Alkoxides reaction with benzyl halides

Rhodium catalysts have also been used. Benzylic halides were converted to carboxylic esters with CO in the presence of a rhodium complex. In this case, the R could come from an ether R20, a borate ester B(OR )3, or an Al, Ti, or Zr alkoxide. Reaction with an a,co-diiodide, BU4NF and Mo(CO)e gave the corresponding lactone. ... 

Poly (ethylene oxide) macromonomers72 761 are made in a similar way, as the alkoxide end group is reactive enough towards benzylic halides. With methacryloyl chloride, side reactions are involved. It is better to first protonate the PEO, and then to have it react with methacryloyl chloride in the presence of some triethyl amine. One can also react co-hydroxy polyethylene oxide) with methacryloyl imidazole, or with methacrylic acid in the presence of dicyclohexyl carbodiimide (DCCf)77). 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

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... 

Benzyl chloride is an acceptable starting material, because the problem has specified that we must start with alkyl halides. However, we must still prepare the alkoxide anion. This is the conjugate base of cyclopentanol and can be made by the reaction of the alcohol with sodium metal ... 

This general method, consisting of the preparation of a sugar sodium salt of the alkoxide type and its reaction with a benzyl halide, usually in some inert solvent, has been employed many times. A number of methods have been utilized to prepare the sodium derivatives. Sodium metal with ether has been the reaction mixture most commonly employed, although dioxane has also been found satisfactory. 

Careful mechanistic studies on the carbonylation process have been reported by Yamamoto, including studies with isolated model compounds. - These studies have revealed several reaction pathways, and the particular pathway depends on whether the electrophile is an aryl or benzyl halide and whether the nucleophile is an amine or an alkoxide. The existing experimental data suggest that the latter pathway b in Scheme 17.29 involving insertion of CO into the palladium-aryl bond to form a benzoylpalladium halide intermediate occurs. These complexes have been isolated with PMe and PPhj as ligand and have been shown to form the ester product upon reaction with an alcohol and amine base and to form the amide products upon reaction with amine alone. 

Aldehydes rapidly, react with alkyl halides (e.e. ICH ) giving a mixture of products (15). This reaction has no synthetic utility, and was explained by a very fast Meerwein-Ponndorf reaction reaction at the level of intermediate secondary samarium alkoxides. This hypothesis was recently confirmed and gave rise to new developments for the catalyzed Op-penauer-Meerwein-Ponndorf-Verley reaction (see in IV). By taking very reactive halides (benzylic or allylic) it is possible to overcome the side-reaction and to get good yields of alcohols (23) (eq.p4j). 

One of the classic 8 2 reactions is the Williamson ether thesis (p. 315), the formation of an ether from an alkoxide and an alkyl halide. When an aldohexose is treated with benzyl chloride and potassium hydroxide, a series ofWilliamson ether syntheses results in formation of a tetraether and an acetal (Rg. 22.36). Be careful to notice the... 

This reaction, which is named after W. Williamson, is the most important method for the synthesis of unsymmetrical ethers 3. For this purpose an alkoxide or phenoxide 1 is reacted with an alkyl halide 2 (with R = alkyl, allyl or benzyl). Symmetrical ethers can of course also be prepared by this route, but are accessible by other routes as well. 

Reactions of organosamarium(II) halides with aldehydes are sranewhat more complicated and synthetically less useful than those with ketones. The ability of Sm species to serve as strong reducing agents introduces a number of alternative reaction pathways. For example, reaction of EtSmI with benzalde-hyde provides a mixture of benzyl alcohol, benzoin, hydrobenzoin, and benzyl benzoate in low yields. Die first three products presumably arise from benzaldehyde ketyl, generated by single-electron transfer from the Sm reagent to benzaldehyde. The benzyl benzoate apparently is derived frmn a Tischenko-type condensation reaction between a samarium alkoxide species and benzaldehyde. 

Ethers are frequently prepared via the Williamson ether synthesis, which involves the reaction of an alkyl halide electrophile (RX) with an alkoxide nucleophile (R O ). As usual, the Sn2 backside attack is sensitive to sterics, and the E2 elimination reaction is expected to compete here since alkoxides are strong bases. The Sn2 substitution can be expected to give good yields of the ether if the halide is on a methyl, primary, allylic, or benzylic carbon. Simple alkoxides may be commercially available otherwise, the alkoxide can be prepared from the corresponding alcohol by treatment with a strong base (NaH) or a metal (Na or K). 

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