Thiocarbonates, Barton-McCombie

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]. 

Barton-McCombie deoxygenation is not always stereoselective the diastereo-meric ratios strongly depends on the nature of the protecting groups and of the ester moiety. However, in 2-C-trifluoromethyl-2-deoxyfuranose, the a compound is the major product of the reaction, due to steric hindrance of this a side. In 3-C-trifluoromethyl-3-deoxyfuranose, deoxygenation by tributyltin hydride yields only the a product, if it is performed with oxalate instead of thiocarbonate. Another possibility to obtain this selectivity is to perform the reaction with 1,2,5,6-di-O-isopropylidene-a-D-glucofuranose (Figure 6.34). ... 

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. 

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

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. 

Xanthates and also thiocarbonates are useful for deoxygenation of an alcohol moiety. " The reaction, called the Barton-McCombie deoxygenation, involves treatment of the derived xanthate or thiocarbonate with n-BugSnH in the presence of an initiator such as AIBN, as shown below. 

The preparation of the CD building block was continued as follows. After reductive opening of the epoxide 91 with sodium cyanoborohydride, the resulting diol was converted into the bis-acetyl ester 92. Selective hydrolysis of the less sterically hindered ester was followed by conversion of the unprotected alcohol into the thiocarbonate. After deoxygenation via a Barton-McCombie reaction, the ensuing product 93 is set up for deprotection and oxidation to a key chiral CD intermediate for vitamin D synthesis. 

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. 

Fu and coworkers developed a variant of the Barton-McCombie deoxygenation which employs a catalytic amount of the tin component with an alternate stochiometric reductant. The reduction of a thiocarbonate 33 by tin hydride (9) yields product 34 and 0=C=S. The BusSn-OPh by-product 35, can be reduced by a stochiometric silyl hydride 37, such as poly(methyl)hydrosiloxane (PMHS), to regenerate 9 and generate PMHS-OPh 36. 

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