Copper-catalyzed Goldberg-type C–N coupling in deep eutectic solvents (DESs) and water under aerobic conditions

Abstract

A scalable CuI-catalyzed Goldberg C–N coupling between aryl iodides and amides is reported either in DESs or in water.

Ligand‐Free Copper‐Catalyzed Ullmann‐Type C−O Bond Formation in Non‐Innocent Deep Eutectic Solvents under Aerobic Conditions

“…Despite the recommendations of institutions and organizations like the Green Chemistry Institute Pharmaceutical Roundtable (GCIPR), the European Union, and the United States Environmental Protection Agency (EPA) about the need to replace conventional hazardous VOCs with safer and bio‐based media, [19] there are still very few examples of the employment of DESs in the synthesis of active pharmaceutical ingredients (APIs). [ 13d , 13f , 13j , 14j , 15b , 20 ] Aryloxypropanediols are prevalent motifs in pharmaceutically relevant compounds such as Guaiphenesin ( 2 o ), [21] an expectorant drug useful in patients with stable chronic bronchitis, Mephenesin (Tolseron) ( 2 p ), [22] used to treat muscle spasticity in Parkinson's disease and multiple sclerosis, and Chlorphenesin ( 2 q ), [23] used as muscle relaxant and as antifungal agent and biocide in cosmetics (Scheme 3 ).…”

“… [9] In 2014, Chae and co‐workers [10] described an efficient Cu II ‐catalyzed C−O coupling between aryl bromides and iodides and aliphatic diols (which acted as reactants, ligands, and solvents) to generate the corresponding hydroxyalkyl aryl ethers, when working at 130 °C for 20 h, under an Ar atmosphere (Scheme 1 b). As part of our ongoing research program on the synthesis of heterocycles [11] and on bio‐, [12] metal‐catalyzed, and metal‐mediated organic transformations [13] run in environmentally responsible solvents like water and deep eutectic solvents (DESs), [14] we recently introduced a general methodology for the direct Cu I ‐catalyzed C−N coupling reactions between aliphatic/aromatic amines [15a] or primary/secondary amides [15b] and (hetero)aromatic halides, taking place in a choline chloride/glycerol (ChCl/Gly) [15a] or in a ChCl/water (or even in water) [15b] eutectic mixture, under mild and bench‐type reaction conditions.…”

Scalable Negishi Coupling between Organozinc Compounds and (Hetero)Aryl Bromides under Aerobic Conditions when using Bulk Water or Deep Eutectic Solvents with no Additional Ligands

“…As part of our ongoing research in DES and water chemistry, we recently reshaped some transition metal‐catalyzed cross‐coupling reactions, like the Suzuki–Miyaura, [12a,b] the Sonogashira, [12c] and the Ullmann‐Goldberg couplings, [12d,e] and the aminocarbonylation of aryl iodides [12f] in bioinspired eutectic mixtures, and set up the direct Pd‐catalyzed cross‐coupling between organolithiums and (hetero)aryl halides, by using bulk water as a non‐innocent reaction medium in the presence of NaCl as a cheap additive [12g] . Herein, we report the Pd‐catalyzed NC between (hetero)aryl bromides and organozinc halides, and compare the outcome of the reactions both in DESs and in water/NaCl.…”

Ligand‐ and Base‐Free Cu‐Catalyzed C−N Coupling of Aminoquinolines with Boronic Acids

“…[8] The exhaustive refinement of copper-catalyzed carbon-nitrogen coupling reactions has been progressing since the first report by Ullmann and Goldberg. [9,10,11,12] Moreover, tremendous growth in the application of copper-catalyzed protocols in organic synthesis was witnessed after the pioneering works of Taillefer and Buchwald. [13,14] Their discoveries opened new avenues for the Cu-based coupling reactions which previously suffered from harsh reaction conditions like high temperature (> 200°C), high catalyst loading, necessity of polar solvents, long reaction times and poor functional group tolerance.…”

“…The utility of copper‐based coupling reactions has been significantly enhanced by the execution of mild reaction conditions and the ability to make use of catalytic amounts of copper [8] . The exhaustive refinement of copper‐catalyzed carbon‐nitrogen coupling reactions has been progressing since the first report by Ullmann and Goldberg [9,10,11,12] . Moreover, tremendous growth in the application of copper‐catalyzed protocols in organic synthesis was witnessed after the pioneering works of Taillefer and Buchwald [13,14] .…”