Copper-Catalyzed Coupling Reaction of (Hetero)Aryl Chlorides and Amides

Abstract

CuO/N,N'-bis(thiophen-2-ylmethyl)oxalamide is established to be an effective catalyst system for Goldberg amidation with inferior reactive (hetero)aryl chlorides, which have not been efficiently documented by Cu-catalysis to date. The reaction is well liberalized toward a variety of functionalized (hetero)aryl chlorides and a wide range of aromatic and aliphatic primary amides in good to excellent yields. Furthermore, the arylation of lactams and oxazolidinones is achieved. The present catalytic system also accomplished an intramolecular cross-coupling product.

Replacement of Less-Preferred Dipolar Aprotic and Ethereal Solvents in Synthetic Organic Chemistry with More Sustainable Alternatives

“…Water has also been successfully utilized as reaction solvent in related Cu-catalyzed Ullman-type reactions, 286 as have other safer solvents such as tBuOH. 287 Solvent-free examples are also known. 288 …”

Recent Advances in Nonprecious Metal Catalysis

“…Unfortunately, only very electron-poor aryl chlorides appear to participate in the reaction, a common limitation of Cu catalysis. 50,51 Overall, the yields were moderate to good (typically with turnover numbers (TONs) of 3−8). This new class of cyclopentane- the added benefit of using a more convenient source of NH 3 than ammonia gas.…”

“…N , N ′-Bis­(3,5-dimethoxyphenyl)­cyclopentane1,1-dicarboxamide was identified as the optimal ligand, and the coupling was demonstrated for a range of aryl iodides and bromides using CuI (10 mol %), ligand (20 mol %), and Cs 2 CO 3 . Unfortunately, only very electron-poor aryl chlorides appear to participate in the reaction, a common limitation of Cu catalysis. , Overall, the yields were moderate to good (typically with turnover numbers (TONs) of 3–8). This new class of cyclopentane-1,1-dicarboxamide ligands offers promising activity for what is still a challenging reaction for Cu with the added benefit of using a more convenient source of NH 3 than ammonia gas.…”

Identification of an Oxalamide Ligand for Copper‐Catalyzed C−O Couplings from a Pharmaceutical Compound Library

“…The subsequent round of screening led to the identification of symmetrical oxalamide ligand 4 e as a promising lead. Further optimization of 4 e through rational design and structure‐activity studies led to the determination that the thiophene analogue 4 i was most effective for this coupling . Although oxalamides have been demonstrated to be viable ligands for a variety of Cu‐catalyzed transformations, these results highlight how the molecular diversity present in a pharmaceutical compound library can lead to the identification of functional ligand structures and inspire ligand design …”

“…of Cs 2 CO 3 were required for efficient conversion (entries 3-5). Copper salts were also tested and CuCl was deemed the most effective precursor (entries [6][7][8]. Polar aprotic solvents typically used in copper-catalyzed couplings did not outperform dioxane in the CÀ O coupling (entries 9-12).…”