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An Organocopper(III) Fluoride Triggering C−CF<sub>3</sub> Bond Formation

Daniel Joven‐Sancho, Andrea Echeverri, Nathalie Saffon‐Merceron, Julia Contreras‐García, Noel Nebra

2023Angewandte Chemie International Edition14 citationsDOIOpen Access PDF

Abstract

Abstract Copper(III) fluorides are catalytically competent, yet elusive, intermediates in cross‐coupling. The synthesis of [PPh 4 ][Cu III (CF 3 ) 3 F] ( 2 ), the first stable (isolable) Cu III −F, was accomplished via chloride addition to [Cu III (CF 3 ) 3 (py)] ( 1 ) yielding [PPh 4 ][Cu III (CF 3 ) 3 Cl(py)] ( 1 ⋅Cl), followed by treatment with AgF. The Cu III halides 1 ⋅Cl and 2 were fully characterized using nuclear magnetic resonance (NMR) spectroscopy, single crystal X‐ray diffraction (Sc‐XRD) and elemental analysis (EA). Complex 2 proved capable of forging C−CF 3 bonds from silyl‐capped alkynes. In‐depth mechanistic studies combining probes, theoretical calculations, trapping of intermediate 4 a ([PPh 4 ][Cu III (CF 3 ) 3 (C≡CPh)]) and radical tests unveil the key role of the Cu III acetylides that undergo facile 2 e − reductive elimination furnishing the trifluoromethylated alkynes (RC≡CCF 3 ), which are industrially relevant synthons in drug discovery, pharma and agrochemistry.

Topics & Concepts

ChemistrySynthonHalideSilylationReductive eliminationMedicinal chemistryNuclear magnetic resonance spectroscopyCopperFluorideSingle crystalCrystal structureChlorideCrystallographyStereochemistryInorganic chemistryCatalysisOrganic chemistryFluorine in Organic ChemistryInorganic Fluorides and Related CompoundsCatalytic C–H Functionalization Methods