Copper Complexes of Anionic Nitrogen Ligands in the Amidation and Imidation of Aryl Halides

Abstract

Copper(I) imidate and amidate complexes of chelating N,N-donor ligands, which are proposed intermediates in copper-catalyzed amidations of aryl halides, have been synthesized and characterized by X-ray diffraction and detailed solution-phase methods. In some cases, the complexes adopt neutral, three-coordinate trigonal planar structures in the solid state, but in other cases they adopt an ionic form consisting of an L 2 Cu + cation and a CuX 2 − anion. A tetraalkylammonium salt of the CuX 2 − anion in which X = phthalimidate was also isolated. Conductivity measurements and 1 H NMR spectra of mixtures of two complexes all indicate that the complexes exist predominantly in the ionic form in DMSO and DMF solutions. One complex was sufficiently soluble for conductance measurements in less polar solvents and was shown to adopt some degree of the ionic form in THF and predominantly the neutral form in benzene. The complexes containing dative nitrogen ligands reacted with iodoarenes and bromoarenes to form products from C-N coupling, but the ammonium salt of [Cu(phth) 2 ] − did not. Similar selectivities for stoichiometric and catalytic reactions with two different iodoarenes and faster rates for the stoichiometric reactions implied that the isolated amidate and imidate complexes are intermediates in the reactions of amides and imides with haloarenes catalyzed by copper complexes containing dative N,N ligands. These amidates and imidates reacted much more slowly with chloroarenes, including chloroarenes that possess more favorable reduction potentials than some bromoarenes and that are known to undergo fast dissociation of chloride from the chloroarene radical anion. The reaction of o-(allyloxy)iodobenzene with [(phen) 2 Cu][Cu(pyrr) 2 ] results in formation of the C-N coupled product in high yield and no detectable amount of the 3-methyl-2,3-dihydrobenzofuran or 3-methylene-2,3-dihydrobenzofuran products that would be expected from a reaction that generated free radicals. These data and computed reaction barriers argue against mechanisms in which the haloarene reacts with a two-coordinate anionic copper species and mechanisms that start with electron transfer to generate a free iodoarene radical anion. Instead, these data are more consistent with mechanisms involving cleavage of the carbon-halogen bond within the coordination sphere of the metal.

Copper(I) Phenoxide Complexes in the Etherification of Aryl Halides

“…Moreover, we have conducted computational studies by DFT on the energy of a phen-ligated arylcopper(III) halide phenoxide complex, and the ΔG for formation of this species from the [Cu(phen)(OPh)] and PhI is computed to be 22.1 kcalmol −1 [Eq. (10)]. This energy is consistent with the barrier corresponding to the conditions of the experiments in Eq.…”

“…[9] Only recently have any isolated copper complexes been evaluated as intermediates in copper-catalyzed coupling reactions. [10,11] In one recent study, copper(I) imidates and amidates were isolated in pure form, structurally characterized, and shown to be intermediates in related copper-catalyzed Goldberg reactions, [10] and in another study kinetic data were obtained on copper amidates generated in situ. [12,13] The relationship between intermediates in copper-catalyzed coupling reactions that form C-N bonds and potential intermediates in couplings that form C-O bonds is unknown.…”

Theoretical Investigations on Deactivation of Copper Catalytic Species in Ullmann Cross Coupling Reactions

“…Calculated free energy barriers for free radical formation are very high (93 kcal/mol). It is much higher than energy barrier reported for OA pathway [18]. Calculated free energy indicates that the oxidation of Cu(I) through free radical pathway is not possible.…”

“…Hartwig and co-workers [18] have demonstrated that species A do not participate in reactions. It was proposed that species A are inert off cycle species and responsible for deactivation of copper and high demand of Cu/ligand system.…”

Understanding the Heteroatom Effect on the Ullmann Copper-Catalyzed Cross-Coupling of X-Arylation (X = NH, O, S) Mechanism

“…They clearly showed that the aryl halide activation occurs by the [(L)Cu I (Nu)] complexes. In this regard, Hartwig et al were able to isolate and characterize a number of copper imidate, amidate, amino, phenoxide, and thiophenoxide complexes which are chemically competent to couple a variety of aryl halides [40,42,56]. The studies carried out on the reactivity of these complexes, including kinetic studies and radical clock experiments, argued against pathways involving radical intermediates.…”