Alcohols Chugaev elimination

The superfluous carbonyl oxygen atom was removed by carbonyl reduction to provide the alcohol 171, subsequent Chugaev elimination (via 172 to 173) and double bond hydrogenation with in situ generated diimide (Scheme 27) [94]. The isopropenyl double bond was finally re-established by reductive cleavage of the a-bromo ether unit in 173 to afford the fully functionalized enantiomerically pure A-ring building block (162). 

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. 

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. 

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 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. 

Chugaev reaction. Formation of olefins from alcohols without rearrangement through pyrolysis of the corresponding xanthates via cis elimination. 

Some intramolecular eliminations that occur thermally are known as pyrolytic eliminations, and many of these reactions result in syn elimination. Often these reactions are carried out in the gas phase, where they are not affected by solvent, counterions, or other species that can affect reactions in solution. One of the most-studied pyrolytic eliminations is the Chugaev reaction (equation 10.70). Reaction of an alcohol having a j8-hydrogen atom with sodium or potassium metal or with a strong base... 

The heating of xanthates usually results in /3-elimination and formation of olefins (Chugaev reaction ). However, when there is no /3-hydrogen at the alcohol moiety, rearrangement takes place. A kinetic study of the influence of substituents on the reaction rate of a series of diaryl xanthates to diaryl dithiocarbonates (81->82) again indicates a four-membered cyclic transition state . A similar transition state is indicated, by the same... 

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. 

Acid-sensitive t-alcohols can be dehydrated by a process that is related to the Chugaev reaction but which takes place at much lower temperatures (refluxing THF) (Scheme 9). u/c-Diols react with iodoform, triphenylphosphine, and imidazole to give the corresponding olefin, probably via reductive elimination from a di-iodo intermediate this method is particularly useful for preparing unsaturated sugars. 

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