Copper(I)-Catalyzed Synthesis of Azoles. DFT Study Predicts Unprecedented Reactivity and Intermediates

Abstract

Huisgen's 1,3-dipolar cycloadditions become nonconcerted when copper(I) acetylides react with azides and nitrile oxides, providing ready access to 1,4-disubstituted 1,2,3-triazoles and 3,4-disubstituted isoxazoles, respectively. The process is highly reliable and exhibits an unusually wide scope with respect to both components. Computational studies revealed a stepwise mechanism involving unprecedented metallacycle intermediates, which appear to be common for a variety of dipoles.

Metal-catalyzed azide-alkyne “click” reactions: Mechanistic overview and recent trends

“…Since the early reports, a variety of transition-metal catalysts have been used for the reactions between mono-or disubstituted alkynes and azides (vide infra). For the Cu(I) catalyzed reaction, a variety of mechanisms involving Cu(I)-aryl intermediates have been proposed in which the key-step species contains either mononuclear [35] or binuclear copper species [30][31][32][33][34][35][36][37][38]. Theoretical studies of the RuAAC reaction have also been reported [28,[39][40][41].…”

Modern Synthetic Avenues for the Preparation of Functional Fluorophores

“…Cycloaddition reactions are a valuable strategy to access highly functionalized structures owing to their experimental ease, good synthetic yields, and compatibility with multiple functional groups,38 with the alkyne–azide 1,3‐dipolar Huisgen cycloaddition39 being one of the most widely used reactions in chemical biology. This strategy was utilized by Fairfull‐Smith and co‐workers to conjugate azidocoumarin derivatives to an alkyne‐containing isoindoline nitroxyl in a copper‐catalyzed azide–alkyne cycloaddition (CuAAC) process to generate fluorophores with high sensitivity to oxidative processes (Figure 6 A) 40.…”

Sulfonyl and Phosphoryl Azides: Going Further Beyond the Click Realm of Alkyl and Aryl Azides

“…The corresponding formation of a N-alkyl-or aryltriazolyl copper species has been previously investigated. [15] Although the involvement of more than one copper might be possible, a mononuclear copper acetylide with one pyridine spectator ligand on copper was chosen as a starting point as our interest is in comparing the reactivity of N-sulfonyl azide to Nalkyl analogues (X1, Figure 3). For methanesulfonyl azide (X4) used in this study, the overall barrier for the formation of metallacycle (X3ts) was calculated at 57 kJ mol À1 .…”