Radical addition of thiols

Konig et al. have achieved thioether functionalization of T8[CH = CH2]8 via the radical addition of thiols such as thiophenol, cyclohexylthiol, and 2-mercaptopyridine in the presence of azobisisobutyronitrile (AIBN) as a radical initiator (Table 13), while Gao et al. have also used this method to prepare very highly functionalized POSS by reacting T8[CH = CH2]8 with thiol-terminated glycosides giving glycoclusters in 70% yield (Figure 22). 

Scheme 44. Radical addition of thiols and dithiols 200 onto bicyclopropylidene (1) [135]...

Work on radical addition of thiols prior to 1940 has been summarized by Mayo and Walling.181 The reaction may be initiated photochemi-cally in the absence of oxygen or peroxides even at 0°C.208 light of wavelength 3000 A. is required, but, in the presence of photosensitizers such as acetone, the longer wavelengths transmitted by Pyrex are effective. The reaction steps may be written ... 

Thioethers have also been prepared on cross-linked polystyrene by radical addition of thiols to support-bound alkenes and by reaction of support-bound carbon radicals (generated by addition of carbon radicals to resin-bound acrylates) with esters of l-hydroxy-l,2-dihydro-2-pyridinethione ( Barton esters Entry 6, Table 8.5). Additional methods include the reaction of metallated supports with symmetric disulfides (Entries 7-9, Table 8.5) and the alkylation of polystyrene-bound, a-lithiated thioani-sole [65],... 

The radical addition of thiols to alkenes, another general route to sulfides, was found [22] to be initiated by 9-BBN, leading to a remarkably efficient and simple method for the preparation of dialkyl sulfides. 

The present work reports such an approach with the synthesis of (vinyl)polystyrene polyHIPEs and their functionalisation by free radical addition of thiols to the remaining unsaturations. The interest of such materials is proven by the presentation of an application of a thiol functional support in free radical reduction of alkyl halides. 

Scheme 2 Free-radical addition of thiols to (vinyl)polystyrene polyHIPE...

Thus, it is possible to use this reaction to obtain new macromolecules (di-ols or diamines) with low glass-transition temperature (Tg) and no crystalline phase. Earlier works suggested the synthesis of hydroxy-telechelic oligomers by radical addition of thiol onto dienes. But, the products obtained showed poor solubility in organic solvents and a high melting point. Our process, however, improves the properties of diol compounds (better solubility and decrease of the melting point). 

Aliphatic polysulfides of the type -(-S—R—S—R -)- are produced by the free radical addition of thiol groups onto substances with vinyl double bonds ... 

Octasilsesquioxanes with general formula Rs(SiO. s)g tue cube-shaped molecules with eight functional groups [1, 2], Various functionalities can be used to synthesize different molecular structures of high synunetry. One method to prepare those structures is the radical addition of thiols to double bonds initiated by AIBN [3,4]. 

The thiol-ene type of cure is based on free-radical additions of thiols to unsaturated compounds. The unsaturated compounds are often, though not necessarily, allylic ftmctionalized resins, such as allyl ethers and allylic urethanes and ureas. The thiol-ene systems find application in poly(vinyl chloride) based flooring and in gaskets. 

This reaction is not specific to radiolysis, and the initiating free radicals may also be generated thermally or photochemically. The general field of free radical addition of thiols to unsaturated compounds has recently been reviewed . ... 

Levesque " has observed that dithioacids (221) add to alkenes under AIBN initiation to give 1,3-dithiolanes (223) in high yield when the alkene is of the styrene type. This must involve intrlamolecular addition of the radical 222 to the sulfur atom (Scheme 94). Analogous results are obtained in the free radical addition of thiols to compounds 224 [X = Ikyl, OMe, NMc2, or SMe Z = CHj, (CH2)2, O, or S] where the radical 225 adds intramolecularly to the sulfur atom to give 226. 

Radical addition of thiol or thiol-modified support to the vinyl group gives the respective thioether linkage 34 and represents one of the most convenient ways to immobilize Cinchona alkaloids [163, 172]. There are also few examples of platinum-catalyzed hydrosilylation of Cinchona alkaloids toward 11-silyl-substituted derivatives 35 with the use of monomeric silanes or polysiloxane polymers [173-175]. De Vries reported rhodium-catalyzed hydroformylation of the four main members of Cinchona alkaloids carried out on a hundred gram scale. Under optimized condition, linear aldehydes 36 were selectively obtained with the yield over 80% [176]. 

