University of California

Other

University of Illinois

Patrick Fier

John F Hartwig

Hiroyuki Morimoto

A composition, consisting essentially of copper, a fluoroalkyl group, and a ligand comprising at least one group-V donor. The molar ratio of copper to the fluoroalkyl group is approximately 1.

One-component reagent for the fluoroalkylation reaction

The present invention provides compositions and methods for the selective C&#x2014;H fluorination of nitrogen-containing heteroarenes with AgF, which has previously been considered too reactive for practical, selective C&#x2014;H fluorination. Fluorinated heteroarenes are prevalent in numerous pharmaceuticals, agrochemicals and materials. However, the reactions used to introduce fluorine into these molecules require pre-functionalized substrates or the use of Fgas. The present invention provides a mild and general method for the C&#x2014;H fluorination of nitrogen-containing heteroarene compounds to 2-fluoro-heteroarenes with commercially available AgF. In various embodiments, these reactions occur at ambient temperature within one hour and occur with exclusive selectivity for fluorination at the 2-position. Exemplary reaction conditions are effective for fluorinating diazine heteroarenes to form a single fluorinated isomer.

C-H fluorination of heterocycles with silver (II) fluoride

Selectively fluorinated molecules are important as materials, pharmaceuticals, and agrochemicals, but their synthesis by simple, mild, laboratory methods is challenging. We report a straightforward method for the cross-coupling of a difluoromethyl group with readily available reagents to form difluoromethylarenes. The reaction of electron-neutral, electron rich, and sterically hindered aryl and vinyl iodides with the combination of CuI, CsF and TMSCFH leads to the formation of difluoromethylarenes in high yield with good functional group compatibility. This transformation is surprising, in part, because of the prior observation of the instability of CuCFH.

Difluoromethylation of aryl and vinyl iodides

The invention provides compositions and methods of using the compositions in fluorinating aryl precursors containing a leaving group replaceable by fluoride ion. The compositions include a metal ion source, a fluoride ion source, and a compound, which is an aryl precursor of the aryl fluoride, and which has a leaving group replaceable by the fluoride. Exemplary methods of the invention make use of such compositions and methods to prepare an aryl fluoride compound. In an exemplary embodiment, the fluoride ion source is a source ofF.

Fluorination of aryl compounds

A method of forming a fluorinated molecular entity includes reacting in a reaction mixture an aromatic halide, copper, a fluoroalkyl group, and a ligand. The aromatic halide includes an aromatic group and a halogen substituent bonded to the aromatic group. The ligand includes at least one group-V donor selected from phosphorus and an amine. The overall molar ratio of copper to aromatic halide in the reaction mixture is from 0.2 to 3. The method further includes forming a fluoroalkylarene including the aromatic group and the fluoroalkyl group bonded to the aromatic group. A composition, which may be used in the method, consists essentially of copper, the fluoroalkyl group, and the ligand, where the molar ratio of copper to the fluoroalkyl group is approximately 1.

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Berkeley, CA, United States of America

Patrick Fier