Science of Synthesis

Svatunek, D.; Houk, K. N., Science of Synthesis: Click Chemistry, (2021) 1, 430.

While click chemistry is certainly dominated by Diels–Alder reactions and cycloadditions between azides and alkynes, the field of 1,3-dipolar cycloadditions of alkenes is a promising one and has seen rapid growth in the past years. Building upon chemistry that was first described decades, or even over a century, ago by chemists such as Huisgen, Alder, Franz, and Pechmann, these cycloadditions have been brought back to serve a new purpose. The instability of the reaction product that is formed from the highly popular azides and alkenes hampered the development and popularity of this class of reactions. However, creative chemists have found ways to work around this instability, as demonstrated by the work of Rutjes[‌28‌] and Vrabel.[18] The instability was used to develop “click to release” chemistry, as demonstrated by Gamble.[‌19‌] Other 1,3-dipoles moved into the focus of investigations and interesting reactivities have been revealed, as demonstrated, for example, by the work of Raines and co-workers.[‌83‌] Highly reactive 1,3-dipoles that can be produced in situ through irradiation paved the way to spatiotemporal click reactions.[‌93‌,‌117‌] 1,3-Dipolar cycloadditions of alkenes can therefore provide functionality that exceeds that of basic conjugation methods. We are looking forward to seeing more interesting developments in this class of reactions in the field of click chemistry.

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