Copper-catalyzed Ullmann Coupling Research Articles

Tuning C-N Ullmann coupling with anion-exchanged ionic liquid-functionalized nanoparticle catalysts

Modern organic chemistry demands efficient and sustainable synthetic methods. Copper-catalyzed Ullmann coupling reactions, adept at constructing biaryl and aryl-heteroaryl motifs, have gained significant traction. However, traditional methods suffer from limitations. Nanoparticle catalysts, particularly copper nanoparticles (CuNPs), offer improved efficiency, but their performance is hampered by agglomeration and leaching. Hybrid supports incorporating ionic liquids (ILs) address this issue by providing a polar environment stabilizing CuNPs and enhancing catalytic activity and selectivity. This study investigates the impact of anion exchange in ionic liquids on the catalytic performance of C-N Ullmann couplings. Anion exchange modifies interionic interactions, hydrogen bonding, and dipolar properties, ultimately influencing the reaction's outcome. We synthesized CuNPs impregnated in silica supports functionalized with a triazolium-based ionic liquid possessing different anions (BF4−, PF6−, NTf2−) to elucidate the effect of anion exchange.Characterization techniques like FT-IR, XPS, TGA, and XPS confirmed successfully incorporating the triazole group and varying anions onto the material. TEM analysis showed the presence of CuNPs (4.5–5.7 nm) impregnated on the triazole functionalized silica supports.Catalytic studies yielded fascinating insights into the impact of different anions on conversion and selectivity. Iodide (I−) promoted higher conversion (100%), while tetrafluoroborate (BF4−) offered superior selectivity (57%). Computational studies provided valuable explanations, shedding light on the reactivity of the nanostructures and the interaction mechanism between substrates and the nanocatalyst. The theoretical results suggest that coordinative covalent bonds and highly polarized interactions govern the substrate interaction, with the aniline path achieving higher stabilization.Furthermore, the choice of anion influences the reactivity, substrate stabilization, and spin density distribution. These properties directly correlate with the conversion and selectivity observed in the catalytic studies.

Azaindole based fluorescent chemosensors for detecting Fe(II/III) ions and molecular logic gate implementation

A series of tridentate polypyridyl N^N^N/N^C^N-coordinating ligands (R1, L1, L2) were synthesized by copper-catalyzed Ullmann coupling (C–N bond-forming) reaction in moderate yields (∼50 %). Two charged ligands, L3 and L4 were also synthesized by methylation of L1 and L2 in moderate yields (∼45 %). These ligands were characterized by a set of analytical techniques including NMR, HRMS and single-crystal XRD. The electrochemical and photophysical properties of these ligands were examined using cyclic voltammetry, UV–vis absorption and luminescence spectroscopies. Theoretical calculations in the level of DFT and TD-DFT were also performed for the detailed studies of the optoelectronic properties of these compounds. These ligands displayed either an admixture of singlet ligand-centered (1LC) and singlet charge-transfer (1CT) transitions or pure 1LC/1CT luminescence in some cases. Ligands R1 and L1 which were highly emissive were further used as selective chemosensors for the detection of Fe(II)/(III) with a “turn-off” fluorescence behavior in a binding stoichiometry of 2:1 = ligand: M(II/III) [M = Fe(II)/Fe(III)] and a limit of detection up to 0.87–1.19 ppm level. L1 was also realized for the successful construction of the molecular logic gate.

Betti Base as an Efficient Ligand for Copper-Catalyzed Ullmann Coupling of Phenol with Aryl Halides

A simple, general, and highly efficient Betti base ligand has been developed for copper-catalyzed Ullmann coupling of phenol with aryl halides without the protection of an inert atmosphere. The reaction proceeds smoothly in the presence of K2CO3 as the base and dimethylsulfoxide as the solvent. The catalyst was reused several times with no evident loss of catalytic activity and is environmentally friendly.

Copper-catalyzed intramolecular tandem reaction of (2-halogenphenyl)(3-phenyloxiran-2-yl)methanones: synthesis of (Z)-aurones.

A convenient and efficient method for the copper-catalyzed synthesis of (Z)-aurones via intramolecular tandem reaction of (2-halogenphenyl)(3-phenyloxiran-2-yl)methanones is reported. Moreover, a plausible mechanism for the formation of (Z)-aurones is proposed. This is the first report on the synthesis of (Z)-aurones through copper-catalyzed Ullmann coupling reaction employing epoxides as substrates.

