2-Position-Selective C–H Perfluoroalkylation of Quinoline Derivatives

Abstract

We developed 2-position-selective, direct C-H trifluoromethylation, pentafluoroethylation, and heptafluoropropylation of quinoline derivatives. Regioselective transformation was achieved without derivatization of the quinolines. The reaction proceeded at room temperature with high functional group tolerance, even in gram scale. Notably, the reaction was applicable to substrates containing a functional group sensitive to oxidation and a drug molecule.

Transition‐Metal‐Free Direct Trifluoromethylation and Perfluoroalkylation of Imidazopyridines under Mild Conditions

“…Despite these advances, toxic metal catalysts, prerequisite directing groups or the high temperature may diminish the general application of such atom‐efficient C−H trifluoromethylation. To the best of our knowledge, transition‐metal‐free direct C−H trifluoromethylation of nonprefunctionalized heterocyles using TMSCF 3 as trifluoromethyl agent near room temperature is less reported ,. In addition, compared to trifluoromethylation, efficient and general methods for direct C−H perfluoroalkylation of nonprefunctionalized heterocyles with TMSC 2 F 5 or TMSC 3 F 7 are comparatively rare ,,,.…”

“…To the best of our knowledge, transition‐metal‐free direct C−H trifluoromethylation of nonprefunctionalized heterocyles using TMSCF 3 as trifluoromethyl agent near room temperature is less reported ,. In addition, compared to trifluoromethylation, efficient and general methods for direct C−H perfluoroalkylation of nonprefunctionalized heterocyles with TMSC 2 F 5 or TMSC 3 F 7 are comparatively rare ,,,. Thus, expanding the application of TMSC n F 2n+1 (n=1, 2, 3) in the fluorination of organic compound with higher atom‐efficient as well as getting the useful fluoroalkylated molecules is still challenging.…”

“…[2] Ruppert-Prakash reagent TMSCF 3 , a commercially available and relatively inexpensive material, has emerged as an efficient and economic reagent for the direct CÀH trifluoromethylation of arenes and heteroarenes. [3][4][5][6] Besides palladium, [3] copper [4] or silver-catalyzed [5] trifluoromethylation of arenes and heteroarenes with TMSCF 3 have been reported. Transitionmetal-free methods for the construction of CÀCF 3 bond have also been developed.…”

“…Transitionmetal-free methods for the construction of CÀCF 3 bond have also been developed. [6] Despite these advances, toxic metal catalysts, prerequisite directing groups or the high temperature may diminish the general application of such atom-efficient CÀH trifluoromethylation. To the best of our knowledge, transition-metal-free direct CÀH trifluoromethylation of nonprefunctionalized heterocyles using TMSCF 3 as trifluoromethyl agent near room temperature is less reported.…”

Synthetic Strategies, Reactivity and Applications of 1,5-Naphthyridines

“…In this way, 1,5-naphthyridine 56 was selectively trifluoromethylated at C-2 in 32% yield (compound 57 , Scheme 19 ). It is important to highlight that the reaction proceeded with high functional group tolerance, including an oxidation-sensitive formyl group, which might not be tolerated under the previous conditions [ 51 ].…”