Deoxygenation of alcohol

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... 

Scheme 5.9 illustrates some of the conditions that have been developed for the reductive deoxygenation of alcohols. Entries 1 to 4 illustrate the most commonly used methods for generation of thiono esters and their reduction by tri-M-butylstannane. These include formation of thiono carbonates (Entry 1), xanthates (Entry 2), and thiono imidazolides (Entries 3 and 4). Entry 5 is an example of use of dimethyl phosphite as the hydrogen donor. Entry 6 uses r .s-(trimethylsilyl)silane as the hydrogen atom donor. 

Scheme 5.9. Deoxygenation of Alcohols via Thiono Esters and Related... 

A modification of the azolide method for deoxygenation of alcohols is the conversion of the thiocarbonylimidazolide with methanol into the thionocarbonate, which is then treated with tri-w-butyl stannane/AIBN. Thus, 2,3-dideoxynucleosides (a), (b), and a secodeoxynucleoside (c) have been prepared as follows [52H56]... 

Deoxygenation of Alcohols with Concomitant Elimination or Rearrangement... 

Intramolecular deoxygenation of alcohols containing double and triple bonds (such as hydroxyalkynes or hydroxynitriles) with ImCSIm leads via the corresponding thio-carbonylimidazolides to five- and six-membered cyclized systems with exocyclic double bonds.[72]... 

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). 

A relevant reductive process, which has found wide application in organic synthesis, is the deoxygenation of alcohols introduced in 1975 by Barton and McCombie [58]. Reaction (4.28) shows that the thiocarbonyl derivatives, easily obtained from the corresponding alcohol, can be reduced in the presence of BusSnH under free radical conditions. The reactivity of xanthates and thiocarbonyl imidazolides [58] was successfully extended to 0-arylthiocarbonates [59] and (9-thioxocarbamates [60]. Several reviews have appeared on this subject, thus providing an exhaustive view of this methodology and its application in natural product synthesis [61-64]. 

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]. 

Deoxygenation of alcohols by means of radical scission of their corresponding thiocarbonyl derivatives. 

Aliphatic alcohols are not reducible under electrochemical conditions. Conversion to a suitable anionic leaving group however does allow carbon-oxygen bond cleavage. Thus, methanesulphonates are reduced at a lead electrode under constent current conditions and this affords an overall tw o step process for the conversion of alcohols to alkanes [9].Deoxygenation of alcohols by this route has been applied successMly in the presence of other functional groups which are difficult to reduce such as alkene, epoxide, ester and nitrile. Cyclopropanes are formed in 50-97 %... 

Tri-/ -butyltin hydride also serves as a hydrogen-atom donor in radical-mediated methods for reductive deoxygenation of alcohols.131 The alcohol is converted to a thiocarbonyl derivative. These thioesters undergo a radical reaction with tri-w-butyltin... 

This procedure gives good yields from secondary alcohols and, by appropriate adjustment of conditions, can also be adapted to primary alcohols.132 Scheme 5.7 illustrates some of the conditions which have been developed for the reductive deoxygenation of alcohols. 

Scheme 5.7. Deoxygenation of Alcohols via Thioesters and Related Derivatives... 

These include thiobenzoates, thiocarbonylimidazolides, and phenyl thionocarbonate esters.6 The S-methyl xanthate ester is a particularly convenient intermediate to prepare because of its ease of formation and the low cost of the reagents. Its use is precluded, however, by the presence of base-labile protecting groups and, in such cases, the thiocarbonylimidazolide or phenyl thionocarbonate ester will generally prove satisfactory. Additional methods for the radical deoxygenation of alcohols are described in a review by Hartwig.7... 

Deoxygenation of alcohols and ethers. Treatment of alcohols and methyl or trlmethylsilyl ethers in acetonitrile with this iodoirimethylsilane equivalent and then zinc (previously activated with aqueous hydrochloric acid) and a little acetic acid results in deoxygenation to alkanes, usually in 60-90% yield. Presumably an alkyl iodide is an intermediate. 

Deoxygenation of alcohols. Alcohols, particularly tertiary ones that can form stable carbanions, are deoxygenated by reaction with potassium and iron carbonyl in toluene. The reduction proceeds through the potassium alkoxidc.1 Examples ... 

Deoxygenation of alcohols.2 Secondary alcohols react with 1 in the presence of pyridine or 4-dimethylaminopyridine to form thiono esters (2), which are cleaved... 

Deoxygenation of alcohols.1 Thiocarbonatc derivatives of alcohols arc conveniently reduced to alkanes by potassium and 18-crown-6 in r-butylamine. 

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

W. P. Neumann and M. Peterseim, Elegant improvement of the deoxygenation of alcohols using a polystyrene-supported otganotin hydride, Synlett, p. 801 (1992). 

D. Schummer and G. Hofle, Tris(trimethylsilyl)silane as a reagent for the radical deoxygenation of alcohols, Synlett. p. 705 (1990). 

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