Barton—McCombie deoxygenations

Scheme 7 Barton-McCombie deoxygenation reaction in the presence of (Me0)2P(0)H...

Wood [127] reported an innovative development of the Barton-McCombie deoxygenation of alcohols allowed to work under tin-free conditions. A trimethylborane-water complex proves to be an efficient reagent for the reduction of xanthates. Complexation of water by trimethylborane induces a strong decrease of O - H bond dissociation energy from 116 kcal/mol (water) to 86 kcal/mol (Me3B-water complex). 

Scheme 57 Barton-McCombie deoxygenation with Me3B-water complex...

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]. 

Miller also explored the ASD of glycerol derivatives through an enantioselective acylation process which relies on the use of a pentapeptide-catalyst which incorporates an A-terminal nucleophilic 3-(l-imidazolyl)-(5)-alanine residue [171], Most recently, Miller has probed in detail the role of dihedral angle restriction within a peptide-based catalyst for ferf-alcohol KR [172], site selective acylation of erythromycin A [173], and site selective catalysis of phenyl thionoformate transfer in polyols to allow regioselective Barton-McCombie deoxygenation [174],... 

When the trifluoromethylation occurs on aketonic carbonyl (such as position 2 or 3 in furanose series), it must be followed by a Barton-McCombie deoxygenation of the hydroxyl. It thus leads to the 2- or 3-C-trifluoromethyl deoxyfuranoses. The transformation of these latter compounds into deoxynucleosides has been reported. Trifluoromethyl 2, 3 -dideoxynucleosides and A-2 3 -vinylic nucleosides have also been prepared according to this approach (Figure 6.34). The CF3 group protects the glycosyl base bound from proteolysis in acidic medium, especially in the case of A-2 3 compounds. ... 

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). ... 

BuaSnH-Catalyzed Barton-McCombie Deoxygenation of Alcohols 3-Deoxy-1,2 5,6-Bis-0-(1-methylethylidene)-a-D-Ribohexofuranose. 

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. 

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. 

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... 

In the conjugate reduction of enals and enones, tin hydride is used catalytically by the combination with PhSiH3.58 Barton-McCombie deoxygenation reaction is performed by using Bu3SnH catalyst and PMHS as a stoichiometric reductant (Equation (16)).59... 

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... 

Scheme 8. The Barton-McCombie deoxygenation of alcohols with catalytic rather than stoichiometric amounts of tributylstannane.

Table 2. Barton-McCombie deoxygenation of phenyl thionocarbonate esters comparison of the catalytic with the stoichiometric reaction [25].

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. 

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