Cycloaddition reactions copper-free click chemistry

For an example of such interaction in the TS of non-catalyzed alkyne/azide cycloaddition (click reaction), see Gold, B., Shevchenko, N. E., Bonus, N., Dudley, G. B., Alabugin, 1. V. (2012). Selective Transition State Stabihzation via Hyperconjugative and Conjugative Assistance Stereoelectronic Concept for Copper-Free Click Chemistry. The Journal of Organic Chemistry, 77(1), 75-89. 

The [3+2] cycloaddition reaction of azides with terminal olefins is of considerable interest in the modification of biomolecules, because the azide group is abiotic in animals. Especially, the Cu(i) catalyzed cycloaddition reaction of azides with terminal alkynes achieves regioselective formation of 1,4-disubstituted 1,2,3-triazoles and this reaction is currently referred to as click chemistry . In the thermal reaction of azides with terminal alkynes, about 1 1 mixtures of 1,4- and 1,5-disubstituted 1,2,3-triazoles are obtained. Likewise, disubstituted alkynes afford mixtures of the stereoisomers. In order to avoid the cellular toxicity caused by the copper catalyst, Cu-free click chemistry is of considerable interest. The use of strained cyclooctyne derivatives as dipolarophiles was proposed recently. In this manner a novel 6,7-dimethoxyazacyclooct-4-yne was constructed from a glucose analogue s. The disadvantage of this reaction is its significantly slower reaction rate but introduction of fluoro groups adjacent to the triple bond achieves some rate enhancement. ... 

---