Year: 2026
Type: preprint
Abstract: The Cu I -triazolide intermediate of the Cu-mediated alkyne-azide cycloaddition (CuAAC) typically undergoes rapid proto-demetallation but can be intercepted by suitable coupling partners to give 5-substituted triazole products. However, the scope of such “interrupted click” reactions is restricted because some partners react too slowly to outcompete proto-demetallation or even actively promote the decomposition of the Cu I -triazolide in preference to the desired coupling. Here we show that mechanical stabilisation of a Cu I -triazolide within a [2]rotaxane can allow otherwise unproductive “hidden” interrupted click reactions to proceed; the triazolide intermediate of the active template CuAAC reaction couples with cyanide and primary amines under oxidative conditions to install these groups at the triazole 5-position in up to 99% yield. In contrast, the interlocked triazolide reacts slowly with some typical interrupted electrophiles that intercept non-interlocked Cu I -triazolides. Based on these reactivity trends, we propose that the mechanical bond prevents direct attack of electrophiles on the Cu-C bond, instead enforcing inner-sphere reactivity at the Cu I centre with a Cu I /Cu III /Cu I redox cycle. The C-5 substituent leads to a new source of mechanical positional isomerism and a suitably designed macrocycle can be removed after the coupling, allowing the interlocked architecture to serve as an auxiliary for products of otherwise inaccessible interrupted click reactions.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7221613317