Metal-free [3+2] cycloaddition of azides with Tf₂CCH₂for the regioselective preparation of elusive 4-(trifluoromethylsulfonyl)-1,2,3-triazoles

Abstract

1,2-Dipole Tf2CCH2 is generated in situ from 2-(2-fluoro-pyridin-1-ium-1-yl)-1,1-bis[(trifluoromethyl)-sulfonyl]ethan-1-ide and immediately reacted at room temperature with azides to afford previously unknown 4-trifluoromethanesulfonyl 1,2,3-triazoles in a highly regio- and chemoselective fashion.

Emerging approaches for the synthesis of triazoles: beyond metal-catalyzed and strain-promoted azide–alkyne cycloaddition

“…Despite being an elegant methodology for the one-pot synthesis of 1,4-disubstituted-1,2,3-triazoles, this protocol is limited by the low tolerability towards aryl azides containing electrondonating groups as well as benzyl azides. A similar reaction mechanism can be accounted for 4-triflic triazole formation described by Alcaide et al 30 A highly activated 1,2 Tf 2 C=C dipole is generated, which undergoes a stepwise (3+2)-cycloaddition, upon which the triazole formation can be finalized by the elimination of one triflate. On the other hand, Pathak demonstrated an intriguing methodology in which selective triazole substituent patterns could be obtained through the selection of the appropriate azide (Scheme 15).…”

Synthesis of heteroarenes dyads from heteroarenes and heteroarylsulfonyl chlorides via Pd-catalyzed desulfitative C–H bond heteroarylations

“…The reaction performed with benzofuran as the starting 35 material led to the unexpected debrominated coupling product 5 in 42% yield. Interestingly, the reaction conditions tolerates enolizable ketone substituent as 1-(furan-2yl)propan-2-one reacted with 4-bromo-2,5-dichlorothiophene-3sulfonyl chloride to provide the desired arylated product 4 in 65% yield.…”

“…Then, the base assisted the rearomatization process gives the intermediates D and F, which undergo reductive elimination to afford the desired 35 arylated products and regenerates the Pd(II) catalysts. Then, the base assisted the rearomatization process gives the intermediates D and F, which undergo reductive elimination to afford the desired 35 arylated products and regenerates the Pd(II) catalysts.…”

“…For examples, RITA an heteroaryl triads containing a furan 2,5substituted by thiophenes, is a potent multi-target drug against 20 cancer. 4 Palladium catalysis is 35 a very useful tool for the C-C bond formation. 2 Benzofuranyl-pyrrole derivative I act as potent retinoic acid receptor α agonist.…”

Synthesis and Characterization of Stable Phosphorus Carbabetaines

“…[11] Recently,w efound that 2-fluoropyridinium salt 3 was an effective reagent for the in situ generation of highly electrophilic1 ,1-bis(trifluoromethylsulfonyl)ethylene (4;S cheme1)a nd was successfully appliedt ot he synthesis of as uperacidic carbon acid, denoteda sT f 2 CHR. [12] Cycloaddition reactions of in-situ-generated compound 4 with 1,3-dienes, [12b, 13] alkynes, [14] and organica zides [15] also proceeded smoothly to produce the corresponding triflones. Although 2-fluoropyridinium salt 3 rapidly formed an equilibrium mixture of compound 4 and 2-fluoropyridine in MeCN, the reagent itself is as helf-stable and easy-to-handle crystalline solid.…”