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

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.

Automated summary

Trifluoromethyl ynones derived from HFO-1234yf react with nucleophiles and form heterocyclic derivatives via intramolecular reactions. The reaction with 2-amino and 2-hydroxyl benzaldehyde or ketone substrates gives trifluoromethyl quinoline and chromene products, offering a simple and economical approach to pharmaceutically relevant structures. The unusual fluxional behavior of the 2-trifluoromethylquinoline products is studied through 2-D NMR and X-ray crystallography.