifluoromethyl 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.