Barton radical chain

Alkenyl boronic esters can also be used to trap nucleophilic carbon-centered radicals, which can be generated by the tin hydride method or by decomposition of an organomercurial derivative. The influence of the olefin and boron substituents on the reactivity and regioselectivity has been determined. Vinyl-9-BBN displayed significantly better reactivity than the boronic ester while the directing effect of the boronic ester group is weaker than that of an ester function. The Barton radical chain procedure furnished very stable adducts due to an intramolecular complexation between boron and nitrogen (Scheme 9.12) [29]. Radical additions of various xanthates also occurred smoothly in the presence of lauroyl peroxide [30]. Intermolecular ver-... 

The substitution of a functional group for a hydrogen atom is a very important transformation in synthetic organic chemistry. Barton et al. [10] developed various radical chain defunctionalization reactions using dialkylphosphonates... 

In most other cases, however, the diene system simply becomes too unreactive to participate in radical chain reactions. Thus, the reductive decarboxylation of ester 7 by Barton-POC ester methodology20 or as the selenoester21 gives the reduced product 8, cleanly without any trace of product in which the diene system has participated in the reaction (equation 4)20-21. 

Scheme 35 Barton carbonate PTOC-OMe, a radical chain transfer reagent able to convert a C-centered radical into an O-centered radical (Eq. 35.1) and a radical initiator (Eq. 35.2)...

The reduction of thiocarbonyl derivatives by EtsSiH can be described as a chain process under forced conditions (Reaction 4.50) [89,90]. Indeed, in Reaction (4.51) for example, the reduction of phenyl thiocarbonate in EtsSiD as the solvent needed 1 equiv of dibenzoyl peroxide as initiator at 110 °C, and afforded the desired product in 91 % yield, where the deuterium incorporation was only 48% [90]. Nevertheless, there are some interesting applications for these less reactive silanes in radical chain reactions. For example, this method was used as an efficient deoxygenation step (Reaction 4.52) in the synthesis of 4,4-difluoroglutamine [91]. 1,2-Diols can also be transformed into olefins using the Barton-McCombie methodology. Reaction (4.53) shows the olefination procedure of a bis-xanthate using EtsSiH [89]. 

The addition of silyl radicals to thiocarbonyl derivatives is a facile process leading to a-silylthio adducts (Reaction 5.37). This elementary reaction is the initial step of the radical chain deoxygenation of alcohols or Barton McCombie reaction (see Section 4.3.3 for more details). However, rate constants for the formation of these adducts are limited to the value for the reaction of (TMS)3Si radical with the xanthate c-C6HuOC(S)SMe (Table 5.3), a reaction that is also found to be reversible [15]. Structural information on the a-silylthio adducts as well as some kinetic data for the decay reactions of these species have been obtained by EPR spectroscopy [9,72]. 

J. E. Forbes and S. Z. Zard, A novel radical chain reaction of xanthic anhydrides. Further observations on the intermediacy of alkoxythiocarbonyl radicals in the Barton-McCombie reaction. Tetrahedron Lett. 30 4367 (1989). 

D. H. R. Barton, D. O. Jang, and J. C. Jaszberenyi, Tris(trimethylsilyl)silane and diphenylsilane in the radical chain dideoxygenation of 1,6-anhydro-D-glucose A comparative study, Tetrahedron Lett. 33 6629 (1992). 

In an earlier paper Barton and Onyon considered the unimolecular mechanism of dehydrochlorination to be of more universal application than the radical chain mechanism and postulated that a chloro-compound will decompose by a radical chain mechanism only so long as neither the compound itself nor the reaction products will be inhibitors for the chains . On the basis of this postulate the authors correctly predicted the mechanism of decomposition of a number of chlorine compounds. The postulate does not hold well for bromine compounds which show a greater tendency to decompose via radical chain mechanisms. However, from their early studies on 2-bromopropane 2-bromobutane, t-butyl bromide, and bromo-cyclohexane, Maccoll et a/.234,235,397,410,412 concluded that these compounds also decompose unimolecularly via a four-centre transition state similar to that proposed by Barton and Head. 

The kinetics of this reaction have been studied by Barton, Howlett and a number of other workers Decomposition near 400 °C is characterised by marked induction periods. Howlett reported the induction period to be 12-14 min at 380 °C and to vary with temperature according to the expression 1.6x 10 exp (45,000/Hr) sec. Beyond the induction period, the decomposition was observed to obey a simple first-order rate law, with the rate coefficient expressible ask = 6.5 X 10 exp (47,000/Rr)sec Howlett proposed the following radical-chain scheme to account for the kinetics... 

R.H. Schlessinger et al. have successfully synthesized the a,(3-unsaturated octenoic acid side chain of zaragozic acid, which contains acyclic skip 1,3 dimethyl stereocenters. Their approach utilized the Barton radical deoxygenation reaction in the last step of the total synthesis for the removal of the unnecessary hydroxyl group. 

Barton, D. H. R., Chern, C.-Y., Jaszberenyi, J. C. The invention of radical reactions. XXXIII. Homologation reactions of carboxylic acids by radical chain chemistry. Aust. J. Chem. 1995, 48,407-425. 

Girard, P., Guillot, N., Motherwell, W. B., Hay-Motherwell, R. S., Potier, P. The reaction of thionitrites with Barton esters a convenient free radical chain reaction for decarboxylative nitrosation. Tetrahedron 1999, 55, 3573-3584. 

Barton, D. H. R., Crich, D., Motherwell, W. B. The invention of new radical chain reactions. Part VIII. Radical chemistry of thiohydroxamic esters a new method for the generation of carbon radicals from carboxylic acids. Tetrahedron 1985, 41,3901-3924. 

White phosphorus in THF reacts in a long radical chain reaction with carbon radicals derived from Barton s PTOC esters. Oxidation of the adducts (HgOg or SOg) provides a convenient synthesis of phosphonic acids. For sensitive products the further transformation to phosphonic acids is best carried out with an excess of SO2. The reaction is illustrated by the synthesis of L-2-amino-4-phosphonobutyric acid in 58% yield from L-glutamic acid using the appropriate protecting groups (Scheme 8.91). ... 

A similar beneficial effect of 1,1-diphenylethylene on the yields of arylation products was later observed in the synthesis of benzonitrile derivatives by reaction of diaryliodonium salts with potassium cyanide and in the reaction of diaryliodonium salts with the sodium salt of nitroalkanes. 7 In the latter case, the reaction was therefore considered to result from intermediate inner-sphere radicals. Some years later. Barton et al. showed that 1,1-diphenylethylene acts as an efficient inhibitor of the radical chain process in the reaction of enolates with diaryliodonium salts. They concluded that the arylation products arose from a non-radical process. 

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