Catalyst-Free Regioselective N² Arylation of 1,2,3-Triazoles Using Diaryl Iodonium Salts

Abstract

The widespread application of 1,2,3-triazoles in pharmaceuticals has resulted in substantial interest toward developing efficient postmodification methods. Whereas there are many postmodification methods available to obtain N 1 -substituted 1,2,3-triazoles, developing a selective and convenient protocol to synthesize N 2 -aryl-1,2,3-triazoles has been challenging. We report a catalyst-free and regioselective method to access N 2 -aryl-1,2,3-triazoles in good to excellent yields (66−97%). This scalable postmodification protocol is effective for a wide range of substrates.

Copper‐Catalyzed Selective N‐Arylation of Oxadiazolones by Diaryliodonium Salts

“…[24] The particular interest has been appealed by the N-arylation of heterocycles. The electron-rich heterocycles can be arylated by iodonium salts in relatively mild conditions, [37][38][39][40] while electron-poor (especially cyclic amides and related compounds) require the addition of catalyst. [41][42][43][44][45][46] Also, the synthetic procedures for preparing diaryliodonium salts make available the versatile scope of these compounds with high yields from common laboratory reagents.…”

“…The decrease of yield is in agreement with the behavior of sterically hindered diaryliodonium salt 2 f and reported data about arylation of Nnucleophiles with TMP-substituted iodonium salts. [37,39,42] To our delight, the reaction's scope could be extended to 1,3,4-oxadiazol-2(3H)-ones 5 (Scheme 6, a). The published approaches to arylation of 1,3,4oxadiazol-2(3H)-ones limited only to corresponding 5alkyl-derivatives prepared by interaction with haloar-Table 2.…”

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

“…As for metal-free approaches, besides synthesizing N-alkylated triazoles via 1,3-dipolar cycloaddition of alkyl azide with enols generated from carbonyl compounds under transition metal-free conditions [26], a direct functionalization of triazoles under metal-free conditions has been reported. These include the Broensted acid-catalysed N 2 alkylation [27], organocatalytic N 1 alkylation [28,29], N 2 -arylation using hypervalent iodine (Scheme 1c) [30], N 2 -alkylation involving radical intermediate [31], pyridine-N-oxide-mediated N 1 -arylation [32], NIS-mediated N 2 -arylation [33], etc. Although these are significant advances towards metal-free functionalization of triazoles, many of them suffer from poor regioselectivity.…”

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

“…In another approach, these N-alkylated triazoles can be prepared by using either direct alkylation of triazole under metal-free as well as transition metal catalyzed conditions [21,22]. Later, metal-free conditions were also developed to synthesize triazole derivatives, which included 1,3-dipolar cycloaddition of alkyl azide to enols generated from carbonyl compounds, N 2 -arylation using hypervalent iodine (Scheme 1c), N 2 -alkylation involving radical intermediate, pyridine-N-oxide mediated N 1 -arylation [23][24][25]. It is important to note here that the regioselective desulfonylative alkylation of N-tosyl-1,2-3-triazoles under metal-free and base-free conditions still remains unexplored.…”