DMSO is a colorless and transparent liquid at room temperature, with a high melting point (18.45 ℃) and a high boiling point (189 ℃). DMSO is miscible with water and most common organic solvents. DMSO can dissolve many organic and inorganic compounds well and has low toxicity, so it is widely used in both academic and industrial circles.
Transition metal-catalyzed cross-coupling reactions of aryl halide electrophiles and heteroatom nucleophiles are widely used in the construction of pharmaceutical molecules, agrochemicals, and functional materials. Recently, researchers have reported some divalent anion-bonded ligands to generate catalysts that can achieve challenging cross-coupling reactions. In particular, oxamide ligand-copper catalysts are more active than previous copper catalysts, but currently the mechanistic explanation for its high activity has not yet been reported.
Recently, some researchers have discovered that the Ullmann coupling reaction catalyzed by Cu(II) complexes complexed with oxamide ligands proceeds through the cooperative oxidative addition of aryl halides and Cu(II) to form high-valent copper species in DMSO.
Computational studies show that this high-valent species can be stabilized by radical features on the oxamide ligand. Undoubtedly, this mechanism is significantly different from those involving Cu(I) and Cu(III) intermediates, which have been used in other Ullmann-type coupling reactions.
1-Bromo-4-fluorobenzene and potassium phenolate reacted at 100 °C for 16 h under the conditions of CuI as the catalyst, H2-BPPO as the ligand, and DMSO as the solvent. The coupling product could be formed with a yield of 98%. And through multiple experiments, it has been shown that Cu(I) species is not an intermediate in the catalytic process.
In order to explore the Cu(II) complex in the catalytic reaction, the researchers heated aryl halides, phenolates, copper iodide and oxalamide at 100 °C for 20 min in DMSO as the solvent. The EPR spectrum of the reaction mixture can correspond to a Cu(II) species. In addition, the Cu(II)-dioxalamide complex bonded by four nitrogen atoms is the most reasonable structure that matches the EPR data of the catalytic reaction. It can be independently synthesized from CuBr2, ligands and bases and has been fully characterized.
Since Cu(II) complexes can initiate reactions catalyzed by the Cu(I)/Cu(III) pair, the researchers further explored whether the Cu(II) complexes were real catalysts or precatalysts that were reduced to Cu(I). . The results show that the disproportionation of two equivalents of Cu(II) complexes into Cu(I) species and the corresponding Cu(III) species is reversible, thus excluding the disproportionation of Cu(II) species to generate Cu(I) active species.
To evaluate whether copper-phenolate complexes react with aryl halides, the researchers performed kinetic studies, which showed that the electrical properties of the phenolate had no effect on the reaction rate, suggesting that the phenolate does not bind to copper in the turnover-limiting step. , and also excludes the σ-bond metathesis mechanism. Secondly, the irreversible combination of aryl halides before the SNAr reaction of phenolate was excluded experimentally. The researchers also conducted free radical capture experiments, but the results showed that no cyclization products were formed when phenolates and aryl halides reacted, thus ruling out the free radical oxidative addition mechanism. Taken together, all results are consistent with a cooperative redox mechanism.
Finally, the researchers also used density functional theory (DFT) calculations to evaluate the mechanism by which Cu(II) species reacts with aryl halides to cleave C-X bonds.
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Reference
- Cross-coupling by a noncanonical mechanism involving the addition of aryl halide to Cu(II)
Science, 2023, 381, 1079-1085
