Cycloaddition Reactions with Azides: An Overview

Synthesis of N-unsubstituted 1,2,3-triazoles via a cascade including propargyl azides, allenyl azides, and triazafulvenes

“…In the case of very volatile nucleophiles like ammonia, methylamine, or dimethylamine, the second step has to be performed in an autoclave to avoid early loss of NuH. Alternatively, lower temperatures (50-60 °C) and longer reaction times can be used (entries [11][12][13]. When heated in the presence of organic azides, unsaturated compounds, such as allyl and propargyl alcohols, can undergo unwanted 1,3-dipolar cycloaddition to generate disubstituted 1H-1,2,3-triazoles.…”

“…The methanol was evaporated and the residue contained a mixture of 5cc (69−71%), and cinnamonitrile (10, 9%), analyses by 1 H NMR including an internal standard. (11). Sodium azide (6.5 g, 0.1 mol) was dissolved in water (80 mL); 3-bromo-1-propyne (1a, 8.3 mL, 0.11 mol) in ethylene glycol dimethyl ether (400 mL) was added, and the mixture was stirred at 22 °C for 18 h. The reaction mixture was charged with 2-chloroethanol (1.0 L, 14.93 mol) and heated to 65−70 °C for 3 h. The volatiles were removed under reduced pressure.…”

“…[6][7] This regioselective formation of 1,4-disubstituted 1H-1,2,3-triazoles has proved to be the best example of click chemistry 8 and has found extensive applications in manifold domains of chemistry. [9][10][11] However, N-unsubstituted, so-called NH-1,2,3-triazoles, cannot be prepared directly by means of a copper-catalyzed [3+2]-cycloaddition strategy. Thus, their synthesis requires special azides and a sequence involving cycloaddition and deprotection steps.…”

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

“…[4][5] This copper-catalyzed azide alkyne cycloaddition (CuAAC) has since found widespread use even outside the chemistry community. [6][7][8][9][10][11] However, a method to form the corresponding 1,5-disubstituted 1,2,3-triazole isomer was also needed. In 2005 this problem was solved by Fokin and Jia,12 who showed that by exchanging copper for ruthenium, this class of isomers could also be accessed.…”

Convenient Room‐Temperature, Mercury‐Assisted Synthesis of Tetrazoles by 1,3‐Dipolar Cycloaddition

“…[14,15] It is reported that the reaction of various organic azides with various nitriles failed with nitriles that were not activated, even with the use of various catalysts.…”