The free radical addition of thiols to olefins provides TOtentially versatile method for antioxidant adduct formation in rubbers. This is shown for nitrile-butadiene rubber in Scheme 1, but it is applicable in principle to any rubber which has a reactive double bond. Three main methods have been used to carry out the reaction. 

All these observations can be rationalised by assuming the mechanism of polymerisation to be similar to free-radical addition of thiols to olefins as outlined next. 

Direct alkylation has been achieved in special circumstances. Thus 2-(trimethylsilyl)ethyl sulfides, obtainable from alkylation of 2-(trimethylsilyl)ethanethiol or by radical addition of thiols to vinyl trimethylsilane, react with a-glycosyl bromide with the assistance of Ag(I) activation to offer a general synthesis of 8-thioglycosides. Yields generally vary (34-99%), and the fi a ratio can be quite high (eq 10). ... 

Formation of Sulfonyl Chlorides. Wmyltrimethylsilane undergoes the free radical addition of thiols to form the 2-thioethyl-trimethylsilane. Oxidation to the sulfoxide and reaction with sulfuryl chloride provides 2-chloroethyltrimethylsilane and the sulfonyl chloride in good yield (eq 24). The reaction sequence works well for the preparation of alkyl, aryl, and unsaturated sulfonyl chlorides. 

Figure 2.10 (a) The UV-promoted radical addition of thiols to alkynes - the thiol-yne reaction (b) kinetics of the thiol-yne reaetion monitored via FT-IR spectroscopy (Chan et ai, 2009a). DMPA 2,2-dimethoxy-2-phenylacetophenone. (Reprinted with permission from J.W. Chan, C.E. Hoyle and A.B. Lowe, Sequential phosphine-eatalyzed, nucleophilic thiol-ene/radical-mediated thiol-yne reactions and the facile orthogonal synthesis of polyfunctional materials, Journal of the American Chemical Society, 131, 16, 5751-5753, 2009. 2009 American Chemical Society.)... 

Measurements for seventeen reactions showed a generally smooth dependence of kn/ o upon the heat of reaction, calculated from the bond dissociation energies of reactants and products, and gave maximum effects for nearly thermoneutral reactions. Qualitatively similar trends have been reported by Lewis in the radical additions of thiols [79] and hydrogen bromide [80] to olefins. 

As with all condensation reactions, thiol-ene polymerizations are sensitive to the stoichiometry of the thiol- and ene-containing monomer substrates. Typically, the best results are obtained when there is a molar equivalent concentration of thiol and double bonds present. Recently, there has been a considerable effort to extend the photoinduced radical addition of thiols to alkynes (the so-called thiol-yne reaction). 

SCHEME 2.198 Synthesis of N-(P-alkylthioethyl)pyrroles by free-radical addition of thiols to N-vinylpyrroles. 

The system AIBN/CClj promotes the radical addition of thiols to N-vinylpyrroles giving rise to p-adducts. For example, from 2-phenyl-N-vinylpyrrole and ethane- and butanethiols, the corresponding N-(p-alkoxyethyl)-2-phenylpyrroles are synthesized in 54% and 50% yields, respectively [660],... 

Thiols primarily add to electron-deficient alkenes by free radical and nucleophilic mechanisms. In the presence or absence of radical initiators, the free radical addition of thiols to alkenes can lead to conjugate addition products. More conveniently, thiol conjugate addition reactions can be cata-... 

Even in the absence of catalyst, thiols add to alkynes under neutral conditions to afford a f -Markovnikov-type vinyhc sulfides with excellent regioselectivity usually as a stereoisomeric mixture. Indeed, the reaction of benzenethiol with 1-octyne in the absence of transition metal catalyst provides a t/-Markovnikov adduct 4a regioselectively with the E Z ratio of ca. 1 1. This hydrothiolation takes place, most probably via the radical process induced by trace amounts of oxygen existed in the reaction system. The radical addition of thiols to alkynes sometimes seems to proceed even in the presence of transition metal catalysts. Accordingly, when the a f -Markovnikov adducts are obtained with approximately equal amounts of E- and Z-isomers, the following possibility is present the anti-Markovnikov adducts are formed by the radical process, regardless of the presence of transition metal catalysts. 

Scheme 13 Radical addition of thiols to unsaturated amino acid derivatives.

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