Radical thiophenyl

Irradiation of phenyldisulfide cleaves the weak S—S bond to give a pair of thiophenyl radicals. One of these then adds to the less-substituted olefinic carbon of 25 to generate the tertiary alkyl radical 26 (Scheme 14.5). Bond rotation then ensues to give the more stable rotamer 27 in which there is minimal steric repulsion between the C(7)-methyl and the tetrahydrofuran framework. Elimination of the thiophenyl radical from 27 finalises the isomerisation to alkene 19. 

In addition to the well exploited radical additions to enamides, thiovinyl ethers have been shown to be suitable intramolecular acceptors for aryl radicals. By placing a thiophenyl substituent on terminal alkene of 33, the cyclization to 34 occurred exclusively in the 6-exo mode and was not complicated by internal hydrogen abstraction from the allylic positions of the alkene (Scheme 13) [83, 84]. 

F 2-(thiophenyl)vinyl diastereoselective radical acetaldehyde Mannich equivalent... 

As an alternative to tin-mediated conditions, thiyl radicals are an attractive alternative they generate carbon-centered radicals upon reversible addition to a multiple bond. This was found to be effective for cyclizations of 49E and 49F (Scheme 13). Treatment with AIBN and PhSH, followed by fluoride-induced desilylation, afforded vinyl and 2-(thiophenyl)vinyl adducts 50E and 50F, respectively [122, 123, 125]. Interestingly, during fluoride-induced (TBAF) desilylation of the intermediate formed... 

In a study of SRN1 photoreactions of halothiophenes with phenylthiolates anions, phenylthiothiophene radical anions are formed and the yield of the expected phenylthiothiophene product is limited by the bond rupture in this intermediate the thiophenylthiolate anion is formed and detected as thiomethyl ether after quenching of the reaction by methyl iodide. By adding benzonitrile as an extra electron acceptor, the bond rupture may be controlled and the selectivity of the reaction has been improved in favour of the thiophenyl ether but at the expense of the overall reaction rate [118]. 

One of the earliest radical cyclization cascades initiated by addition of S-centered radicals to alkynes was reported in 1987 by Broka and Reichert (Scheme 2.25). Thiophenyl radicals, PhS, which were generated under radical chain conditions, undergo addition to the terminal end of the C = C triple bond in enyne 138. The resulting vinyl radical 141 can undergo cychzation in both 6-endo (preferred) and 5-exo fashion, and reduction of the radical intermediates 142 and 143 leads to the final observed products 139 and 140, respectively. 

C-Glycosides. Thiophenyl glycosides undergo ready free-radical allylation with allyl- or methallyltri- -butyltin. Thus the L-lyxose derivative 1 reacts with allyltri-/ -butyltin under photochemical initiation to give 2 and 3 in the ratio 90 10. The reaction... 

Miscellaneous Reactions.- A photochemical 1,3-migration is reported in the conversion of the thiophenyl sulphone (34) into the isomer (35). Irradiation of the fluoroalkene (36) results in the formation of the reduced-dechlorinated product (37) and the product (38), the result of a 1,2-phenyl migration. The compounds produced in this reaction are influenced by solvent and by the nature of the second halogen. Radical and cationic intermediates are thought to be involved. 

An additional example illustrating the utility of thiophenyl glycosides in free radical mediated C-glycosidations was reported by Waglund, et a/.6 As shown in Scheme 5.2.4, 1-methylcarboxy-l-phenylthioglycosides were treated with allyltributyltin and irradiated with ultraviolet light. The resulting C-allyl derivatives were formed in approximately 30% yields with the stereochemical... 

S -Phenyl chlorothioformate was used as a radical trap in the radical-mediated carboxylation approach (Scheme 18) [40b]. Among several carbonyl derivatives including phosgene and bis(thiophenyl) carbonate, 5-phenyl chlorothioformate gives the best result and works with primary, secondary, and tertiary alkyl iodides. In addition to the desired thioester, a small amount of the corresponding sulfide is isolated as a by-product. 

Rapid elimination of an atom or a group at the y9-position of the radical, such as bromide or thiophenyl, to suppress the opening of the cyclopropylmethyl radical... 

The initial step is the addition of a thiophenyl radical to the double bond. After fast ring opening of the cyclopropylcarbinyl radical, the critical event is the addition of the resulting radical to the olefin. If this intermolecular reaction is slow, trapping by a second equivalent of the thiophenyl radical leads to the formation of an undesired by-product. 

Only activated olefins, e.g. a,yS-unsaturated carbonyl compounds, enolethers, and enolacetates, are good radical acceptors in these reactions. The olefins have to be used in five- to tenfold excess. The overall transformation is completed by elimination of the thiophenyl radical. Thus, diphenyl disulfide, the source of thiophenyl radicals, can in principle be employed in substoichiometric amounts. The diaster-eoselectivity of vinylcyclopentane formation is difficult to control, and mixtures of diastereomers are often obtained. A highly stereoselective example is shown in Scheme 3. 

The synthesis of vinylcyclohexanones through fragmentation of oxygen-substituted vinyl cyclopropanes has also been reported (Scheme 5) [7]. After addition of the thiophenyl radical to the olefin, benzophenone is extruded to yield an unsaturated enol radical. The reaction sequence is completed as described above for the [3+2] annulation. 

Reductive lithiations of substituted tetrahydropyrans are often highly stereoselective reactions as a direct consequence of the anomeric radical intermediates involved. The mechanism involves one-electron reduction of a thiophenyl ether (or an equivalent reactive functional group) to generate an axial anomeric radical that is reduced by a second electron to form an axial a-alkoxylithium species, which can then be alkylated or protonated. Thus the high selectivities observed in reductive lithiations are a direct reflection of the axial preference for a-oxygenated radicals. 

Similarly, through a sequence forming four carbon carbon bonds, Saicic was able to assemble the all-carbon triquinane 23 from acyclic precursor 22 with good diastereoselectivity [14]. No tin derivative is necessary, since a final yff-elimination of the thiophenyl radical propagates the radical chain. 

Exploration of the template controlled free-radical oligomerization of other activated olefins began with standard monomers utilized in bulk polymer synthesis and the template 63. Vinyl acetate and acrylonitrile led only to uncontrolled polymerization, while vinylene carbonate did not react under the standard experimental conditions. More exotic monomers, such as vinyl trifluoroacetate and rert-butyl acrylate, were also unsuccessful. Only methyl acrylate polymerization was arrested by template 64 to provide the macrocyclized product 96 in modest yield as a mixture of five diastereomers (Scheme 8-25). Subsequent studies with the more effective thiophenyl-bearing template 63 at lower temperatures improved this yield to 35%. The diastereomer distribution was reminiscent of the methyl methacrylate-derived product, although no stereochemical assignments were made in this case either. 

In the case of thiophenyl, ionic and radical reactions appear to take place simultaneously. 

In another synthetic application, the alkylation products of (1) undergo facile thermal elimination of methanol to afford (.5- 1-phenylthio- 1-trimethylsilylalkenes in good yields with high stereoselectivity (eq 10). The elimination is facilitated by oxygen and is further accelerated by the addition of triethylborane, which implies the involvement of a radical pathway. The resulting (. -l-phenylthio-l-trimethylsilylalkenes are transformed into ( )-vinylsilanes by reductive cleavage of the thiophenyl group with lithium naphthalenide (eq 11). ... 

In principle, any kind of reactive radical may undergo this type of displacement. Examples from organic chemistry include thiophenylation [17] and organosulfur coupling to a metal-organic component [19], reactions (7) and (8) ... 

---