Carbanions alkyl benzyl ether

Reactions with Active Methylene Compounds. Enolates of ketones," esters," enediolates," 1,3-dicarbonyl compounds," amides and lactams," as well as nitrile-stabilized carbanions," can be alkylated with benzyl bromide. Cyclohexanone may be benzylated in 92% ee using a chiral amide base." Amide bases as well as alkoxides have been employed in the case of nitrile alkylations." Benzylation of metalloenamines may be achieved and enantioselective reactions are possible using a chiral imine (eq 3). However, reactions between benzyl bromide and enamines proceed in low yield. The benzylation of a ketone via its enol silyl ether, promoted by fluoride, has been observed. ... 

The rearrangement of an ether 1 when treated with a strong base, e.g. an organo-lithium compound RLi, to give an alcohol 3 via the intermediate a-metallated ether 2, is called the Wittig rearrangement. The product obtained is a secondary or tertiary alcohol. R R can be alkyl, aryl and vinyl. Especially suitable substrates are ethers where the intermediate carbanion can be stabilized by one of the substituents R R e.g. benzyl or allyl ethers. 

The above synthetic methods for oxetane all involve formation of a new C—O bond. Cyclization by formation of a new C—C bond has been applied with compounds having benzylic or alkylic CH groups. Recent examples of this type of ring closure are the rearrangement of trans- 2,3-epoxycyclohexyl allyl ether by means of s-butyllithium and the dehydrochlorination of a-cyanobenzyl 2-chloroethyl ether with aqueous base and phase transfer catalyst (equation 86). Both reactions probably involve carbanion intermediates (76TL2115, 75MIP51300). 

The great majority of experimental variants discussed for benzylation (see Sect. 2.1) has also been applied for the preparation of allyl ethers. Among them, the alkylation with allyl bromide and sodium hydride in a dipolar aprotic solvent is most frequently used for complete allylation. Reaction with the methylsulfinyl carbanion in DMSO to form an alkoxide, followed by the reaction with allyl bromide provides a convenient high-yield route to 2,3,6-tri-O-allyl-amylose [227], With the limited amount of reagent, 35% of methyl 2-0-allyl-3,6-dideoxy-a-D-xy/o-hexopyranoside was synthesized from the corresponding glycoside [228]. The 2-allyl ether was the major product (43 % yield) of the reaction of methyl 4,6-0-benzylidene-a-D-glucopyranoside with allyl bromide and 1.1 equiv. of sodium hydride in benzene [71]. 

The low yield of ortho lithiation, in the above experiments, is presumably due to the formation of the lithio salt of the alcohol in the first instance on treatment with the lithiating agent. Quite often the reaction becomes heterogeneous. A conceivable modification of the above reaction would be lithiation of the corresponding methyl ether derivative. However, in the latter case the reaction takes a different course. The chief reaction now is the formation of the benzylic carbanion which undergoes the Wittig rearrangement When the benzylic position is fully substituted by a carbon residue (such as alkyl or aryl), ortho lithiation occurs in better yield, and further reaction with COj furnishes the 3,3-disubstituted phthalides. 

Quinodimethanes have been employed in a stereoselective synthesis (ref. 128) of estrone. A silicon-stabilised benzylic carbanion was obtained, avoiding lithiation of the methoxy-substituted ring, from the intermediate [2-[(trimethylsilyl)methyl]-5-methoxybenzyl]dimethylamine and after alkylation with the requisite cyclopentano component, generation of the quinodimethane structure with CsF afforded racemic estrone methyl ether. 

Generation of the silicon stabilized benzyl carbanion 153 from 149 required the presence of hexamethylphosphotriamide. In its absence lithiation occurred at least in part in the aromatic ring. Alkylation of 153 with 152 produced 154 in 94% yield as a 2 1 isomer mixture at the benzylic site. Methiodide formation, addition of caesium fluoride, and refluxing in acetonitrile for 1.5 hours then afforded ( )-estrone methyl ether 28 (containing 7-8% of the C-9 p-H isomer) in 86% yield. Pure 28 was obtained on recrystallization. 

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. 

Applications Based on Deprotonation of Selenoketals R Se CHB — alkyl) and Seleno-orthoesters. Deprotonation, usually with KDA, of selenoketals (PhSe)2CHR (R = alkyl) gives carbanions that react efficiently with common electrophiles [primary alkyP - and benzyl halides, aldehydes, ketones, and (for R = alkyl or H) epoxides ]. A few of the resulting selenoketals have been hydrolysed under very mild conditions. Carbanions derived from selenoketals undergo intramolecular reactions [e.g. (49)] when appropriately substituted, and can be used in the synthesis of silyl enol ethers, e.g. (50). ... 

Alkylation of Carbanions. Methyl 2-phenylpropionate can be deprotonated with LDA and alkylated on carbon with benzyl chloromethyl ether. Introduction of the BOM group in both chiral amides (eq 5) and dianions (eq 6) gives good yields. Removal of the benzyl group by hydrogenolysis completes the hydroxymethylation process. 

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