Reduction thiocarbonyl derivative

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]. 

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... 

Radical chain chemistry is often employed for the transformation of an alcohol to the corresponding deoxy derivative. The secondary alcohol 1 is first converted into a suitable thiocarbonyl derivative. The first derivatives investigated were thioxobenzoates 2, xan-thates 3, and thiocarbonylimidazolides 4 (Scheme 2). On reduction with tributyltin hydride, these derivatives afforded a good yield of the appropriate deoxy compounds [8-10]. 

The reduction of 114 with LAH, followed by reaction with triphosgene, led to benzo[l, 2,5]thiadiazepin-6(4//)-one 1,1-dioxide 115, which upon treatment with Lawesson s reagent gave the corresponding thiocarbonyl derivative 116 (Scheme 26). The 1,2,5-thiadiazepine 115 was acylated by treatment with di-/-butyldicarbonate in the presence of AyV-dimethylaminopyridinc to afford 117, which is alkylated with 3-methyl-2-butenyl bromide or ethyl iodide to give 118 and 119, respectively <2002JHC81>. 

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. 

We explored other thiocarbonyl derivatives including xan-thates (e.g. 19), thionoimidazolides (e.g. 20) and thio-carbonates. The last convert a glycol such as 21a via the thiocarbonate 22 and subsequent tin hydride reduction to mainly the primary alcohol 21b. The intermediate opens in such a way as to afford the more stable radical. This reaction is readily applied to nucleosides.910... 

CHOH >CHi. A variety of thiocarbonyl derivatives of secondary alcohols are reductively cleaved by Bu,SnH. The S-methyl xanthate is a convenient derivative for use in this reaction because of convenience and low cost. ... 

For a given secondary alcohol, the choice of thiocarbonyl derivative is predicated more by structural features (steric hindrance, other functional groups) present in the alcohol than by the actual reductive step. Barton and McCombie reported comparable results for 5-methyldithiocarbonyl (MDC), thioben-zoyl (TB) and imidazole-1-thiocarbonyl (ITC) derivatives, and typical preparations of these are shown in... 

Table 2 Tri-n-butylstannane Reduction of 0-Thiocarbonyl Derivatives of Cholesterol (A) and 1,2,5,6-Di-O-ispropylidene o-glucofuranose (B) in Toluene...

Because the lower degree of stabilization of primary radicals retards the fragmentation (process (A) in Scheme 5), the standard procedure was inefficient for 0-thiocarbonyl derivatives of primary alcohols, but was rendered acceptable by running the reductive step at 150 °C. Conversion of methylhederagenin (77) to monoxanthate (78) followed by heating with Bu3SnH in p-cymene gave methyl oleanolate (79) in 51% overall yield. 

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... 

Dihydro-9-sila-10-heteroanthracenes are a class of radical-based reducing agents. They effect reductive debromination and deoxygenation of alcohols via 0-thiocarbonyl derivatives. ... 

Radical deoxygenation of alcohols by the reduction of thiocarbonyl derivatives with trialkyltin hydrides has been extended to tertiary alcohols by use of the... 

The Baiton-McCombie reaction describes the overall reduction of a 1°, 2°, or 3° alcohol (1) to the parent alkane (3), effectively replacing -OH with -H. Reduction is achieved via pre-activation of the hydroxyl group as its thiocarbonyl derivative (2) followed by reaction with a reducing agent such as tributyltin hydride. The reductive process involves a radical-mediated transformation. 

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