The Development of Copper‐Catalyzed Aerobic Oxidative Coupling of H‐Tetrazoles with Boronic Acids and an Insight into the Reaction Mechanism

Abstract

The development of a highly efficient and practical protocol for the direct C-N coupling of H-tetrazole and boronic acid was presented. A careful and patient optimization of a variety of reaction parameters revealed that this conventionally challenge reaction could indeed proceed efficiently in a very simple system, that is, just by stirring the tetrazoles and boronic acids under oxygen in the presence of different Cu(I) or Cu(II) salts with only 5 mol % loading in DMSO at 100 °C. Most significantly, the reaction could proceed very smoothly in a regiospecific manner to afford the 2,5-disubstituted tetrazoles in high to excellent yields. A mechanistic study revealed that both tetrazole and DMSO are crucial for the generation of catalytically active copper species in the reaction process in addition to their role as reactant and solvent, respectively. It is demonstrated that in the reaction cycle, the Cu(I) catalyst could be oxidized to Cu(II) by oxygen to form a [CuT2D] complex (T = tetrazole anion; D = DMSO) through an oxidative copper amination reaction. The Cu(II) complex thus formed was confirmed to be the real catalytically active copper species. Namely, the Cu(II) complex disproportionates to aryl Cu(III) and Cu(I) in the presence of boronic acid. Facile elimination of the Cu(III) species delivers the C-N-coupled product. The results presented herein not only provide a reliable and efficient protocol for the synthesis of 2,5-disubstituted tetrazoles, but most importantly, the mechanistic results would have broad implications for the de novo design and development of new methods for Cu-catalyzed coupling reactions.

Copper tetrazolate based metal‐organic frameworks as highly efficient catalysts for artificially chemical and electrochemical CO2 conversion

“…[ 8a ] And the disappearance of the ligand NH signals (2500−3300 cm −1 ) in the FT‐IR spectra further demonstrate the coordination of N to Cu of Cu−5H, Cu−5M, and Cu−5P, which is also verified by the observation of Cu−N peak at 500−800 cm −1 in their Raman spectra (Figure S1). [ 7d,9 ] The intensive peaks around 5 o to 20 o in the XRD patterns (Figure 1B), which is similar with the reported literatures, [ 8,10 ] further prove the successful formation of Cu tetrazole MOFs as well as their excellent crystallinity. According to the previous reports, [ 8,10 ] it is proposed that Cu−5P is formed with the common unit of Cu(5P) 2 DMSO (DMSO: dimethyl sulfoxide), wherein Cu(II) center connects with two tetrazole anions via Cu−N bond and one DMSO molecule.…”

“…[ 7d,9 ] The intensive peaks around 5 o to 20 o in the XRD patterns (Figure 1B), which is similar with the reported literatures, [ 8,10 ] further prove the successful formation of Cu tetrazole MOFs as well as their excellent crystallinity. According to the previous reports, [ 8,10 ] it is proposed that Cu−5P is formed with the common unit of Cu(5P) 2 DMSO (DMSO: dimethyl sulfoxide), wherein Cu(II) center connects with two tetrazole anions via Cu−N bond and one DMSO molecule. And Cu−5M is Cu(5M) 2 DMSO while Cu−5H is Cu(5H) 2 DMSO.…”

Newly Developed CK1-Specific Inhibitors Show Specifically Stronger Effects on CK1 Mutants and Colon Cancer Cell Lines

“…In order to identify IWP-based inhibitor compounds stronger inhibiting CK1δ mutants than CK1δ WT , new compounds were designed based on the IWP backbone structure. Chan-Lam coupling of compounds 1−4 was performed based on the literature (Scheme 1) [25]. Instead of using an oxygen filled balloon, compressed air was passed through the solvent.…”

Copper‐Catalyzed Regioselective Oxidative Cycloamidation of α‐[(β‐Dimethylamino)propenoyl]‐Alkylamides: Synthetic Route to Substituted Pyrrolidine‐2,4‐diones

“…To get further information, the reaction of 1 a and PIFA was conducted in the presence of TFA and CuBr 2 under argon atmosphere, and the precipitates recovered from the reaction mixture at different reaction time were investigated by means of X‐ray photoelectron spectroscopy (XPS). As illustrated in Figure , the black residue recovered at the initial reaction stage showed characteristic signals at 931.6 and 933.1, which could be easily assigned to the 2p 3/2 binding energies of Cu I and Cu II , respectively . In contrast, the signal at 933.1 disappeared for the off‐white residue recovered at the final reaction stage.…”