Chugaev elimination reaction

CHUGAEV ELIMINATION REACTION (XANTHATE ESTER PYROLYSIS)... 

In the late stages of the total synthesis of dihydroclerodin, A. Groot and co-workers used the Chugaev elimination reaction to install an exocyclic double bond on ring Before employing the xanthate ester pyrolysis, the authors tried several methods that failed to convert the primary alcohol to the exocyclic methylene functionality. The corresponding xanthate ester was prepared followed by heating to 216 °C in n-dodecane for 2 days to afford the desired alkene in 74% yield. 

This mechanism of a -elimination reaction is supported by experimental findings with " S- and C-labeled starting materials." The Chugaev reaction is analogous to the ester pyrolysis, but allows for milder reaction conditions—i.e. it occurs at lower temperatures. It is less prone to side reactions, e.g. the formation of rearranged products, and is therefore the preferred method. 

The Chugaev elimination is of synthetic value, because it proceeds without rearrangement of the carbon skeleton. Other non-thermolytic elimination procedures often lead to rearranged products, when applied to the same substrates. However applicability of the Chugaev reaction is limited if the elimination is possible in more than one direction, and if a /3-carbon has more than one hydrogen. Complex mixtures of isomeric olefins may then be obtained. For example the thermolysis of xanthate 12, derived from 3-hexanol yields 28% S-hex-3-ene 13, 13% Z-hex-3-ene 14, 29% -hex-2-ene 15 and 13% Z-hex-2-ene 16 ... 

In Figure 4.14, we learned about the Chugaev elimination in connection with the synthesis of alkenes. The second (primary) product of this reaction is the dithiocarbonic acid 5-methyl ester (A). It equilibrates with the zwitterion B, which decomposes into carbon oxysulfide (a heterocumulene) and methanethiol (a heteroatom nucleophile). 

J.M. Cook and co-workers accomplished the total synthesis of ellacene (1,10-cyclododecanotriquinancene) by utilizing the Weiss reaction and the Chugaev elimination as key steps.The elimination of the fris-xanthate was performed in HMPA at 220-230 °C in very high yield. This pyrolysis was superior to the elimination conducted under neat conditions. 

Related reactions Chugaev elimination, Cope elimination, Hofmann elimination ... 

A number of synthetically useful elimination reactions proceed thermally, with no base or acid required. These elimination reactions proceed through a concerted retro-ene mechanism. (The mechanism is sometimes called E,.) The thermal elimination of acetic acid from alkyl acetates and the elimination of RSCOSH from alkyl xanthates (the Chugaev reaction) are retro-ene reactions. 

Although other xanthates have been used, methyl xanthates (R3 = Me) are by far the most commonly employed in the Chugaev elimination. For the preparation of the xanthate, a variety of bases have been used including sodium hydride, sodium hydroxide, sodium amide, and sodium/potassium metal. In the case of pure chiral alcohol stereoisomers, epimerisation of the alcohol stereocentre, under the basic conditions, can occur (with the corresponding xanthates leading to different products). Purification of the xanthate, prior to pyrolysis, is often a problem and it is usual to pyrolyze the crude xanthate directly. Pyrolysis of the xanthate is often carried out by distillation. Depending on the pyrolysis temperature, pressure, and the boiling point of the olefin, the product will either distill with the other products (COS, thiol) or remain in the reaction flask. 

As mentioned previously, the Chugaev elimination has found particular use in the field of terpenoid chemistry, not only in structural studies, but also in synthesis. For example, a tandem Claisen rearrangement-ene reaction of geraniol derivative 23 gave... 

In terms of modified operational procedures for the transformation, in their route to (-)-kainic acid, Ogasawara and co-workers performed a tandem Chugaev elimination-intramolecular ene reaction and found sodium hydrogen carbonate to be a beneficial additive.27 Derivative 35 was heated in refluxing diphenyl ether and in the presence of sodium hydrogen carbonate. This furnished tricyclic system 36, which was converted to (-)-kainic acid. They later extended this procedure for the synthesis of the acromelic acids.28... 

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