Ether, benzyl methyl deprotonation

Tricarbonylchromium-complexed benzyl methyl ether was deprotonated using (eri-butvllithi-um and alkylated at the benzylic position without any Wittig rearrangement1. 

In polar solvents the excited state of sufficiently electron deficient arenes will accept an electron from donors. The fates of the radical ion pairs produced include formation of products of addition to the arene ring. A new example of this mode of reactivity is the photochemical reaction of 1,4-dicyanonaphthalene with benzyl methyl ether in acetonitrile. This yields stereoisomers of the addition product (120). The reaction most likely involves electron transfer from the ether to the naphthalene excited state and subsequent ionisation of a proton from the benzyl ether radical cation. This produces a benzyl ether radical which adds to the naphthalene derivative. An analogous sequence is proposed to explain the photochemical formation of (121)-(124) from ultra-violet light irradiated solutions of naphthalene-1,2-dicarboxylic acid anhydride in methanolic benzene or acetonitrile containing isobutene, 2-butene or 2-methyl-2-butene. Here it is suggested that the alkene radical cation, formed by electron transfer to the excited state of the naphthalene, is attacked by methanol deprotonation... 

Subsequent studies by Wittig demonstrated that deprotonation of benzyl alkyl ether derivatives with phenyllithium could provide the requisite carbanion and induce [1,2]-Wittig rearrangement. For example, treatment of benzyl methyl ether (9) with phenyllithium provided a-methyl benzyl alcohol (10) in 35% yield upon workup. 

Stevens rearrangements proceed smoothly whenever a benzylic group is migrating. For example, ethereal phenyllithium readily deprotonates tetramethylammon-ium bromide to give the lithium bromide-complexed ylide. This species reacts with a variety of electrophiles such as benzophenone, methyl iodide, or molecular iodine. But when the suspension is shaken in a sealed tube for 90 h at ambient temperature, the ylide decomposes entirely to trimethylamine and polymethylene (up to 74%) irrespective of the solvent used (DEE, THE, glyme). The same kind of degradation occurs when phenyllithium is replaced by -butyllithium or phenylsodium. ... 

The enantiomerically pure l-[(benzyl(dimethyl)silyl)methyl]pyrrolidine, obtained from ben-zyl(chloro)(dimethyl)silane and (5,)-2-(methoxymethyl)pyrrolidine , afforded after deprotonation and subsequent alkylation the diastereomerically pure (by NMR spectroscopy) (a-alkylben-zyl)silanes2. To obtain this high degree of diastereoselectivity, the alkylation had to be performed in the weakly complexing solvent diethyl ether. In THF a diastereomeric ratio of only 3 1 was found with iodomethane as alkylating agent. 

Benzylic deprotonation is often an inefficient process. It may be more important than it would appear from the end products, however, since radical cation deprotonation followed by reduction of the radical and reprotonation may regenerate the starting material. This mechanism has been proposed to explain the inefficiency of some PET alkylations [68]. In suitable models such a process has been revealed, e.g. deuterium incorporation at the bis-benzylic position in 2-(4-methoxyphenyl)-2-phenylethyl methyl ether and cis-trans isomerization in 2-methoxy-l-(4-methoxyphenyl)indane (but not in the corresponding 3-methoxyphenyl derivatives) [204], as well as deconjugation of 1-phenylalkenes to 3-phenylalkenes in the presence of 1,4-dieyanobenzene, biphenyl (as a secondary donor) and a hindered pyridine as the base [205]. Deprotonation of N,N-dimethylaniline has likewise been observed (Scheme 38) [206-207],... 

Examples of benzylic alkylation, aromatic ring deprotonation, and nucleophilic addition to a -position were used in a synthesis of (+)-20-methoxy-serrulat-14-en-7,8-diol. Deprotonation of the optically active complex (54) followed by reaction with chloromethyl methyl ether affords (55)... 

Enders and Jegelka [88] have used l,3-dioxan-5-one 122, a protected dihydroxyacetone derivative, to construct enantiomerically pure C5- to C9-deoxycarbohydrates. For example, reaction of 122 with SAMP gives the hydrazone 123, which is deprotonated and alkylated with methyl iodide to yield 124. The monoalkylated hydrazone is then alkylated in the same manner with chloromethyl benzyl ether to form 125. Cleavage of the hydrazone with ozone furnishes the protected ulose 126 (>98% de, >98% ee), which is deprotected to (—)-5-deoxy-L-r/ir o-3-pentulose 127. Reduction of 126 with L-Selectride, followed by deprotection, provides 5-deoxy-D-arabinitol 128 (>95% de, >95% ee) (Scheme 13.46). 

The 4-hydroxyl of 8,9-0-isopropylidene derivative 4b has been protected as its 4-t-butyl-dimethyl-silyl ether 4e. Then, the 7-hydroxyl has been converted to its xantate ester 4f, by deprotonation with butyl litium, treatment with carbon disulfide and alkylation with methyl iodide. Deoxygenatiobn of the 7-position has been accomplished by heating with tributyl-tin hydride in xylenes. Then, the cleavage of acetonide and of silyl ether, by heating in 80% acetic acid, followed by hydrogenolysis to remove the benzyl ester, afford 7-deoxy-Neu%Ac-ctMe Im. 

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