Synthesis of Quinazolinones by Combined Ullmann Coupling-Oxidative C-H Amidation

Reported is an efficient synthesis of quinazolinone derivatives from substituted 2-halobenzamides 1 and (aryl)methanamines 2 through a sequential copper-catalyzed Ullmann coupling and aerobic oxidative C-H amidation. Screening of bases, catalysts, solvents, and reaction temperature led to the optimized CuBr/K2CO3 catalyst-base combination. As expected, 2-iodobenzamides show higher reactivity than the corresponding bromides; further, only aryl chlorides containing EWGs were effective coupling partners. In general, the nature of the substituent (EWGs or EDGs) on the halobenzamides or (aryl)-methanamines was inconsequential to reactivity and ether, Cl, NO2 functional groups as well as ­nitrogen, oxygen or sulfur heterocyles were well tolerated in the amine component.

Total Synthesis of the Aspercyclides

Two different approaches to the eleven-membered biaryl ether lactones of the aspercyclide family are disclosed. The core regions of these highly strained targets, which are able to interfere with the binding of immunoglobulin E to its high affinity receptor, can either be forged by ring-closing olefin metathesis (RCM) or by a highly diastereoselective chromium-mediated Nozaki-Hiyama-Kishi (NHK) reaction. Whereas the RCM approach turned out to be responsive to minor changes in the substitution pattern of the substrate, the NHK route is more generally applicable. The preparation of the required cyclization precursor 43 hinged on a palladium-catalyzed ortho-iodination reaction of 2-methylbenzoic acid, an efficient copper-catalyzed Ullmann coupling, and a Takai-Utimoto olefination as the key steps. Moreover, the esterification of the 2,6-disubstituted benzoic acid 34 with the sterically hindered secondary alcohol 37 was far from trivial. However, this and related transformations were accomplished by recourse to the corresponding acid fluorides, which provided excellent yields in cases in which the more commonly used acid chlorides or mixed anhydrides failed to afford any of the desired products.

Synthesis of 2,5-Dihydrofuran-Fused Quinones from Ether-Tethered Diiododiyne

Biologically interesting 2,5-dihydrofuran-fused quinones were synthesized via the ruthenium-catalyzed [2 + 2 + 2] cycloaddition of an ether-tethered diiododiyne with alkynes, copper-catalyzed Ullmann coupling of the resultant fused p-diiodobenzenes with methanol or allyl alcohol, and subsequent oxidation of phenol derivatives. The double Claisen rearrangement of the bis(allyl) ether product furnished a diallylhydroquinone derivative, which underwent iron-catalyzed oxidation, ring-closing metathesis, and dehydrogenation to deliver 1,3-dihydronaphtho[2,3-c]furan-4,9-dione.

Copper-catalyzed Ullmann coupling under ligand- and additive-free conditions. Part 2: S-Arylation of thiols with aryl iodides

S-Arylation of a wide variety of substituted aryl and aliphatic thiols with aryl halides catalyzed by copper iodide under mild ligand- and additive-free conditions ( n Bu 4NBr, PhMe, NaOH, reflux, 22 h) is accomplished in good to excellent product yields (up to 96%).

Copper-catalyzed Ullmann coupling under ligand- and additive- free conditions. Part 1: O-Arylation of phenols with aryl halides

O-Arylation of a wide variety of substituted phenols and aliphatic alcohols with aryl halides catalyzed by copper iodide under mild ligand and additive free conditions ( n Bu 4NBr, DMF, K 3PO 4, reflux, 22 h) is accomplished in good to excellent product yields (up to 95%).

Synthesis of 4‐Methyl Pyrrolo[2,3‐b]xanthone, a Novel Ring System.

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Synthesis of 4‐Methyl Pyrrolo[2,3‐b]xanthone, a Novel Ring System

A short, high yielding synthesis of a novel substituted pyrrolo[2,3-b]xanthone has been developed. The synthesis begins with a copper catalyzed Ullmann coupling reaction followed by and intramolecular Friedel-Crafts acylation reaction to establish the xanthone core structure. After a regioselective nitration, a Leimgruber-Batcho synthesis establishes the final pyrrole ring.