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

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 2hydroxyl 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.

Microwave-assisted DABCO-promoted regioselective [3 + 3] tandem cyclization: synthesis of pyrrolo[3,4-b]pyridine-4-ones from trifluoromethyl-alkynyl esters and α-aminomaleimide

“…To gain insight into the reaction mechanism, various mechanistic experiments were performed, 21 and we proposed the reaction control experiment, as shown in Scheme 3. Firstly, we verified the final structure of the reaction.…”

Recent advances in the synthesis of trifluoromethyl-containing heterocyclic compounds via trifluoromethyl building blocks

“…In 2023, Brittain et al 31 showed that trifluoromethyl ynones obtained from a refrigerant gas feedstock (HFO-1234yf ) can be easily transformed into various substituted Organic & Biomolecular Chemistry Review a nucleophilic reagent. The resulting allenolate intermediate then undergoes an intramolecular reaction to produce CF 3heterocyclic derivatives.…”