Mild, rapid and efficient metal-free synthesis of 2-aryl-4-aryloxyquinolines via direct Csp2O bond formation by using diaryliodonium salts. Issue 4 (25th January 2017)

• Record Type: Journal Article
• Authors: Nahide, Pradip D.; Solorio-Alvarado, César R.
• Is Part Of: Tetrahedron letters. Volume 58:Issue 4(2017)
• Page Start: 279
• Page End: 284
• Publication Date: 2017-01-25
• Subjects: 2-Aryl-4-aryloxyquinolines -- Iodonium salts -- Direct Csp2O bond formation -- Ligand- and metal-free reactions -- Non-toxic reactions; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.11.093
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: The first general method for synthesizing in one-pot the pharmacophore 2-aryl-4-aryloxyquinolines. A metal- and ligand-free procedure for the formation of a CO bond yielding functionalized quinolines. A totally, regio- and chemoselective O -arylation procedure for the functionalization of quinolines. The use of non symmetrical bisaryliodonium salts expending only PhI as organic byproduct. Abstract: An efficient ligand- and transition metal-free procedure for the direct Csp 2 O bond formation for the arylation of 2-aryl-4-quinolones was developed. The synthesis of the starting quinolones was carried out under our optimized Cu-catalyzed CN bond formation conditions between 2′-bromoacetophenone and benzamide derivatives followed by cyclization. Easily prepared diaryliodonium salts were used as aryl source. Highly functionalized 4-aryloxyquinolines were obtained in a mild and operationally simple protocol, which involves conventional heating and short periods of time. The method shows good to excellent yields and broad toleration of functional groups like fluorine or trifluoromethyl, which are important in medicinal chemistry. The Csp 2 O bond formation process herein described for the quinolone functionalization offers an excellent non-toxic alternative to the transition metal-catalyzed reactions that not only can potentially contaminate the final compounds but also can be environmental pollutants.