Radical reactions Barton-McCombie

The Barton-McCombie process is an important synthetic tool for the generation of radical species. Me3SiO-(SiHMeO)n-SiMe3 works as a stoichiometric reductant in the tin-catalyzed reaction since Bu3Sn(OPh) is reduced to Bu3SnH as shown in Scheme 31 [71]. 

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]. 

An interesting neophyl-type radical rearrangement process has been established for the synthesis of azabicycles, which are not readily accessible by other means. Barton McCombie deoxygenation of xanthate 70 under slow addition of (TMS)3SiH and AIBN in refluxing toluene furnished the 2-azabenzonorbor-nane derivative in good yield (Reaction 7.72) [82]. 

Since this is a source of radicals, the reagent can find use in Barton-McCombie Reaction and Dowd-Beckwith Bine Expansion, as well as radical cyclization reactions. 

The Barton-McCombie deoxygenation reaction was invented for use in the manipulation of aminoglycoside antibiotics. It has become a popular method because of the mild conditions employed. Radical reactions have advantages over ionic reactions for carbohydrate chemistry. In this context, there is little neighboring group interference in cationic reactions and little elimination compared with normal nucleophilic displacement reactions. 

D. Crich, On the use of S-(4-alkenyI)-dithiocarbonates as mechanistic probes in the Barton-McCombie radical deoxygenation reaction, Tetrahedron Lett. 29 5805 (1988). 

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). 

This "thiophilic" mode of reaction fits well with the other ionic and radical thiophilic additions on a thiocarbonyl group (see [120], and the Barton-McCombie radical thiophilic addition [227] previously discussed in Sections 4.2.2 and 3.2). With thioaldehydes, both C-C and C-S bonds were formed, as in the following case in which 0-pinene was used to trap thiobenzaldehyde [514] ... 

The initiation of the Barton Decarboxylation ( Bu3Sn-H -> Bu3Sn-) is effected with a radical initiator, and as with the Barton-McCombie Deoxygenation, the driving force for the reaction itself is the formation of the stable S-Sn bond. 

Radical deoxygenation of alcohols is important, and the reduction of xanthates prepared from alcohols, with Bu3SnH in the presence of AIBN is called the Barton-McCombie reaction (eq. 2.13) [37-51]. The driving force for the reaction is the formation of a strong C=0 bond from the C=S bond, approximately 10 kcal/mol stronger. This reaction can be used for various types of substrates such as nucleosides and sugars. Though methyl xanthates, prepared from alcohols with carbon disulfide and methyl iodide under basic conditions are very frequently used, other thiocarbonates, as shown in eq. 2.14, can also be employed. 

The Barton-McCombie reaction of bicyclo[3.1.0]-, [4.1.0]-, and [5.1.0]-imidazoylthio-carbonates (264) induces the formation of cyclopropylcarbinyl radicals, and subsequent (3-cleavage, to generate one-carbon ring-expanded 6-, 7-, and 8-membered compounds (265) in good yields [271]. The driving force of these reactions is the reduction of ring strain (eq. 3.106). 

In 2005, Wood and co-workers reported a conceptionally new version of the Barton-McCombie reaction by using water as hydrogen-atom source for the reduction of free radicals in the presence of trialkylboranes (Scheme 35) [85]. 

The reaction of triethylboron with oxygen is a convenient way to generate ethyl radicals at room temperature, or at lower temperatures. These conditions at room temperature in the presence of tributyltin hydride efficiently perform the Barton-McCombie deoxygenation reaction. Recently, we showed that the tin hydride could be replaced by diphenylsilane also at room temperature, for the deoxygenation of secondary alcohols.20 Many different thiocarbonyl derivatives can now be used for the Barton-McCombie reaction. Data were collected for R = Ph, />-F-C6H4, C6F5, C6C13H2 with various substrates (Scheme 2). The yields were excellent for all the secondary... 

All compounds of the arachidonic acid cascade as well as many peptides and biotin contain the carboxyl function. After seeing the value of the Barton-McCombie reaction, it was logical to consider if similar chemistry could be carried out with the carboxyl function.1 In particular, decarboxylation to the corresponding radical seemed a promising way to replace -C02H by -H. 

Tin hydride 2 prepared from hydroxyl acid behaves like the conventional Bu3SnH in standard free-radical reactions, but the tin-containing by-products are easily removed by mild hydrolysis which converts them into base-soluble materials. The performance of these tin hydrides is evaluated for a range of radical reactions involving halides, selenides, Barton-McCombie deoxygenation, and enyne cyclizations.72... 

The use of polymer-supported tin hydrides is now a well-estabhshed method for minimizing tin contamination in products resulting from radical reactions. A new version of the Barton-McCombie deoxygenation reaction has been developed by Dumartin [4] which combines the use of a polymer-supported tin hydride with a stoichiometric silane reductant, giving an attractive catalytic process. 

Decarboxylation of the aliphatic esters of A-hydroxypyridine-2-thione by tributyltin hydride leads to reduction of the radical and the formation of the alkane lacking the carboxyl carbon, as in the Barton-McCombie reaction (Scheme 3.61). 

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