Metal‐Free Synthesis of Functional 1‐Substituted‐1,2,3‐Triazoles from Ethenesulfonyl Fluoride and Organic Azides

Abstract

The boom in growth of 1,4‐disubstituted triazole products, in particular, since the early 2000’s, can be largely attributed to the birth of click chemistry and the discovery of the CuI‐catalyzed azide–alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1‐substituted‐1,2,3‐triazoles has been surprisingly more challenging. Reported here is a straightforward and scalable click‐inspired protocol for the synthesis of 1‐substituted‐1,2,3‐triazoles from organic azides and the bench stable acetylene surrogate ethenesulfonyl fluoride (ESF). The new transformation tolerates a wide selection of substrates and proceeds smoothly under metal‐free conditions to give the products in excellent yield. Under controlled acidic conditions, the 1‐substituted‐1,2,3‐triazole products undergo a Michael addition reaction with a second equivalent of ESF to give the unprecedented 1‐substituted triazolium sulfonyl fluoride salts.

Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluoride (SASF) Hubs

“…Other reactions have since joined the ranks of the click family; each with roots in the “old‐school” literature, including thiol–ene click chemistry—finding wide application in polymer and materials science; Sulfur‐Fluoride Exchange (SuFEx)—a prime method for a wealth of applications, and a powerful diazotransfer agent (diazo‐click) for the guaranteed azidation of primary amines (Figure A) . While these incredibly reliable transformations (Figure ) have become the go‐to click reactions, with few exceptions, the development of the wider family of selective “spring‐loaded” click‐like processes identified in the click chemistry manifesto have been somewhat overlooked (Figure A).…”

Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluoride (SASF) Hubs

“…Other reactions have since joined the ranks of the click family; each with roots in the "old-school" literature, including thiol-ene click chemistry-finding wide application in polymer and materials science; [25,26] Sulfur-Fluoride Exchange (SuFEx)-a prime method for a wealth of applications, [27][28][29][30][31][32][33][34][35][36][37][38][39] and a powerful diazotransfer agent (diazo-click) for the guaranteed azidation of primary amines (Figure 1 A). [40] While these incredibly reliable transformations ( Figure 1) have become the go-to click reactions, with few exceptions, [26,41] the development of the wider family of selective "spring-loaded" click-like processes identified in the click chemistry manifesto have been somewhat overlooked (Figure 1 A).…”

A Photoinduced Multicomponent Regioselective Synthesis of 1,4,5‐Trisubstituted‐1,2,3‐Triazoles: Transition Metal‐, Azide‐ and Oxidant‐Free Protocol

“…[25] However, most reactions reported so far depend on organic azides that are explosive and hard to handle on a large scale. [26] A noteworthy transition metal-and azide-free protocol for the synthesis of triazoles has been explored by multicomponent and oxidative coupling reactions. [27,28] Therefore, more attention has been gained towards the design of transition metal-and azide-free routes for the synthesis of 1,2,3-triazoles from readily available and cheap starting materials.…”

“…In order to overcome these, Ramachary, Bressy and Wang have developed metal‐free enamine or enolate based organocatalytic azide‐ketone [3+2] cycloaddition reaction, which now prospers as Ramachary‐Bressy‐Wang's [3+2] cycloaddition [25] . However, most reactions reported so far depend on organic azides that are explosive and hard to handle on a large scale [26] . A noteworthy transition metal‐ and azide‐free protocol for the synthesis of triazoles has been explored by multicomponent and oxidative coupling reactions [27,28] .…”