Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides

Jan Dommerholt, Floris P.J.T. Rutjes*, Floris L. van Delft

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

111 Citations (Scopus)

Abstract

A nearly forgotten reaction discovered more than 60 years ago—the cycloaddition of a cyclic alkyne and an organic azide, leading to an aromatic triazole—enjoys a remarkable popularity. Originally discovered out of pure chemical curiosity, and dusted off early this century as an efficient and clean bioconjugation tool, the usefulness of cyclooctyne–azide cycloaddition is now adopted in a wide range of fields of chemical science and beyond. Its ease of operation, broad solvent compatibility, 100 % atom efficiency, and the high stability of the resulting triazole product, just to name a few aspects, have catapulted this so-called strain-promoted azide–alkyne cycloaddition (SPAAC) right into the top-shelf of the toolbox of chemical biologists, material scientists, biotechnologists, medicinal chemists, and more. In this chapter, a brief historic overview of cycloalkynes is provided first, along with the main synthetic strategies to prepare cycloalkynes and their chemical reactivities. Core aspects of the strain-promoted reaction of cycloalkynes with azides are covered, as well as tools to achieve further reaction acceleration by means of modulation of cycloalkyne structure, nature of azide, and choice of solvent.

Original languageEnglish
Article number16
JournalTopics in Current Chemistry
Volume374
Issue number2
DOIs
Publication statusPublished - 1 Apr 2016

Keywords

  • Azide
  • BCN
  • Cyclooctyne
  • DIBAC
  • Strain-promoted cycloaddition

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