The regioselective
C–H trifluoromethylthiolation of six-membered
heteroaromatic compounds via nucleophilic attack of a CF3S source on the electrophilically activated six-membered heteroaromatic
ring was developed. The reaction proceeds in good yield with good
functional group tolerance, even on a gram-scale. The key to the successful
regioselective transformation is the presence of an additive (2,4-dinitrobenzenesulfonyl
chloride). The regioselective trifluoromethylthiolation of quinidine
derivative is also demonstrated. Trifluoromethylthiolation, followed
by S-oxidation, affords the corresponding sulfones.
The first example of the 3-position-selective C(sp2)–H
trifluoromethylation of pyridine rings was established. 3-Position-selective
trifluoromethylation was achieved by the nucleophilic activation of
pyridine and quinoline derivatives through hydrosilylation and successive
electrophilic trifluoromethylation of the enamine intermediate. This
reaction was applicable to perfluoroalkylation at the 3 position of
the pyridine rings and late-stage trifluoromethylation of a bioactive
molecule. Mechanistic studies indicated that the reaction proceeds
via the formation of N-silyl enamine and trifluoromethylated
enamine intermediates.
A β-monofluoromethylated vinyl sulfonium salt, prepared in situ from a precursor γ-fluoro β-acetoxypropyl sulfonium salt under mild basic conditions, reacted with a lvariety of active methylene compounds or a primary sulfone amide under basic conditions to provide the corresponding monofluoromethylated three-membered rings in good-to-excellent yields. This new sulfonium reagent should permit easy access to a variety of important monofluoromethylated organic compounds.
The first example of the 3-position-selective C(sp2)–H trifluoromethylation of pyridine rings was established. 3-Position-selective trifluoromethylation was achieved by the nucleophilic activation of pyridine and quinoline derivatives through hydrosilylation and successive electrophilic trifluoromethylation of the enamine intermediate. This reaction was applicable to perfluoroalkylation at the 3-position of the pyridine rings and late-stage trifluoromethylation of a bioactive molecule. Mechanistic studies indicated that the reaction proceeds via the formation of N-silyl enamine and trifluoromethylated enamine intermediates.
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