Xanthates, Chugaev elimination

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 ... 

The mechanism involves a stereospecific syn-elimination via ion-pair formation from the intermediate sulfamate ester (comparable to the Chugaev elimination of xanthate esters). Kinetic and spectroscopical data are consistent with an initial rate-limiting formation of an ion-pair followed by a fast c s- 3-proton transfer to the departing anion. 

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. 

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. 

Chugaev elimination Thermal syn elimination of xanthate esters to form alkenes. 82... 

Alkyl xanthates 2 are prepared by treatment of an alcohol 1 with a base and carbon disulfide, followed by exposure of the resulting sodium salt with an alkylating agent.1 Pyrolysis of the xanthate 2 to give an alkene 3 is called the Chugaev elimination. 

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. 

Examples involving the pyrolysis of xanthates of primary alcohols are relatively few in number. The preparation of small molecular weight alkenes, for example, I -pentene and isopropylethylene, using the Chugaev elimination has been demonstrated.14 More recently, the heating of xanthate 8 furnished derivative 9, containing an exocyclic double bond. Compound 9 was subsequently converted to the insect-antifeedant dihydroclerodin. 

The utility of the Chugaev elimination for the formation of olefins without rearrangement of the carbon skeleton can be observed upon pyrolysis of the xanthate of alcohol 14.17 The desired vinyl cyclopropane (IS) was isolated in reasonable yield (42%) along with a small amount of the rearranged xanthate. Alternatively, acid-mediated dehydration with sulphuric acid yielded a variety of rearranged products in low yield. Ester pyrolysis (of the acetate of 14) also furnished a variety of compounds, with the major product being cyclopentene 16. 

Multiple Chugaev eliminations of several xanthates within the same molecule are possible. For example, triol 28 was smoothly converted to the corresponding methyl xanthates and subsequently heated to yield ellacene (29), a precursor to the polyquinenes.21 The Chugaev elimination of xanthates derived from 1,2-diols, however, often yields other products such as cyclic thionocarbonates.2... 

The behaviour of tertiary alcohols in the Chugaev elimination mirrors that of primary and secondary systems however, relatively few examples have been reported. The 5-methyl xanthate of dimethylcyclopropylcarbinol 30 was pyrolyzed to give the olefin in 24%... 

The dehydration of cyclic systems is equally possible. As mentioned previously, the elimination is sensitive to steric effects. For example, in the case of cyclohexanol derivative 32a, Chugaev elimination yielded 39% of 33a and 10% 34a. For 32b and 32c, 46% of 33b and 6% of 34b, and 36% of 33c and 10% 34c were received, respectively.23 These results indicate the elimination proceeded as to avoid the formation of a double bond exo to the ring. Interestingly, the temperature required to affect the transformation was 200 °C for 32a and 32b, whereas it dropped to 100 °C for 32c. This is due to the increasing bulk adjacent to the xanthate, decreasing the stability of the xanthate with elimination providing relief of the steric crowding. 

Chugaev elimination [27] This reaction involves the formation of alkenes through pyrolysis of the corresponding xanthates via cis elimination ... 

In some cases, eliminations occur in non-ionizing solvents and without the addition of any base. In these cases the reactant itself has an internal base and a cyclic transition state leads to elimination. The symbolism for the reactions is Ei, standing for elimination, intramolecular. Only heat is required to induce the reaction, and hence these reactions are called thermal eliminations (the term pyrolysis is also sometimes used). Thioesters, xanthates, selenoxides, and N-oxides are common in these reactions. The Cope elimination involves the formation of an N-oxide and subsequent elimination via the pathway shown in Eq. 10.91, and the Chugaev elimination involves xanthate esters [ROC(S)SR]. The Chugaev elimination was shown to follow a syn elimination pathway based on the stereospecific nature of the reaction (Eqs. 10.92 and 10.93). 

The Chugaev elimination of tertiary alcohols is improved by use of the potassium xanthate rather than the 5-methyl xanthate this method cannot be extended to primary or secondary alcohols. Secondary alcohols are dehydrated on heating in hexamethylphosphoramide the transition state (209) is proposed. 

The hydroxyl group is converted to a xanthate, and, after reduction of the carbonyl group, a Chugaev elimination is done (see Section 6.8.3). The final stage of the... 

The Chugaev reaction of S methyl xanthates is a synthetically useful p5u olysiss process. The corresponding electron impact induced elimination is a prominent feature of xanthate mass spectra, (45). > The electron impact induced cleavage is at least partially cfs-stereospecific as the thermal reaction is... 

A concise route to (-)-kainic acid was developed by K. Ogasawara and co-workers by employing sequentially a Chugaev syn-elimination and an intramolecular ene reaction as the key steps.After preparing the xanthate under standard conditions, the compound was heated to reflux in diphenyl ether in the presence of sodium bicarbonate. The desired tricyclic product bearing the trisubstituted pyrrolidine framework was formed as a single diastereomer in 72% yield. 

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. 

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