Pyrolysis xanthates, Chugaev elimination

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. 

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. 

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). 

Cram demonstrated that the Chugaev reaction is a syn elimination by showing that the pyrolysis of the S-methyl xanthate of diastereomeric 3-phenyl-2-butanols is stereospecific, as shown in equations 10.72 and 10.73.As noted, the eliminations also produced 3-phenyl-l-butene (in 30-40% yield). 

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. 

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