Delivering 2-Aryl Benzoxazoles through Metal-Free and Redox-Neutral De-CF₃ Process

Abstract

An unexpected cleavage of the C sp3 –CF3 bond of CF3-hydrobenzoxazoles has been disclosed, affording a range of 2-aryl benzoxazoles under metal-free and redox-neutral conditions. This transformation has demonstrated broad substrate scope and good compatibility of functional groups. 2-Aryl benzothiazole and 2-aryl benzoimidazole could be smoothly assembled in the same manner. On the basis of preliminary mechanistic studies, base initiated and aromatization driven β-carbon elimination was considered to be the key step for the formation of 2. This reaction offers an alternative, facile, and sustainable route to access important 2-aryl benzoxazole motifs.

Theoretical Investigation of Ag(I) Acid-catalysed Cascade Benz Annulation of N-(3-(2-(4-Methoxybenzoyl)phenyl)prop-2-yn-1-yl)benzamide for Synthesis of Naphthooxazole

“…The naphtho [2,3-d]oxazole could be functionalized at C-2 position of substrates using transition-metal catalysts such as palladium-catalyzed direct cyclopropylation of heterocycles, copper-catalyzed visible light-induced C-H arylation of benzoxazoles, and light-promoted enantioselective alkylation of azoles [15][16][17]. Alternatively, the desired product could also be obtained by delivering 2-aryl benzoxazoles through metal-free and redox-neutral De-CF3 process [18]. To develop convenient construction of naphtho [2,3-d]oxazole analogues, challenges still exist in the invention of new synthetic methods utilizing versatile ortho-alkynylarylketone [19,20].…”

Reductive Cleavage of C(sp2)–CF3 Bonds in Trifluoromethylpyridines

“…The activation of the C–F bonds in trifluoromethyl groups can be achieved to prepare CF 2 R, CF 2 H, or CH 3 groups (Scheme B) . In contrast, the C–CF 3 bond is generally considered to be quite difficult to activate, and methods to cleave this linkage are rare. − Such defunctionalization reactions are important to the synthetic community, for example, to cleave directing/protecting groups or to remove halogens from persistent organic pollutants …”

“…Thiophene-bearing pyridine 3 was found to undergo detrifluoromethylation in a modest 37% yield. Other potentially reducible functional groups including a phenyl ether (4), thioether (5), trifluoromethyl ether (6), and chlorine (7) were tolerated, indicating that the reaction shows chemoselectivity for reduction of the trifluoromethyl C−C bond. A substrate bearing two trifluoromethyl groups was prepared and observed to undergo selective C−C cleavage at the pyridine 2-position ( 8), leaving the remote CF 3 group untouched.…”

Synthesis of Aryl-methylene Ethers through Pd(0)-Catalyzed Coupling between Hydrobenzoxazoles and Dichloromethane

“…However, to the best of our knowledge, Pd(0)-catalyzed cross-coupling reactions of DCM with possible nucleophiles through C–Cl bond cleavage have not yet been reported. We have previously reported a metal-free cleavage of the C–CF 3 bond of CF 3 -hydrobenzoxazoles, delivering a range of 2-aryl benzoxazoles . In principle, C–O bond cleavage in CF 3 -hydrobenzoxazoles is more facile than C–CF 3 bond cleavage.…”