Cycloadditions with Strained or Activated Alkynes

Typically, organic azides and terminal alkynes do not react together (within the context of a click reaction) at ambient temperature and in the absence of a transition-metal catalyst. 

Atypically however, alkynes may be activated by alternative strategies that eschew the use of a catalyst altogether. The manners in which activation may be achieved have been either the application of ring strain to an alkyne, the incorporation of an EWG or a combination of both. 

The azide-DIFO cycloadditions therefore present a mild and fast conjugation methodology perfectly suited to biochemical applications such as in vivo dynamic imaging of cell-surface glycans in live cells. However, the laborious synthetic pathway of the precursor DIFO derivatives still stands in the way of such a system to be more widely investigated and, as of yet, the technique has not been applied to the design and construction of synthetic materials. 

Accelerating the rate of reaction such that it may be completed within 2h, Gouin and Kovensky reported a further electron-deficient alkyne (p-toluene sulfonyl alkyne) as shown in 

In perhaps the most elegant example to date of the use of thiol-ene chemistry for macromolecular synthesis. Hawker and colleagues prepared up to fourth-generation dendrimers 

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