Barton-McCombie procedure

Thus glycosylation with a 2-0-acetyl-3,4,6-tri-0-benzyl-manno- or gluco-pyranosyl bromide leads to 1,2-/ra ,v-a-D-mannopyranosides and 1,2-trans-fi-v>-glucopyranosides, respectively, with acetoxy functions at C-2. Deoxygenation at this position by deacetylation, followed by xanthation and reduction with tributyltin(IV) hydride in the presence of azoisobutyronitrile (Barton-McCombie procedure) will give 2-deoxy glycosides with the a-D-((3-L-) and (3-d- (a-L-) configurations respectively.71... 

Additionally, the reduction process of Barton and McCombie has been developed into a useful technology. The Barton-McCombie procedure (Scheme 8.22) involves the conversion of an alcohol to a thiocarbonate (or dithiocarbonate) derivative (usually in two steps) and the reaction of the latter with tributyltin hydride and azobisisobutyronitrile (AIBN) (bis(l-cyano-l-methylethyl)diazine, [(CH3)2C(CN)N=NC(CN)C(CH3)2]). As shown in Scheme 8.22, decomposition of AIBN produces a radical, which, in turn, abstracts hydrogen from tributyltin hydride, generating the tributyltin radical. The reaction of the latter with sulfur and the subsequent decomposition of that intermediate produces a deoxygenated. 

The 3, 5CO-(TIPDS) protection is also reported in the ribonu-cleosides under similar experimental conditions. For example, the base-modified derivatives 1, 2, and 3 are obtained in 61%, 91%, and 57% yield, respectively. In all these cases, the regioselective protection of 3 and 5 positions is followed by 2 -deoxygenatlon reaction by the Barton-McCombie procedure, and it results In the preparation of 2 -deoxyribo analogs (eq 7). 

Alcohol Deoxygenation. A limitation of the useful Barton-McCombie procedure for the deoxygenation of alcohols is its application to tertiary alcohols because of difficulties in preparing the required xanthate or other derivatives. A solution to this is to first form a monoester with Oxalyl Chloride and then react the remaining acyl chloride function with the sodium salt (3) (eq 6). In these reactions, although r-butanethiol is suitable as the chain carrier, in some cases 3-ethyl-3-pentanethiol gives superior yields (50-90%). The intermediate tertiary radicals can be trapped by powerful Michael acceptors such as 1,2-dicyanoethylene. 

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]. 

One approach started from partially protected rhamnosyl derivatives. Thus, from easily obtained 2,3-<3-isopropylidene-a-L-rhamnopyranoside, deoxygenation at C-4 by the Barton and McCombie procedure afforded the 4,6-dideoxy-a-L-/yxo-hexopyranoside derivative.234... 

In the Barton-McCombie radical deoxygenation reaction the hydroxyl group of an alcohol is replaced with a hydrogen atom. Even hindered secondary and tertiary alcohols may be deoxygenated by this method. In a typical procedure the alcohol is first converted to a thioxoester derivative, which is then exposed to tri-n-butyltin hydride in refluxing toluene. 

This procedure Illustrates a simple, general method for the rieoxygenation of secondary hydroxyl groups. It is particularly useful for reducing hindered alcohols. The method was first described hy Barton and McCombie who have reviewed a number of other examples. ... 

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