Barton—McCombie reaction

Scheme 22. The Barton-McCombie reaction [R1R2CHOH— R1R2CH2].

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]. 

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. 

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). 

Interestingly, when a fi-substituted alcohol is used in the Barton-McCombie reaction and if a [3-elimination process occurs faster than the hydrogen transfer step, then the formation of a double bond is observed. We have just seen such an example with a dixanthate (see Section 3.1.3). Many others are known as in [3-hydroxy sulfides [231] and [3-hydroxysulfones [232,233] in a modified Julia synthesis of olefins. 

J. Nicholas Kirwan, B. P. Roberts, and C. R. Willis, Deoxygenation of alcohols by the reactions of their xanthate esters with triethylsilane An alternative to tributyltin hydride in the Barton-McCombie reaction, Tetrahedron Lett., 31 (1990) 5093-5096. 

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). 

Barton-McCombie reaction of imidazole thiocarbonates with Bu3SnH... 

One great advantage of the Barton-McCombie reaction is that acetal, ketone, ester, hydroxy, and amino groups are not affected during the reaction [6-18]. Polystyrene-supported di-/i-butylstannane can reduce a thiocarbonyl derivative under the same... 

Barton-McCombie reaction with Bu2POH and (PhC02)2... 

Both Bu3SnH and (Me3Si)3SiH are able to reduce alkyl iodides or bromides but not alcohols. However, in the Barton-McCombie reaction, they reduce certain alcohol derivatives, namely, ones that contain a C=S double bond (e. g., thiocarboxylic esters or thiocarbonic esters). Figure 1.39 shows how the OH group of cholesterol can he removed by means of a Barton-McCombie reaction. The C=S-containing alcohol derivative used there is a xanthate. 

Fig. 1.40 Propagation steps of the Barton-McCombie reaction in Figure 1.39.

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]. 

Scheme 35 Barton-McCombie reaction in the presence of trialkylboranes and water...

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. 

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