Thiols radical additions

The C=C bonds in sulfamoyl-protected imidazoles 765, 767 are electrophilic in nature and can be functionalized either through thiol radical addition 766 or palladium-catalyzed hydride reduction 768 (Scheme 187) <2005HCA707>. In the case of 768, both C=C and C=0 functions are reduced. 

The formation of C-S bonds by thiol radical additions to unsaturated sugars has also been reported, such as the addition of thiolacetic acid to glycal 167 [111]. Giese... 

Thiol-ene polymerization was first reported in 1938.220 In this process, a polymer chain is built up by a sequence of thiyl radical addition and chain transfer steps (Scheme 7.17). The thiol-ene process is unique amongst radical polymerizations in that, while it is a radical chain process, the rate of molecular weight increase is more typical of a step-growth polymerization. Polymers ideally consist of alternating residues derived from the diene and the dithiol. However, when dienes with high kp and relatively low A-, monomers (e.g. acrylates) are used, short sequences of units derived from the diene are sometimes formed. 

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). 

The postmodification strategy, in which apoly(glycydyl methacrylate-co-ethylene dimethacrylate) monolith was activated with hydrogen sulfide to a thiol-modified monolith and subsequently derivatized with an 0-9-(tert-butylcarbamoyl)quinine selector by radical addition reaction, yielded slightly less efficient capillary columns. However, this procedure has the advantage that only minute amount of chiral selector are needed to end-up with a useful enantioselective capillary column [84]. 

Thiol-promoted addition of a variety of silyl radicals to the aromatic moiety of camptothecin (15) is also reported [32]. The addition occurs predominantly at C7 and C12 positions depending on temperature. At 105 °C, mixture of 7-silyl (favoured) and 12-silyl camptothecins are formed alongside substantial amounts of recovered camptothecin. At 160 °C, 12-silyl isomers are formed preferentially, but the total mass balance is substantially reduced. 

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

Phenol-induced oxidative stress mediated by thiol oxidation, antioxidant depletion, and enhanced free radical production plays a key role in the deleterious activities of certain phenols. In this mode of DNA damage, the phenol does not interact with DNA directly and the observed genotoxicity is caused by an indirect mechanism of action induced by ROS. A direct mode of phenol-induced genotoxicity involves covalent DNA adduction derived from electrophilic species of phenols produced by metabolic activation. Oxidative metabolism of phenols can generate quinone intermediates that react covalently with N-1,N of dG to form benzetheno-type adducts. Our laboratory has also recently shown that phenoxyl radicals can participate in direct radical addition reactions with C-8 of dG to form oxygen (O)-adducts. Because the metabolism of phenols can also generate C-adducts at C-8 of dG, a case can be made that phenoxyl radicals display ambident (O vs. C) electrophilicity in DNA adduction. 

Thiepane (35) has been synthesized by an intramolecular radical addition of the thiyl radical (equation 59) which was generated by photolysis of a thiol (71TL2025). Similarly, C—S bond formation has been achieved (equation 60) by an intramolecular condensation of 6-mercaptohexanoic acid to give the thiolactone, thiepan-2-one (135) (64MI51700). A Dieckmann-type base-catalyzed cyclization of a diester precursor followed by acid-catalyzed hydrolysis and decarboxylation has been used in the synthesis of thiepan-3-one (41) as indicated in equation (61) (52JA917). 

This reaction is based on a stoichiometric reaction of multifunctional olefins (enes) with thiols. The addition reaction can be initiated thermally, pho-tochemically, and by electron beam and radical or ionic mechanism. Thiyl radicals can be generated by the reaction of an excited carbonyl compound (usually in its triplet state) with a thiol or via radicals, such as benzoyl radicals from a type I photoinitiator, reacting with the thiol. The thiyl radicals add to olefins, and this is the basis of the polymerization process. The addition of a dithiol to a diolefin yields linear polymer, higher-functionality thiols and alkenes form cross-linked systems. 

For substituted tricyclo[4.1.0.02,7]heptanes, similar addition of benzenethiol in diethyl ether gave an isomeric mixture of bicyclo[3.1.1]heptanes.35 As shown in the mechanistic scheme, the 1,3-disubstituted patterns of the bicyclo[3.1, l]heptanes are governed by the regiospecific attack of the thiol radical on the sterieally less hindered bridgehead carbon. The results of these radical additions arc summarized for bicyclo[n.l.l]alkanes (Table 8)35 and bicyclo[1.1.0]butanes (Table 9). 

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 ... 

Where it is possible to distinguish the products, thiol additions show stereospecificity. The products of addition of hydrogen sulfide, thio-phenol, and thiolacetic acid to 1-chlorocyclohexene are to be 75%, 94%, and 66% cis-l, 2-disubstituted cyclohexane, respectively.88 The addition of thiolacetic acid is less stereopecific than the other thiols. The stereospecificity apparently depends upon the ratio of addendum to 1-chlorocyclohexene, Phenylthiyl radical addition to 1-methylcyclo-... 

Thiols (RSH) cleave a( the sulfur-hydrogen bond on irradiation, and this allows the preparation of sulfides by subsequent radical addition to an alkene (5.62). Hydrogen sulfide behaves in the same way (5.631, and long-chain thiols are made commercially for use as modifiers in emulsion polymerization. 

Some strategies used for the preparation of support-bound thiols are listed in Table 8.1. Oxidative thiolation of lithiated polystyrene has been used to prepare polymeric thiophenol (Entry 1, Table 8.1). Polystyrene functionalized with 2-mercaptoethyl groups has been prepared by radical addition of thioacetic acid to cross-linked vinyl-polystyrene followed by hydrolysis of the intermediate thiol ester (Entry 2, Table 8.1). A more controllable introduction of thiol groups, suitable also for the selective transformation of support-bound substrates, is based on nucleophilic substitution with thiourea or potassium thioacetate. The resulting isothiouronium salts and thiol acetates can be saponified, preferably under reductive conditions, to yield thiols (Table 8.1). Thiol acetates have been saponified on insoluble supports with mercaptoethanol [1], propylamine [2], lithium aluminum hydride [3], sodium or lithium borohydride, alcoholates, or hydrochloric acid (Table 8.1). 

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. 

In the field of thiochemistry, the photocatalytic synthesis of mercaptans represents an interesting chemical route. Schoumacker et al. [60] performed the synthesis of propan-1-thiol by addition of H2S on propene in contact with illuminated Ti02 or CdS catalysts, according to a reaction mechanism implying photogenerated SH radicals. 

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