Science of Synthesis

Harris, T.; Alabugin, I. V., Science of Synthesis: Click Chemistry, (2021) 1, 337.

The cycloalkyne (dipolarophile) and azide (1,3-dipole) react through a Huisgen 1,3-dipolar cycloaddition,[‌33‌–‌36‌] a process where the two unsaturated components form a new cycloadduct by converting π-bonds into σ-bonds (‌Scheme 1‌).[‌37‌,‌38‌] The 1,3-dipolar cycloaddition is a pericyclic reaction where bond formation and breaking between the cycloalkyne and azide occur simultaneously via a cyclic transition state.[‌39‌–‌41‌] Similar to other pericyclic reactions, the transition state is aromatic and stabilized by symmetry-enforced cyclic delocalization.[‌42‌] For an example of a cyclic aromatic transition state in a non-pericyclic reaction see ref[‌43‌]. Alternative stepwise, diradical or zwitterionic mechanisms for the 1,3-dipolar cycloaddition have been proposed.[‌44‌,‌45‌] However, if some diradical or zwitterionic character is present, the transition state is still concerted but asynchronous.[‌46‌–‌49‌] Because SPAAC processes are generally highly exergonic, they proceed via relatively early, asynchronous transition states.

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References