Following Sharpless' visionary characterization of several idealized reactions as click reactions, the materials science and synthetic chemistry communities have pursued numerous routes toward the identification and implementation of these click reactions. Herein, we review the radical-mediated thiol-ene reaction as one such click reaction. This reaction has all the desirable features of a click reaction, being highly efficient, simple to execute with no side products and proceeding rapidly to high yield. Further, the thiol-ene reaction is most frequently photoinitiated, particularly for photopolymerizations resulting in highly uniform polymer networks, promoting unique capabilities related to spatial and temporal control of the click reaction. The reaction mechanism and its implementation in various synthetic methodologies, biofunctionalization, surface and polymer modification, and polymerization are all reviewed.

Thiol–Ene Click Chemistry

The merits of thiol-click chemistry and its potential for making new forays into chemical synthesis and materials applications are described Since thiols react to high yields under benign conditions with a vast range of chemical species, their utility extends to a large number of applications in the chemical, biological, physical, materials and engineering fields This critical review provides insight into emerging venues for application as well as new mechanistic understanding of this exceptional chemistry in its many forms (81 references)

Thiol-click chemistry: a multifaceted toolbox for small molecule and polymer synthesis

Thiol-ene “click” reactions and recent applications in polymer and materials synthesis

As a tribute to Professor Charlie Hoyle, we take the opportunity to review the impact of thiol-ene chemistry on polymer and materials science over the past 5 years. During this time, a renaissance in thiol-ene chemistry has occurred with recent progress demonstrating its unique advantages when compared with traditional coupling and functionalization strategies. Additionally, the robust nature of thiol-ene chemistry allows for the preparation of well-defined materials with few structural limitations and synthetic requirements. To illustrate these features, the utility of thiol-ene reactions for network formation, polymer functionalization, dendrimer synthesis, and the decoration of three-dimensional objects is discussed. Also, the development of the closely related thiol-yne chemistry is described. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 743–750, 2010

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/pola.23824

The power of thiol-ene chemistry

No copper needed: In recent years, a large number of metal-free click reactions have been reported based on thiol-ene radical additions, Diels–Alder reactions, and Michael additions. In this Minireview, special attention is given to the advantages and limitations of the different methods to evaluate whether they have the potential to surpass the overwhelming success of the copper(I)-catalyzed azide-alkyne cycloaddition.

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.

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Click Chemistry beyond Metal-Catalyzed Cycloaddition

The radical addition of mercaptans (RSH) onto poly[2-(3-butenyl)-2-oxazoline], which is available through a living/controlled cationic isomerization polymerization, can proceed smoothly in the absence of side reactions, exhibiting the characteristics of a click reaction. The “thio-click” reaction can be performed under feasible ([RSH]/[CC] ∼ 1.2−1.5, no transition metal additives) and mild conditions (generation of radicals with UV light at room temperature) and goes to completion within a day. Hydrophobic fluoropolymers can be prepared in the same way as water-soluble (co-)polymers or glycopolymers, starting from readily available materials.

Thio-click modification of poly [2-(3-butenyl)-2-oxazoline]

In this study, it is shown that preparative density gradient ultracentrifugation can be applied to separate racemate crystals from excess enantiomer crystals. This was demonstrated for alanine crystals separated in a 50 wt % Nycodenz gradient. The recovery rates of the pure enantiomers from the mixtures were good (70−90%), and the separation method showed accuracy in the third digit of the density. As such density differences between racemate and enantiomers can be found for a wide range of crystalline chiral compounds, the presented separation method should be applicable to a large variety of substances on a preparative scale.

Separation of Racemate from Excess Enantiomer of Chiral Nonracemic Compounds via Density Gradient Ultracentrifugation

31P Molecular testing, treatment and outcome of patients with advanced solid tumors harboring a NTRK1, NTRK2 or NTRK3 gene fusion: Study design and first results of the REALTRK registry

and Antje Völkel

Papers

Thio-click modification of poly [2-(3-butenyl)-2-oxazoline]

Separation of Racemate from Excess Enantiomer of Chiral Nonracemic Compounds via Density Gradient Ultracentrifugation

31P Molecular testing, treatment and outcome of patients with advanced solid tumors harboring a NTRK1, NTRK2 or NTRK3 gene fusion: Study design and first results of the REALTRK registry