Thiocarbonyl derivatives deoxygenation

An unexpected C-arylation was observed by Sherburn et al. in an attempted radical deoxygenation of a homoallylic secondary alcohol 83 via its thiocarbonyl-derivative 84 (scheme 17).1511 Thus, reaction of 84, obtained from 83 with ArOC(=S)Cl, with nBu3SnH yielded the 10-aiyl compound 87 As inter-... 

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 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]. 

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

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... 

Free Radical Deoxygenation of Thiocarbonyl Derivatives of Alcohols... 

The relative rates of acylation and of deoxygenation have been determined with these various reagents [44]. As expected, the pentafluoro reagent reacts the fastest with an alcohol under standard conditions, followed by the 4-fluoro reagent, and the phenyl derivative is the slowest. However, for the deoxygenation reaction the fastest group is the methyl xanthate. The slowest is the pentafluorophenyl derivative. This is not important because all of the thiocarbonyl derivatives mentioned give very fast radical reactions 144],... 

This chapter shows how radical chemistry based on thiocarbonyl derivatives of secondary alcohols can be useful in the manipulation of natural products and especially in the deoxygenation of carbohydrates. From the original conception in 1975, the variety of thiocarbonyl derivatives used has increased, but the methyl xanthate function still remains the simplest and cheapest, when other functionality in the molecule does not interfere. Otherwise, selective acylation with aryloxythiocarbonyl reagents is important. Many of the functional groups present in carbohydrates and other natural products do not interfere with radical reactions. 

D. H. R. Barton, D. O. Jang, and J. Cs. Jaszberenyi, On the mechanism of deoxygenation of secondary alcohols by tin hydride reduction of methyl xanthates and thiocarbonyl derivatives, Tetrahedron Lett., 31 (1990) 3991-3994. 

Thiocarbonyl derivatives are deoxygenated on treatment with (Bu4N)2S208 and sodium formate in DMF in excellent yields. The deoxygenation is proposed to be... 

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... 

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... 

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. 

The starting xanthate 1 is easily obtained by treatment of the requisite alcohol with base (e.g. NaOH, KOH, NaH, KH, or BuLi), carbon disulfide, and methyl iodide, normally in this order, but variations have been reported where all the ingredients are mixed in the presence of a phase transfer catalyst [4]. Thus, the overall transformation is a deoxygenation of the initial alcohol ROH into the corresponding alkane RH. Other thiocarbonyl derivatives are also suitable as substrates for the deoxygenation thiocarbonyl imidazolides [1], O-aryldithiocarbonates [5], or even certain thiocarbamates [6]. These derivatives are often easier to introduce than a xanthate, but are more expensive. 

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... 

The preparation of simple deoxy-sugars by reductive radical methods such as deoxygenation of thiocarbonyl derivatives of alcohols is now considered a routine operation [135] and is therefore not discussed here. Photochemical chemical reduction of halides, for example the photolysis of primary iodides for the preparation of... 

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