Xanthates, Barton-McCombie deoxygenation

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). 

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]. 

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 Barton deoxygenation (or Barton-McCombie deoxygenation) is a two-step reaction sequence for the reduction of an alcohol to an alkane. The alcohol is first converted to a methyl xanthate or thioimidazoyl carbamate. Then, the xanthate or ihioimidazoyl carbamate is reduced with a tin hydride reagent under radical conditions to afford the alkane. Trialkylsilanes have also been used as the hydride source. Reviews (a) McCombie, S. W. In Comprehensive Organic Synthesis Trost, B. M. Fleming, I., Eds. Pergamon Press Oxford, U. K., 1991 Vol. 8, Chapter 4.2 Reduction of Saturated Alcohols and Amines to Alkanes, pp. 818-824. (b) Crich, D. Quintero, L. Chem. Rev. 1989, 89, 1413-1432. 

Addition of carbon radicals to carbon-carbon double bonds is an important reaction that can be carried out under hydrogen transfer conditions [27], Peroxides are usually used as radical precursors and an application of this chemistry is presented in Scheme 3 (Eq. 3.1). More recently, reduction of alkyl radical by C-H hydrogen donor has been examined in order to find an environmentally friendly alternative to tin hydride. Zard has reported a simple and cheap alternative to tin hydride for Barton-McCombie deoxygenation reactions [80]. Heating of xanthates derived from carbohydrates in 2-propanol in the presence of dilauroyl peroxide affords the de-oxygenated products in good yields (Scheme 17, Eq. 17.1). 2-Propanol functions as... 

Examples of application of the iert-dodecanethiol/silane couple include typical reductive dehalogenations, but also Barton-McCombie deoxygenations of alcohols, through conversion of the latter into xanthate esters (eq 6), hydrosilylations of alkenes (eq 7), and preparation of silanethiols. The thiol can also be used as a polarity reversal catalyst in conjunction with tris(trimethylsilyl)silane and hexabutyldistannane/malonic acid. ... 

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... 

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 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]. 

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%). 

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 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... 

Figure 7.20 Barton-McCombie reaction, (a) Classic pathway for deoxygenation of secondary alcohols Bu3Sn SCOSCH3 loses COS under the reaction conditions to yield Bu3SnSCH3 (b) Competing reactions in the deoxygenation of primary xanthates, and their avoidance (c) Chugaev reaction of tertiary methyl xanthates.

Use of Tin Hydrides. From the mechanistic point of view, the reductive elimination of methyl xanthate derivatives of (3-hydroxy sulfones entails an interesting variation of the Julia reaction since an initial fragmentation of the C-0 bond through a Barton-McCombie-type radical deoxygenation takes place. Final aryl sulfonyl radical elimination affords the corresponding alkene (Eq. 52).98,99... 

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... 

Radical deoxygenation of sec.-alcohols, Barton-McCombie reaction.2" This reaction proceeds more rapidly with xanthates [ R CHOC(S)SCHr than with any of the known phenoxy thiocarbonyl derivatives [R2CHOC(S)OCf,H ]. Of these the unsubstituted phenoxythiocarbonyl derivative is slightly more reactive than the 2,4,6-trichloro- or the p-fluorophenyl derivative. The pentafluorophcnyl derivative, R2CHOC(S)OC6F5, is the slowest of all known derivatives. 

Examination of the various steps in the above sequence provides considerable insight. From a thermodynamic standpoint several factors are important. In the first instance, the conceptual link between acylthiohydroxamate chemistry and the elegant Barton-McCombie reductive deoxygenation of xanthates and similar thiocarbonyl derivatives is immediately apparent, inasmuch as the reaction involves formation of the strong carbonyl bond at the expense of a weak thiocarbonyl moiety. The enhancement of the aromatic character which occurs when the pyridine nucleus... 

Deoxygenation of alcohols This reaction can be effected by conversion of an alcohol to a derivative that undergoes radical reduction by a hydrogen atom donor (Barton-McCombie reaction). Xanthates are usually employed as the intermediate but... 

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