Ethers, methyl allylic lithiation

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

The oxidative dimerization of the anion of methyl phenyl sulfone (from a Grignard reagent) in ethereal solution in the presence of cupric chloride in 5% yield has been reported47. Despite the reported48 poor stability of the a-sulfonyl C-centered radicals, Julia and coworkers49 provoked the dimerization (in 13 to 56% yields) of the lithiated carbanion of alkyl phenyl sulfones using cupric salts as oxidants. The best results are obtained with cupric triflates in THF-isobutyronitrile medium (56% yield for R = H). For allyl phenyl sulfones the coupling in the 3-3 mode is predominant. 

Formation of vinylic (trigonal C-Li), allylic or benzylic organolithiums a to O is more favourable. The useful acyl anion equivalent methoxyvinyllithium 11, for example, is formed on treatment of methyl vinyl ether with f-BuLi at -65 °C,13 and furan is lithiated by BuLi in Et20 at 0 °C to give 12.14 More complex carbohydrate-derived vinyl ethers such as 13 also lithiate readily.15... 

A, A, iV ,A -tetramethylethylenediamine (TMEDA) and A,A,A ,iV -tetramethyl-methylenediamine are treated with 5ec-butyllithium or tert-butyllithium. n-Butylpotassium converts dimethyl ether readily to methoxymethylpotassiumJ Ethyl and methyl vinyl ether require sec- or rm-butyllithium to undergo a-metalation, whereas n-butyllithium suffices to bring about the or// o-lithiation of anisole and the a-lithiation (at the oxygen-adjacent position) of allyl phenyl ether and benzyl phenyl ether. 

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