Base-Induced Highly Regioselective Synthesis of N²-Substituted 1,2,3-Triazoles under Mild Conditions in Air

Abstract

We developed a highly regioselective base-induced synthesis of N 2-substituted 1,2,3-triazoles from N-sulfonyl-1,2,3-triazoles and alkyl bromides/alkyl iodides at room temperature. We propose an SN2-like mechanistic pathway to explain the high N 2-regioselectivity. The protocol features a broad substrate scope and generates products in good to excellent yields (72–90%).

Borinic Acid Catalyzed Regioselective N-Alkylation of Azoles

“…Methods for regioselective functionalization of azoles have attracted significant interest, particularly in medicinal chemistry, where applications of such heterocycles are extensive and diverse. − A range of approaches have been developed to address the challenge of ambident reactivity , in the N -functionalization reactions of pyrazoles, 1,2,3-triazoles, 1,2,4-triazoles, tetrazoles, purines, and related heterocycles . Versatile methods that enable selective functionalization of several heterocycle classes, including enantioselective, catalytic transformations, have also been reported.…”

Iodine-catalyzed intermolecular 1,2-thio (seleno)amination of alkenes with 1,2,3-triazoles and disulfides (diselenides) in air

“…9 The classic reaction pathways of N -sulfonyl-1,2,3-triazoles are processed via active intermediates, including carbenes generated with heating or a metal catalyst with subsequent cyclopropanation, 10 C–H insertion, 11 N–H insertion, 12 ring expansion, 13 rearrangement 14 or C–H functionalization. 15 N -sulfonyl-1,2,3-triazoles can also serve as nucleophilic reagents and subsequently undergo nucleophilic addition 16 or substitution 17 to afford a series of different substituted triazoles. Very recently, we found an effective C(sp 3 )–H oxidative radical coupling reaction of tetrafuran with N -sulfonyl-1,2,3-triazoles in which triazole radicals were generated in situ via a synergetic desulfonation and were involved in this reaction.…”

Copper-Catalyzed Intermolecular 1,2-Carbotriazolization of Alkenes with N-Sulfonyl-1,2,3-Triazoles and Aldehydes

“…N -Sulfonyl-1,2,3-triazoles are an important class of synthetic heterocycles and receive considerable attention in synthetic and medicinal communities because of their widespread application as building blocks and pharmacophores . The classic reaction pathways of N -sulfonyl-1,2,3-triazoles were processed via cyclopropanation, C–H insertion, O–H insertion, ring expansion, rearrangement, hydrolysis, and N-substitution reaction. , Therefore, we envisioned developing a three-component radical 1,2-carbotriazolization reaction using 1,2,3-triazoles to trap a carbon-centered relay radical ( 1i ) or a carbocation ( 1ii ). The commonly used alkyl radical precursors ( 1 , such as alkyl halide, alkyl nitriles), styrene ( 2 ), and N H-1,2,3-triazole ( 5 ) were first used to test the desired reaction, but no products were observed as expected (see Scheme S4).…”