Regioselective ether cleavage

Reactions.—New methods for the synthesis and cleavage of benzyl and trityl ethers, and for the cleavage of allyl ethers have been discussed in an earlier section (Protection of Alcohols). Primary and secondary alkyl methyl ethers have been demethylated by the combination boron tribromide-sodium iodide-15-crown-5 The reagent methyltrichlorosilane-sodium iodide is a new combination for regioselective ether cleavage for example aliphatic methyl ethers undergo predominant demethylation to alcohols (for primary or secondary alkyl groups) or iodides (in tertiary cases). 

The Simmons-Smith cyclopropanation method has also found application for the a-methylation of ketones via an intermediate cyclopropane. The starting ketone—e.g. cyclohexanone 9—is first converted into an enol ether 10. Cyclopropanation of 10 leads to an alkoxynorcarane 11, which on regioselective hydrolytic cleavage of the three-membered ring leads to the semiketal 12 as intermediate, and finally yields the a-methylated ketone 13 ... 

II. REGIOSELECTIVE REDUCTIVE CLEAVAGE OF CM3ENZYUDENE ACETALS TO BENZYL ETHERS... 

Regioselective electrophilic bromination of 7-methoxy-3-methylcarbazole followed by ether cleavage and introduction of the prenyl group in a nickel-mediated coupling reaction provides siamenol (five steps, 34 % overall yield) [75] (Scheme 15.22). 

Conversion of a 1,2- or 1,3-diol to the p-methoxyphenyl acetal (see below) followed by regioselective reductive cleavage of the acetal using diisobutylalane can be used for the differential protection of a 1,2- or 1,3-dioL. In the example shown in Scheme 4.198, two regioisomeric cleavage products were obtained (8 1) with the major p-methoxybenzyl ether being isolated in 72% yield.144 A related transformation has been applied to 3,4-dimethoxyphenyl acetals.365... 

A MOM ether can be introduced onto the more sterically hindered alcohol of a vicinal diol via the regioselective reductive cleavage of the intermediate ortho-ester prepared in situ from the diol and trimethyl orthoformate [Scheme 4.258].477 478 Regioselectivities of >30 1 are typical. 

O-demethylation of aryl methyl ethers of nonphenolic aporphine alkaloids. Regioselective demethylation by this method occurs at positions 1,8, and 11 of the aporphine nucleus methylenedioxy functions survive the reaction (447). Selective cleavage of the methylenedioxy group in O-methyl-bulbocapnine with boron trichloride is discussed in Section III,C (448). The ether cleavage of methoxy- and methylenedioxy-substituted isoquinoline has been reviewed (346). 

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