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Polyfluorinated substituents often enhance effectiveness, improve the stability within metabolic processes, and boost the lipophilicity of biologically active compounds. However, methods for their introduction into aliphatic carbon chains remain very limited. A potentially general route to integrate the fluorinated scaffolds into organic molecules involves insertion of fluorine-containing carbenes into C(sp 3 )-H bonds. The electron-withdrawing characteristics of perfluoroalkyl groups enhances the reactivity of these carbenes which should enable the functionalization of unactivated C(sp 3 )-H bonds. Curiously, it appears that use of perfluoroalkyl-containing carbenes in alkane C-H functionalization is exceedingly rare. This concept describes photolysis, enzymatic catalysis, and transition metal catalysis as three primary approaches to C(sp 3 )-H functionalization by trifluoromethylcarbene and its homologues., (© 2023 Wiley‐VCH GmbH.)

We report here "sandwich"-diimine copper complex-catalyzed trifluoroethylation and pentafluoropropylation of unactivated C(sp 3 )-H bonds in alkyl esters, halides, and protected amines by employing CF 3 CHN 2 and CF 3 CF 2 CHN 2 reagents. Reactions proceed in dichloromethane solvent at room temperature. Identical C-H functionalization conditions and stoichiometries are employed for generality and convenience. Selectivities for C-H insertions are higher for compounds possessing stronger electron-withdrawing substituents. Preliminary mechanistic studies point to a mechanism involving a pre-equilibrium forming a "sandwich"-diimine copper-CF 3 CHN 2 complex followed by rate-determining loss of nitrogen affording the reactive copper carbene. It reacts with trifluoromethyldiazomethane about 6.5 times faster than with 1-fluoroadamantane explaining the need for slow addition of the diazo compound., (© 2023 Wiley-VCH GmbH.)

We report here "sandwich" diimine-copper(I) catalysts for C(sp 3 )-H bond functionalization. Reactions of alkanes and ethers with trimethylsilyldiazomethane, ethyl diazoacetate, and trifluoromethyl-diazomethane have been demonstrated. We also report C(sp 3 )-H bond methylation, benzylation, and diphenylmethylation by diazomethane, aryldiazomethanes, and diphenyldiazomethane. These reactions are rare examples of base-metal catalyzed, intermolecular C(sp 3 )-H functionalizations by employing unactivated diazo compounds. Electrophilicity and unique steric environment of "sandwich"-copper catalysts are likely reasons for their catalytic efficiency., (© 2022 Wiley-VCH GmbH.)

The reactivity of Ni II and Pd II olefin polymerization catalysts can be enhanced by introduction of electron-withdrawing substituents on the supporting ligands rendering the metal centers more electrophilic. Reported here is a comparison of ethylene polymerization activity of a classical salicyliminato nickel catalyst substituted with the powerful electron-withdrawing 2,4,6-triphenylpyridinium (trippy) group to the -CF 3 analogue. The trippy substituent is substantially more electron-withdrawing (σ meta =0.63) than the trifluoromethyl group (σ meta =0.43) which results in a ca. 8-fold increase in catalytic turnover frequency. An additional advantage of trippy is the high steric bulk relative to the trifluoromethyl group. This feature results in a four-fold increase in polymer molecular weight owing to enhanced retardation of chain transfer. A significant increase in catalyst lifetime is observed as well., (© 2020 Wiley-VCH GmbH.)

A method for cobalt-catalyzed, carboxylate-directed functionalization of arene C-H bonds is reported. Alkynes, styrenes, and 1,3-dienes can be coupled with benzoic acids to provide cyclic products in good yields. The reactions proceed in the presence of a cobalt(II) hexafluoroacetylacetonate catalyst, (TMS) 2 NH base, Ce(SO 4 ) 2 cooxidant, and oxygen oxidant., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We have developed a method for palladium-catalyzed, pyrazole-directed sp 3 C-H bond arylation by aryl iodides. The reaction employs a Pd(OAc) 2 catalyst at 5-10 mol % loading and silver(I) oxide as a halide-removal agent, and it proceeds in acetic acid or acetic acid/hexafluoroisopropanol solvent. Ozonolysis of the pyrazole moiety affords pharmaceutically important β-phenethylamines., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report structural characterization of a new member of m-phenylene ethynylene ring family. This shape-persistent macrocycle also co-crystallizes with hexafluoro-, 1,2,4,5-tetrafluoro-, 1,3,5-trifluoro, and 1,4-difluorobenzene. The four complexes are almost isostructural, and all show the fluoroarene included into the central cavity of the macrocycle. Characterized by multiple short C - H⋅⋅⋅F - C contacts, these inclusion complexes further dimerize in the solid state into a 2+2 assembly, in which the two macrocycles embrace each other by their large hydrophobic groups that are rotated by 60° relative to one another., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A method for cobalt-catalyzed, aminoquinoline- and picolinamide-directed C(sp(2))-H bond alkenylation by alkynes was developed. The method shows excellent functional-group tolerance and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs a Co(OAc)2⋅4 H2O catalyst, Mn(OAc)2 co-catalyst, and oxygen (from air) as a terminal oxidant., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Amine meets arene: A method for direct amination of β-C(sp(2))-H bonds of benzoic acid derivatives and γ-C(sp(2))-H bonds of benzylamine derivatives has been developed. The reaction is catalyzed by Cu(OAc)2 and a Ag2CO3 cocatalyst, and shows high generality and functional-group tolerance, as well as providing a straightforward means for the preparation of ortho-aminobenzoic acid derivatives., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)