Hydrogen atom abstraction from thiols

Radical reactions have some stereochemical features that can be compared directly with their ionic counterparts, especially when the radical centre is adjacent to an existing stereogenic centre. The tris(trimethylsilyl)silyl radical adds to chiral ketones like 3-phenyl-2-butanone 7.59 to give a radical 7.60 flanked by a stereogenic centre. The hydrogen atom abstraction from a thiol, determines the relative stereochemistry, and the products 7.61 and 7.62 are analogous to those from the hydride reduction of the ketone. They are formed in the same sense, and the stereochemistry is explained by the Felkin-Anh picture 7.60. 

For a long time, thiyl radicals (RS ) have been considered as rather unreactive species. They were formed as a result of a hydrogen atom donation from thiols (RSH) to carbon-centered radicals, in a process responsible for the repair of damage in biological environment. However, the H-atom donation or repair reaction is now known to involve a reversible equilibrium the RS radicals are able to abstract H-atoms. Hence, the common presumption that H-atom donation by RSH is the end of the biological pathway in which RSH repairs radicals is incorrect. 

From a mechanistic standpoint, however, the first method to be developed [22, 4] is of more interest and relied very simply on available kinetic data, which indicated that the capture of an alkyl radical by molecular oxygen is some ten thousand times faster than the competitive hydrogen atom abstraction from a thiol. Thus, the simple passage of triplet oxygen through a solution of the O-acylthiohydroxamate and a non-nucleophilic mercaptan such as fert-butanethiol leads to excellent yields of hydroperoxides (Scheme 18). Whilst these primary products can of course be iso-... 

A typical example of the formation of thiyl radicals by displacement reactions is a hydrogen atom abstraction from a thiol by, for example, a carbon-centered radical, reaction (1) ... 

Thiol-catalyzed Radical-chain Cyclization of Unsaturated Acetals and Thioacetals. When the unsaturated dioxolane 1 and a radical initiator, 2,2-di(t-butylperoxy)butane (DBPB), were heated at 125 °C in octane in the presence of tri(f-butoxy) silanethiol (TBST), the spirocyclic ketal 2 was formed cleanly and isolated in 92% yield (eq 1). When the reaction was performed in the absence of TBST, compound 2 was not detected. TBST is believed to promote the generation of the l,3-dioxolan-2-yl radical 3 by hydrogen-atom abstraction from 1 in a process termed polarity-reversal catalysis (eq 2). 

Finding hydrogen atom abstraction from the thiol is the chain propagating step that produces the chain-carrying thiyl radical rather than electron transfer from a sulfide ion is not unexpected in terms of the expected chemical behavior of the methylene blue derived radical MB. The most probable structure... 

Silverman and Zieske have rationalized how a protein nucleophile other than flavin is involved in MAO inactivation reactions, and why different inactivator compounds specifically react with flavin, protein amino acids, or both (100). Hydrogen atom donation from a cysteine residue to the flavin semiquinone radical would produce a thiyl radical, which could then capture the primary or secondary alkyl radical generated on cyclopropyl ring opening from the amine radical cation of the inactivator. The hydrogen atom abstraction reaction between the flavin and active site amino acid may be an equilibrium process such that either species could be present at any turnover. Hence, a combination of steric constraints and proximity to either the flavin semiquinone radical or the thiol radical will determine the site of adduct formation for a particular inactivator structure. A two-dimensional representation is shown in Scheme 23 (compounds 40-42), which illustrates the proposed equilibrium between the flavin semiquinone radical and amino acid as well as the proposed intermediates for the inactivation of MAO by A-(l-methylcyclopropyl)benzylamine 40 (104), rrradical center relative to the particular protein radical is consistent with proposed site of attachment of inactivator to protein 40 is near the flavin radical, such that exclusive flavin attachment occurs, 41 is positioned closer to the amino... 

In the pH range above that observed for the rate maximum, hydrogen atom abstraction by MB from the thiol (reaction 17) is a rate limiting step in the chain sequence. If termination occurs by reaction 19 and the derived rate law for the reaction (Eq. 25) predicts that the reaction would be half order in MB ... 

Von Sonntag and coworkers14 repeated Michael and Hart s study of the reaction of OH radical with 1,3- and 1,4-cyclohexadienes and extended it. They found that in the case of 1,4-cyclohexadiene, 50% of the OH radicals abstract an hydrogen atom, while only about 25% of the OH radicals abstract an hydrogen atom from 1,3-cyclohexadiene. The remaining OH radicals probably add to the double bond. The addition to the double bond was confirmed by final products analysis in the case of the 1,4-isomer. When N20-saturated aqueous solution of 1,4-cyclohexadiene (10-2 M) together with lower (10-4 M) concentration of the thiol (1,4-dithiothreitol) was y-radiolysed, it was found that 4-hydroxycyclohexene was produced with a yield of 0.29 prnol J 1, i.e. a yield of 50% of the OH radicals (equation 9). 

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