Alcohols 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. 

Organic chemists have been aware of reversible addition-fragmentation involving xanthate esters in organic chemistry for some time. It is the basis of the Barton-McCombie process for deoxygenation of alcohols (Scheme 9.37).402 404... 

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). 

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]. 

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],... 

The keto group of the trisubstituted dioxanone 133 generated by ozonolysis was removed by radical deoxygenation according to the Barton-McCombie protocol [80] via the alcohols 134 and the corresponding xanthate, leading after deben-zylation to the dioxane 135 in excellent yield. After conversion to the tosylate, cleavage of the acetonide and protection of the secondary alcohol function as a TBS ether provided access to oxirane 128 by cyclization with NaH in 99% yield and in virtually diastereo- and enantiomerically pure form (de, ee > 96%). 

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... 

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

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 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... 

Besides carbon-halogen bonds, Bu3SnH is used routinely for hydrogenolysis of various carbon-heteroatom bonds. The deoxygenation from alcohols has been performed by a Barton-McCombie reaction where the addition of tin hydride to the triple bond is suppressed (Equation (2)).29-31... 

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

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... 

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. 

Hong, F.-T., Paquette, L. A. BusSnH-catalyzed Barton-McCombie deoxygenation of alcohols. Single-step process for the reductive deoxygenation of unhindered alcohols. Chemtracts 1998,11, ST-72. 

Boussaguet, P., Delmond, B., Dumartin, G., Pereyre, M. Catalytic and supported Barton-McCombie deoxygenation of secondary alcohols a clean reaction. Tetrahedron Lett. 2000,41, 3377-3380. 

In addition to the reduction of organic halides, which is the usual test experiment," supported tin hydrides can also be used in the Barton-McCombie deoxygenation of alcohols " (which can be achieved... 

The products were obtained in excellent yields after simple hexane extraction. The removal of bromine and iodine proceeded smoothly. The removal of PhSe afforded methylcyclohexanone, indicating that the decarbonylation of acyl radicals takes place. The efficiency of deoxygenation of alcohols (Barton-McCombie reaction) is independent of the type of thiocarbonyl derivative (i.e. 0-arylthio-carbonate, O-thioxocarbamate, thiocarbonylimidazole or xanthate), as previously reported for (TMS)3SiH in organic solvents.25... 

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