Mechanistic Studies of Ullmann‐Type C–N Coupling Reactions: Carbonate‐Ligated Copper(III) Intermediates

Abstract

In Ullmann‐type C−N coupling reactions, the involvement of CuIII species has been proposed many times on the basis of the oxidative addition–reductive elimination (OA‐RE) path for these reactions, but actual species could not be traced in experimental studies. In the C−N coupling reactions, carbonate and phosphate were considered widely as bases. In the present study, Cu‐mediated C−N coupling reactions of aryl halides and NuNH (amide and imide) were investigated extensively, and we provide direct spectroscopic evidence of actual CuIII species. For the first time, we reveal that carbonate and phosphate ions act as bidentate ligands as well as a base in the catalytic cycle, and thus the actual intermediate species is a carbonate‐ or phosphate‐ligated, distorted octahedral CuIII complex. Our experimental and computational studies have strengthened the hypothesis that these reactions follow an OA‐RE path.

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

“…For the formation of 14, L1Cu + (1) is selected as initial species, it reacts with AcNH2 and CO3 2-and can turn in to 14 and 6 respectively (Scheme-III It has good agrrement with our previous studies [12]. Recentlly, it is also reported that deactivaation of catalyst is more significant in fine powdered K2CO3 [15].…”

“…It was proposed that benzene forms through trapping of hydrogen from solvent or ligand by phenyl free radical. Cu(II) species can form through free aryl radical formation via outer sphere electron transfer ( ever, these reactions operate through oxidative addition-reductive elimination pathway [12,21]. Calculated free energy barriers for free radical formation are very high (93 kcal/mol).…”

“…It has been reported that higher loading of metal salt or more equivalents of ligand are required to sustain it in active form. Higher concentration of base also has adverse effect on catalytic activity [12][13][14]. Efforts have been made to find out reason of deactivation of catalyst but it could not be well understood [15].…”

Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 1,2,3-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design, Synthesis, and Biological Evaluation

“…In this case, applying our knowledge of the Arrhenius equation, in which the energy transmitted by microwaves affects the parameters of pressure, heating and especially time. The reaction time in all C-N couplings could be reduced for the synthesis of anilines when we increase the temperature to 160 • C [76][77][78].…”

Cost Efficient Synthesis of Diaryl Ethers Catalysed by CuI, Imidazolium Chloride and Cs2CO3

“…In this report, we have utilized UV‐Vis, FT‐IR and HRMS techniques to investigate the catalytic process. The UV‐Vis absorption spectrum of the phenol and iodobenzene were monitored separately with successive addition of catalytic substances such as CuI, Cs 2 CO 3 , L1 and finally the second substrate iodobenzene (PhI) to phenol (PhOH) and vice‐versa . The addition of CuI, Cs 2 CO 3 and L1 to the PhOH produced a shoulder around 240 nm in the phenol UV‐Vis absorption spectrum (Figure , (A)), whereas in the case of iodobenzene significant changes were not observed for similar additions (Figure , (B)).…”