Elimination Reaction Xanthate Ester Pyrolysis

CHUGAEV ELIMINATION REACTION (XANTHATE ESTER PYROLYSIS) 

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. 

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. 

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. 

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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). 

Certain esters (Chapter 9) are specifically designed to produce alcohol derivatives that are more labile than the alcohols themselves. The special case of the xanthate ester (the Chugaev reaction, Scheme 8.69) has often been used to effect elimination when temperatures for simple ester pyrolysis are too high and other processes intrude. 

The same products, but in different ratios, occur in the gas phase eliminations of HCl from bornyl and isobornyl chlorides and from the pyrolysis reaction of bornyl and isobornyl benzoates and methyl xanthates . The isobornyl reaction is appreciably faster than that of the bornyl ester ((iso-B/B) = 6.8 at 345 °C), but proceeds at a slightly slower rate than that of cyclohexyl acetate, (CH/iso-B) = 2.1 at 600 °K. By analogy with the nonclassical carbonium ion interpretation of the solvolysis rates of bornyl and isobornyl chlorides, the participation of nonclassical carbonium ion intimate ion-pairs, e.g. 

For four- or five-membered cyclic transition states, pyrolysis only leads to beta-elimination if the C -H and C -X bonds can eclipse so as to ensure the necessary proximity for reaction. The syn nature of the amine oxide decomposition has been demonstrated by elimination from the diastereoisomeric pairs of the 1,2-diphenylpropyl system. In the cyclohexyl series, an eclipsed transition state is only achieved if elimination proceeds through the boat conformer and consequently the pyrolysis of 1-methylcyclohexylamine oxide gives an almost quantitative yield of the less stable exo-olefin. This orientation contrasts markedly with that of the six-membered cyclic transition states of the corresponding esters and xanthates which yield predominantly the endo-olefin, syn-clinal stereochemistry being preferred. For all the other ring... 

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