Bromide benzyl, reaction with alkoxides

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]. 

Benzyl ethers are widely used and an example has already been seen in Section 3.5.3 in the description of the synthesis of methyl tri-O-benzyl-a-L-fucopyranoside 3.36. Most often benzylation is carried out in an alkaline medium. Oxolane can be employed as solvent, but the reaction is much faster in N.N-dimethylformamide (DMF), a better solvent for only partially protected sugars. As base, KOH has been used but now the preferred method is to make alkoxides with a very slight excess of NaH. The alkylating reagent is benzyl bromide. Benzyl ethers are stable under moderate acidic conditions and in an alkaline medium. In a general fashion, benzyl ethers are cleaved by catalytic hydrogenation according to equation (5.1). 

Alcohols and phenols are benzylated upon treatment with benzyl bromide under basic conditions. For example, treatment of alcohols with Sodium Hydride or Potassium Hydride in ethereal solvent or DMF generates alkoxides, which subsequently undergo Williamson reactions with benzyl bromide. Selective benzylation of a primary alcohol in the presence of a secondary alcohol has been accomplished in DMF at low temperature. ... 

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 Pd-catalysed intermolecular reaction of aryl bromides containing electron-withdrawing substituents with a wide variety of alcohols including MeOH, 2-propanol, benzyl alcohol and i-butyl alcohol gives the aryl ethers 416 under milder conditions than uncatalysed reactions. Bidentate ligands such as BINAP and DPPF (XLIX) are effective [206,207]. The aryl Pd alkoxide 417 was isolated as an intermediate, and the formation of the aryl ethers 418 by reductive elimination of 417 was confirmed. 

Having successfully assembled the desired tetracyclic system, examination of corresponding tricyclic systems derived from synthetic precursor 259 were relatively straightforward. Smooth access to lipophilic methyl and benzyl ethers 262 and 263, respectively, was accomplished via Sn2 reaction of the sodium alkoxide, derived from alcohol 259 and NaH with either methyl iodide or benzyl bromide (Scheme 23). 

The method is an extension of the well-known Grignard synthesis in ethers to the use of nonsolvating media, and is a development of procedures previously reported.2-6 A version of it has been employed with straight-chain primary alkyl chlorides, bromides, and iodides from C2 to Cu,5-7 and in solvents (or an excess of the halide) which permit reaction temperatures above 120°, with simple aryl halides such as chlorobenzene and 1-chloro-naphthalene. Branched-chain primary, secondary, and tertiary alkyl halides, allyl, vinyl, and benzyl halides either fail to react or give extensive side reactions. Better results are reported to be obtained in such cases with the use of catalytic quantities of a mixture of an alkoxide and an ether such as diethyl ether or tetrahydrofuran in a hydrocarbon medium, but the products are not, of course, completely unsolvated.4... 

Tributylstannyl ethers are covalent derivatives with the nucleophilic properties of soft metal alkoxides they react with benzyl bromide on heating in non-polar solvents in the presence of tetraalkylammonium bromides or iodides to give the O-benzyl ether [Scheme 4.166]. 309 310 The moisture sensitive tributylstannyl ethers are formed by reaction of an alcohol with bis(tributyltin) oxide (bp... 

Preparation.—Ethers. A new method for benzylation of hindered glucidic hydroxy groups e.g. 73) requires reaction of the alkoxide with benzyl bromide and a catalytic quantity of a quaternary ammonium salt, and it is suggested that weakened ion-pairing might account for the increased efficiency. A simple, high yield, methy-lenation of catechols with dihalomethanes, in the absence of the usual strong... 

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