Barton-McCombie method

The platinum-catalysed cycloisomerization of ene-yne 6.272 to give diene 6.273 was employed in a synthesis of streptorubin 6.277 (Scheme 6.110). After cyclization, the more electron poor of the two double bonds was reduced using a palladium-catalysed reduction with a tin hydride reagent. The ketone 6.274 was reduced and the resulting alcohol was excised by the Barton-McCombie method. The resulting... 

Alcohol 202 on deoxygenation by Barton-McCombie method followed by acid hydrolysis of acetonide and oxidative cleavage with Nal04 gave aldehyde 203, which on subsequent olefination and hydrolysis afforded alcohol 204 (Scheme 6.35). 

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 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. 

Scheme 4 gives the endgame from Corey s cyclization product 4 (Scheme 1) to the marine natural product scalarenedial (20, [15]), which is a strong fish feeding deterrent. The Barton-McCombie process [16] was employed to deoxygenate at C3, followed by conversion of the ketone to the vinyl triflate 18 with PhNTf2 (McMurry s method [17]). After hydroxy-desilylation of 18, the carbonylation to 19 was catalyzed by Pd(dppp) (see above). The vicinal... 

Fig. 1.42. Cyclization of a 5-hexenyl radical intermediate from a Barton-McCombie defunctionalization as a method for cyclopentane annulation (cyclizing defunctionalization, in terms of Figure 1.2 this means a "substitution including a fragmentation and an addition ).

Fig. 1.35. Cyclization of a 5-hexenyl radical intermediate from a Barton-McCombie defunctionalization as a method for cyclopentane annulation.

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. 

A much more common transformation for deoxygenating secondary alcohols is the Barton-McCombie reaction and various modifications of this method. Diisopropylideneglucofu-ranose 23 has served as a model compound for many of these deoxygenation reactions... 

Ammonium formate hydrogenolysis of 7t-allyl-palladium(II) complexes formed via oxidative addition of Pd(0) to propargylic carbonate esters is a useful method for preparing disubstituted alkynes, as depicted below. This method of deoxygenation avoids the use of expensive and toxic reagents often associated with the free-radical Barton-McCombie deoxygenation. °... 

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. 

In the asymmetric synthesis of the C1-C19 fragment of kabiramide C, to complete the stereochemical array, J. Panek and co-workers used, among other methods, the Barton-McCombie deoxygenation protocol. ... 

The xanthate group may be reduced away using any of the methods described above for the Barton-McCombie reaction. The lauroyl peroxide/isopropanol system appears to be especially useful in this respect [32a]. This is demonstrated by the transformation in Scheme 16, a key step in the synthesis of (+)-matrine [32b]. Thus, upon heating in refluxing isopropanol with portion-wise addition of a stoichiometric amount of lauroyl peroxide, the double cyclization is followed by the reductive removal of the xanthate group. The reaction gives a 3 1 mixture of isomers, the minor having the relative stereochemistry of a//o-matrine. 

In 1999, Enders used this method in an iterative fashion to synthesize fl ti-l,3-polyols (Scheme 2.33). The sequence required two diastereoselective alkylations at the a- and a -positions of the hydrazone before cleavage of the chiral auxiliary using an aqueous solution of oxalic acid in ether. The reduction of the resulting ketone followed by a Barton-McCombie deoxygenation furnished the corresponding acetal 17, which was converted to the iodide intermediate 18 upon three additional steps. The latter was then used as an... 

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. ... 

Since its introduction by Barton and McCombie, the deoxygenation of thionocarbonyl derivatives of alcohols has become an important synthetic reaction and a valuable method for the generation of carbon-centered radicals.3-4 Xanthates, thionobenzotes, thionocarbonyl imidazolides, aryloxy thionocarbonate, N-phenylthionocarbamates and oxalate esters are conveniently deoxygenated with tin or silicon hydrides in boiling benzene or toluene.4-5... 

The method is a modification of one used by Barton and McCombie.8 Reduction of ketones.9 Ketones can be reduced to alcohols by Bu3SnH in the presence of either AIBN or a Lewis acid, but this reaction is limited to unhindered ketones. However, even sterically hindered ketones, such as f-butyl methyl ketone, can be reduced under high pressure (10 kbar) in the absence of a catalyst. This method is particularly useful in the case of cyclopropyl and a,p-epoxy ketones, which are reduced to the corresponding alcohols. Reduction of these ketones with Bu3SnH under radical conditions results in ring-opened products. 

For the preparation of a 3 -deoxy Lex analogue, an acylated 3-deoxy-D-. v/o-hexopyranose was used. The latter was prepared either from phenyl 1-thio-D-galactopyranoside78 or from l,2 5,6-di-0-isopropylidene-a-D-galactofuranose,79 via the Barton and McCombie deoxygenation method. 

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