A simple base-mediated synthesis of diverse functionalized ring-fluorinated 4H-pyrans via double direct C–F substitutions

Abstract

A straightforward and efficient approach to structurally diverse and synthetically useful ring-fluorinated 4H-pyrans via a simple base-mediated cascade reaction of readily available trifluoromethylated alkenes with 1,3-dicarbonyl compounds was developed. The key events of this reaction involve two consecutive C-F substitutions under very mild conditions.

Facile Synthesis of Unsymmetrical 2,5‐Disubstituted 1,3,4‐Oxadiazoles by Cyclization of gem‐Difluoroalkenes with Acyl Hydrazides

“…[17,18] These novel protocols provide attractive and complementary methods for the construction of various carbocycles and heterocycles from gem-difluoroalkenes and trifluoromethyl alkenes. [17,18] These novel protocols provide attractive and complementary methods for the construction of various carbocycles and heterocycles from gem-difluoroalkenes and trifluoromethyl alkenes.…”

Silver‐Catalyzed Double Hydrocarbonation of 2‐Trifluoromethyl‐1,3‐Conjugated Enynes with 1,3‐Dicarbonyl Compounds: Synthesis of Ring‐Trifluoromethylated Cyclopentene

“…We speculated that the competing readily defluorination of α‐CF 3 carbanions Int‐II formed via S N 2’ reaction of 2‐trifluoromethyl‐1,3‐enynes with 1,3‐dicarbonyl compounds under basic reaction conditions might be supressed by proper combination use of silver catalyst and a base (Scheme b), and trifluoromethylated allene intermediate Int‐III could prefer to be formed (Scheme c). We envisaged that this allene intermediate Int‐III could further undergo enolization under basic reaction conditions, followed by 6‐exo‐dig intramolecular heterocyclisation, with the nucleophilic oxygen attacking the central allene carbon atom would give another novel type of ring‐fluorinated heterocycle, that is ring‐trifluoromethylated 4 H ‐pyran 4 rather than ring‐monofluorinated 4 H ‐pyran (path b). To our surprise, unpredictable 5‐endo‐trig intramolecular hydrocarbonation, with the nucleophilic carbon attacking the distal allene carbon atom leading to trifluoromethylated cyclopentenes 3 rather than ring‐trifluoromethylated 4 H ‐pyrans 4 was observed (path a).…”

Methyl fluorosulfonyldifluoroacetate (MFSDA): An Underutilised Reagent for Trifluoromethylation

“…Recently, this strategy has been employed to synthesise trifluoromethylated alkenes required as starting materials by Yang et al. in the base‐mediated synthesis of ring‐fluorinated 4 H ‐pyrans …”