Esters, sulfonate alkylation with alkoxides

When an alkoxide ion is used as the nucleophile, the reaction is called a Williamson ether synthesis. Because the basicity of an alkoxide ion is comparable to that of hydroxide ion, much of the discussion about the use of hydroxide as a nucleophile also applies here. Thus, alkoxide ions react by the SN2 mechanism and are subject to the usual Sn2 limitations. They give good yields with primary alkyl halides and sulfonate esters but are usually not used with secondary and tertiary substrates because elimination reactions predominate. 

Alkyl phenyl sulfones (piCj,27) are nearly as acidic as esters hence they are readily deprotonated by n-BuLi, LDA in THF, or EtMgBr in THF to give a-metalated sulfones. Their reaction with aldehydes gives a mixture of diastereomeric P-phenylsul-fone alkoxide adducts. Reductive elimination of the benzenesulfinate moiety from the adduct to produce the alkene is usually slow. To minimize side reactions, the hydroxyl group is first converted to an acetate, benzoate, mesylate, or /7-toluenesul-fonate and then treated with an excess of sodium amalgam [Na(Hg), prepared by adding small pieces of sodium to mercury] in methanol to furnish the trans-dlk n P... 

In Chapter 11, several different nucleophiles reacted with alkyl halides or sulfonate esters via both S l and Sn2 conditions. Alkoxides (RO ) are important nucleophiles, and the 8 2 reaction of an alkoxide with an alkyl halide was the basis of the Williamson ether synthesis in Chapter 11, Section 11.3.2. Based on the poor reactivity of tertiary halides with nucleophiles in the 8 2 reaction, reading Chapter 11 may lead to the conclusion that an alkoxide such as sodium ethoxide will give no reaction when mixed with a tertiary halide. This is incorrect. A reaction that forms the basis of this chapter occurs because alkoxides such as sodium ethoxide are strong bases as well as nucleophiles. 

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