Aldehydes alkylation, Cope rearrangement

As might have been anticipated on the basis of the Cope rearrangement of hydrocarbons, which was extended to alcohols and enols earlier in this chapter (e.g., see Scheme 8.84), alkyl and aryl ethers also enjoy the ability to rearrange (a Claisen rearrangement, vide supra. Scheme 8.43 see Claisen and Tietze, 1925, 1926) to, respectively, isomeric ethers (Scheme 8.99) or ketones (aldehydes) (Scheme 8.100) and phenols (Scheme 8.101). 

An ingenious approach to racemic estrone has used two reactions in a combined tandem Cope-Claisen rearrangement (ref. 130). 1-Bromomethyi-3,4-dihydro-6-methoxynaphthalene is used to alkylate 1-methoxycarbonyl-2-methylcyclopent-2-ene and the ester group in the product converted to a vinyloxymethyl substituent. Thermolysis afforded a mixture of diastereoisomeric aldehydes (2 1) containing a majority of the trans compound. Ozonolysis and epimerisation at the 8-position succeeded by McMurry coupling gave the required tetracyclic structure from which racemic estrone methyl ether was obtained. 

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