Thiyl radicals alkenes

Thiyl radicals, RS-, may be obtained by hydrogen abstraction from RSH, and will then add readily to alkenes by a chain reaction analogous... 

A review has been published on the methods of functionalization of tetrazoles for the period 2001 to mid 2005 <06RJOC469>. The search for new radical structures having both low selectivity and high reactivity toward the addition reaction onto alkenes has led to a new tetrazole-derived thiyl radical <06JOC9723>. 

In a similar manner, many additions of heteroatom radicals to unsaturated positions have been studied. In many cases, addition reactions of heteroatom radicals to alkenes are reversible and thermodynamically disfavored, but their occurrence is apparent. For example, the rapid addition and elimination of thiyl radicals to unsaturated fatty acid methyl esters results in isomerization reactions from which kinetic parameters can be obtained. Additions of group 14 (IV A) metal-centered... 

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. 

The addition of thiyl radicals to alkenes or alkynes to initiate tandem sequences has also been explored. A highly stereo-controlled phenyl thiyl radical addition, 10-endo macrocyclization, termination process has been used to furnish the macrocycle (37) from the dimethylacrylic ester (36).48 In other work the vinyl radical (38) fonned from addition of a thiyl radical to an enyne gives a mixture of the three products (39)-(41) formed either by 6-exo cyclization (39), addition into the aromatic ring followed by trapping with AIBN (40), or rearomatization and fragmentation to give the sulfide (41) (Scheme 15).49... 

Carbon monoxide has been used to scavenge OH fonned from the ozonolysis of alkenes. The CO2 tints generated was detected by FTIR spectroscopy and the "OH yields for individual reactions were calculated.239 The significance of the OH-induced intramolecular transformation of glutathione thiyl radicals to a-aminoalkyl radicals has been discussed with respect to its biological implications.240 The kinetics and mechanism of the process indicated that it could be a significant pathway for the selfremoval of glutathione thiyl radicals in vivo. 

Alkenes were cleaved to aldehydes by 5 mol% of a (salen VCl complex in the presence of air and thiophenols in 58-95% yield. Other V(III) and V(IV) catalysts are similarly effective. The reaction involves an initial thiyl radical addition to the olefin and trapping by oxygen. The resulting peroxyl radical is in turn most likely transformed to an alkoxyl radical by the catalyst and undergoes -fragmentation to form the most stable radical [198]. 

The early woric with thiyl radicals primarily involved the intramolecular cyclization of alkenes. The reaction appears to be useful since high yields and stereoselective formation of products are observed (equation 7). Under a variety of conditions the diallyl diester (12) produces a 6 1 mixture of stereo-isomeric cyclopentanes (13) and (14) in high yield. ° When enynes are treated with thiyl radicals, low to moderate yields of addition products are observed (equation 8). ... 

It has long been known that unsymmetrical ketones can be prepared by the reaction of aldehydes with alkenes under free-radical reaction conditions. Recently the revision of this chemistry has been reported by the Roberts group [42], They introduced thiols as a polarity reversal catalyst for the addition of aldehydes to alkenes. Thiyl radicals are electrophilic, and therefore a polar Sh2 type transition state for the hydrogen transfer step from an aldehyde would be ideal in this situation. Indeed, the addition of aldehydes to a variety of alkenes can be effected by... 

Irradiation of the thiopyran derivative (292a) results in extrusion of HNCS and the formation of the pyridine (292b, 63.3%) as the major product. The photochemical reactivity of the pyranthione (293) is concentration dependent in 3-methylpentane as solvent. At low concentrations the thione reacts with the solvent but at higher concentrations the main reaction is the production of thiyl radicals. Laser flash photolysis has been used to identify that the triplet excited state of (294) is involved in addition reactions which occur to electron deficient alkenes such as acrylonitrile giving (295), for example. Other compounds related to thiourea are also photochemically reactive. Thus the photochemical cyclisation of (296) to afford (297) has been reported. ... 

It should be noted that to a small extent the diastereoselectivity of the overall process depends on the substituents of the thiyl radical. An attractive feature of this method is the ability to use simple alkenes without acceptor groups, e.g. limonene, as coupling partners. Besides, only stoichiometric quantities of the olefin have to be employed. 

This concept turned out to be useful for a variety of transformations, including reductions, epimerizations [14], hydrosilylations of alkenes, hydrostannations of al-kynes [15] and carbon-carbon bond formation [13]. As an example, thiols catalyze the cyclization of acyl radicals [16a] and masked acyl radicals [16b] these reactions have no preparative value in the absence of thiols because the nucleophilic radicals resulting from the cyclization step are not able to abstract efficiently a hydrogen atom from the starting material, whereas thiyl radicals can (Scheme 2). 

The additions of thiyl radical to alkenes and alkynes can also occur intra-molecularly, thus leading to sulfur heterocycles. This subject has been explored by Surzur s group [32-33]. Based on steric and stereoelectronic factors, the Baldwin-Beckwith rules [34] predict the 5-exo ring closure as the favored pathway. Scheme 6 shows that the pent-4-enylthiyl radical, generated from the allyl sulfide, yields both five- and six-membered rings, in the ratio of 1 19. The predominance of the larger cycle, in contrast with the above-mentioned rules, is due to the reversibility of the reaction. The product distribution reflects a thermodynamic control. 

The observation that thiyl radicals are able to isomerize alkenes was first made by Walling et al. many years ago [55] and, now the addition-elimination sequence of the phenylthiyl radicals is an established methodology in fine chemical synthesis [56]. It has been utilized as key step in the synthesis of biologically active compounds, such as (-)-gloeosporone [57a], (-l-)-hitachimycin [57b] and other naturally occurring macrolides [5b], as well as for preparing non-natural isomers of phospholipids [58]. 

The isomerization mechanism, shown in Scheme 12, is based on the fragmentation of the /i-thioalkyl radical represented by 7 and 8, formed upon addition of thiyl radicals to the double bond, which affords the two geometrical isomers of the starting alkene in an E/Z ratio determined by their thermodynamic stability [59]. 

Scheme 12. Mechanism of thiyl radical-mediated isomerization of alkenes...

The synthesis of carbocyclic compounds from acyclic precursors can be accomplished by a sequence of radical reactions, where thiyl radicals act as catalysts. As an example, the generation of homoallyl radicals through the addition of phenyl-thiyl radical to the double bonds of vinyl cyclopropanes results in the multi-step synthesis of cyclopentanoids [62]. The mechanism is shown in Scheme 13. Feldman and coworkers have demonstrated that the success of this strategy is based on the coupling of vinyl cyclopropanes with the electronically complementary functionalized alkenes. A judicious choice of substituents R and X accelerates the rate limiting step (c). 

The reactivity of alkenes towards thiyl radicals decreases in the... 

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