Thiol ene coupling

One of the most useful and widely used applications in the synthesis of natural product derivatives relies on the efficient photoaddition of RS-H onto a double bond (a reaction known as thiol-ene coupling) [55], The reaction exploits the weakness of the S—H bond that can be cleaved homolytically under irradiation (atca. 254nm). The electrophilic sulfur-centered radical attacks a nucleophilic double bond, thus starting a radical chain reaction. 

In 2008, Gruttadauria and coworkers synthesised prolinamide derivatives 54a and 54b, in which prolinamide units were anchored to a polystyrene support via thiol-ene coupling reactions. In the presence of these heterogeneous catalysts, cyclic ketones or acetone 8 reacted with atyl aldehydes 9 to afford corresponding chiral aldols 10 (Scheme 10.l). The best yields of 10 and stereoselectivity of the reactions (dr antilsyn) 96 4-98 2 and 89-99% ee) were attained in a 1 2 (v/v) water/chloroform solvent system, in which water pushed reagents to the concentrated organic phase where asymmetric reactions occurred, meanwhile chloroform ensured swelling of the polymer chain. However, the activity of catalysts 54a and 54b became... 

Click Chemistry in Polymer Science CuAAC and Thiol-Ene Coupling for the Synthesis and Functionalization of Macromolecules... 

Thiol-ene coupling was also used for the end-functionaHzation of PNIPAM in an analogous study conducted by the groups of Lowe and Hoyle [55]. In this case, PNIPAM was prepared by RAFT polymerization, followed by the aminolysis of the thiocarbonylthio end group to produce a terminal thiol simultaneous Michael addition with aUyl methacrylate yielded the alkene mono end-functional PNIPAM. The polymer terminus was then modified via a radical thiol-ene dick reaction with three different mercaptans to afford a series of PNIPAM polymers with varied LCSTs (Scheme 30.5). 

Scheme 30.19 The rapid synthesis of a sixth-generation dendrimer using an orthogonal AB2 — CD2 divergent growth approach employing both thiol-ene and CuAAC click coupling reactions, (i) Thiol-ene coupling (ii) CuAAC (iii) Thiol-ene coupling (iv) CuAAC (v) Thiol-ene coupling (vi) CuAAC. Reproduced with permission from Ref [133] 2010, American Chemical Society.

Scheme 1 Mechanism of CuAAC as proposed by Sharpless and co-workers in 2005." 6.11.1.2 Thiol-Ene Coupling History and Reaction Details...

Epoxidation, hydroformylation, dimerisation, thiol-ene coupling, oxidative cleavage, and olefin metathesis attack the double bonds of unsaturated oils, fatty acids, or fatty acid esters. These reactions have been exploited for the synthesis of interesting monomers from renewable resources [1-3,13,14]. 

Quantification of the thiol-ene coupling was carried out by H-NMR and revealed, in all cases, reduction of the double-bond peak at =5.4 ppm in the spectra of the final product. This finding suggested that the efficiency of thiol-ene coupling was >75% for the reaction undertaken with the thiol with an internal ester moiety, and >95% for reactions carried out with the aliphatic thiol incorporating an internal amide moiety. Values of molecular weight after functionalisation were 16-26 kDa. 

In some cases, an end blocker such as YR SiRjOSiRjR Y is used to form reactive -OSiR R Y chain ends. Interesting examples include triaryl-amines,nitrobenzoxadiazole fluorescent groups via thiol-ene coupling. Homopolymerizations of this type are discussed in detail elsewhere. - ... 

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