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

Abstract

Triazole derivatives R 0280Copper(I)-Catalyzed Synthesis of Azoles. DFT Study Predicts Unprecedented Reactivity and Intermediates. -Cu-catalyzed addition of azides or nitrile oxides to acetylenes offers an efficient, widely applicable and regiospecific approach to 1,4-disubstituted 1,2,3-triazoles and 3,5-disubstituted isoxazoles, respectively. A stepwise mechanism is revealed which involves unprecedented metallacycle intermediates. -(HIMO, F.; LOVELL, T.; HILGRAF, R.; ROSTOVTSEV, V. V.; NOODLEMAN*, L.; SHARPLESS, K. B.; FOKIN, V. V.; J.

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

“…The reactivity of internal alkynes is also an indication that the reaction does not proceed via a ruthenium acetylenide, in contrast to the CuAAC reaction that involves an intermediate copper acetylenide. 53 Mechanistic proposals for this reaction are summarized in the next chapter.…”

“…53 The reaction without any catalyst has a rather high barrier for both 1,4-and 1,5-regioisomers, with a relative energy of 25.7 and 26.0 kcal/mol respectively. Both reaction pathways were reported to be highly exothermic with over 60 kcal/mol, not accounting for entropy effects.…”

Selective chemical protein modification

“…The absence and reasonable inertness of azides and alkynes in biology has made the copper-catalysed azide-alkyne 'cycloaddition' (CuAAC) an excellent candidate for undertaking modification of biomolecules (although it should be noted that the CuAAC is not a true cycloaddition, rather proceeding via a metallocyclic intermediate 74 ). In early demonstrations, Wang et al 75 coated cowpea mosaic virus with azide or alkyne moieties via nonspecific lysine labelling and then undertook CuAAC reactions to fluorescently label the capsid.…”

Click Chemistry, A Powerful Tool for Pharmaceutical Sciences

“…It typically does not require temperature elevation but can be performed over a wide range of temperatures (0-160°C), in a variety of solvents (including water), and over a wide range of pH values (5 through 12). It proceeds as much as 10 7 times faster than the uncatalyzed version, and purification essentially consists of product filtration (3,(5)(6)(7). Furthermore, it is unaffected by steric factors.…”