Click chemistry beyond metal-catalyzed cycloaddition

Abstract

The overwhelming success of click chemistry encouraged researchers to develop alternative "spring-loaded" chemical reactions for use in different fields of chemistry. Initially, the copper(I)-catalyzed azide-alkyne cycloaddition was the only click reaction. In recent years, metal-free [3+2] cycloaddition reactions, Diels-Alder reactions, and thiol-alkene radical addition reactions have come to the fore as click reactions because of their simple synthetic procedures and high yields. Furthermore, these metal-free reactions have wide applicability and are physiologically compatible. These and other alternative click reactions expand the opportunities for synthesizing small organic compounds as well as tailor-made macromolecules and bioconjugates. This Minireview discusses the success and applicability of new, in particular metal-free, click reactions.