A Simple Phosphine–Diolefin‐Promoted Copper‐Catalysed N‐Arylation of Pyrazoles with (Hetero)aromatic Bromides: The Case of Chloroarenes Revisited

Abstract

A molecularly defined new phosphine–diolefin cubane copper pre‐catalyst used at 1.25 mol % under mild conditions promotes the coupling of pyrazoles to functionalised aryl and heteroaryl bromides, which hold a variety of functional groups. This versatile phosphorus‐based system was thus successfully used, under identical conditions, for the coupling of a large scope of heteroaromatics to selectively produce pyridinyl‐ and pyrimidinyl‐pyrazoles, as well as several novel furyl‐, thienyl‐ and thiazolyl‐substituted pyrazoles. The careful investigation of coupling with the analogous aryl and heteroaryl chlorides clearly indicated that for specifically activated chloroarenes a direct nucleophilic aromatic substitution (SNAr) is easily achieved in the absence of any copper and ligand. These results are pertinent with regards to the reported protocols in which copper–ligand systems have been claimed as useful for coupling activated chloroarenes.

Palladium‐Catalysed CH Bond Electrophilic Fluorination of Highly Substituted Arylpyrazoles: Experimental and DFT Mechanistic Insights

“…Arylpyrazoles are easily made by CN bond formation (Scheme ) 14. We reasoned that a pyrazole unit might be an efficient directing group for CH bond fluorination as it has been nicely demonstrated for CC bond formation by the introduction of phenyl and nitrile groups 11,15,16.…”

“…All reactions were performed in Schlenk tubes under argon. Unless otherwise stated, the starting pyrazole derivatives were synthesised according to the literature 14 . 1 H (300 MHz), 13 C (75 or 125 MHz), 19 F (282 or 470 MHz) spectra were recorded on Bruker AVANCE III instrument in CDCl 3 solutions.…”

The Structure ofN‐phenyl‐pyrazoles and Indazoles: Mononitro, Dinitro, and Trinitro Derivatives

“…For the second one, compound 36 : microwave irradiation ; Cu(I) catalysts: copper‐anchored porous zinc‐based metal–organic framework heterogeneous conditions , sulfonic acid‐based cation‐exchanger resin “INDION 770” , 8‐hydroxyquinoline‐ N ‐oxide ligand for CuBr , 10 mol% of CuI as catalyst and 1.2 equivalent NaH as base , CuI in ionic liquid [Bmim]BF 4 as a reaction medium , phosphine‐diolefin cubane copper pre‐catalyst , Salen‐Cu(II) complex , activated‐copper powder in water with LiOH as base , copper(I) 3‐methylsalicylate , 3‐(diphenylphosphino)propanoic acid an efficient ligand for Cu‐catalysts , metal–organic framework [Cu(INA) 2 ] as heterogeneous catalyst , surfactant/copper‐based ionic liquid/water , and for a general discussion about the frontier between nucleophilic aromatic substitution and catalysis, see ; the use of t‐BuOK or K 2 CO 3 in dimethyl sulfoxide has been updated .…”

In Silico and Biological Evaluation of N‐(2‐methoxyphenyl) Substituted Pyrazoles Accessed via a Sonochemical Method

“…Accordingly, CuI‐catalyzed N ‐arylation of various nitrogen containing heterocycles including pyrazoles with aryl and heteroaryl halides have been reported (Method B, Scheme 1). [21–24] …”