Meerwein’s ester

A second example of the use of esters as enolates is the formation of Meerwein s ester, an intermediate in the synthesis of substituted adamantanes (6). Dimethyl... 

Meerwein s Ester (9) Dimethyl malonate (13.2 g, 0.4 mole) and 6 g of 40 % aqueous formaldehyde solution are mixed in an Erlenmeyer flask and cooled to 0° in an ice bath. To the mixture is added 0.3 g of piperidine and enough ethanol to produce a homogeneous solution. The solution is allowed to stand at 0° for 12 hours, at room temperature for 24 hours, and at 35 0° for 48 hours. The reaction product is washed with water (50 ml) followed by dilute sulfuric acid, then dried (sodium sulfate). Unreacted malonic ester is distilled off under vacuum leaving a residue of about 12.5 g, which contains methylenemalonic ester, methylenebismalonic ester, and hexacarbomethoxypentane. 

Bicyclof 3.3.1 ]nonane-2,6-dione (10) A solution of 10 g of Meerwein s ester, 30 ml of glacial acetic acid, and 20 ml of 6 A hydrochloric acid is heated under reflux for 10 hours. The solution is then carefully distilled under aspirator pressure until all volatile materials (water and acetic acid) are removed. The solid residue is distilled at 129-131°/4 mm to afford the product. It may be recrystallized from benzene giving about 3 g of bicyclo-[3.3.1]nonane-2,6-dione, mp 138-140°. 

The bc portion (267) was synthesized (Scheme 19) by treatment of the ethyl ester of i3, 3-dimethyllevulinic acid with hot ethanolic ammonia, followed by pyrolysis to give (275). Meanwhile, treatment of /8, 8-dimethyllevulinic acid with thionyl chloride gave the butyrolac-tone (276), and the sodium salt of this was treated with (275) to give (277). Photochemically induced acyl migration gave (278), which was treated with methanolic ammonia subsequent dehydration afforded (279), which was then activated by O- ethylation with Meerwein s salt to give (267). 

The cyanobromide (371) was condensed with the bc portion (347) to give the thioether (372) sulfide contraction to give (373) was accomplished using tris(/3-cyanoethyl) phosphine, and with phosphorus pentasulfide the thiolactam-thiolactone (374) was produced. After treatment with Meerwein s salt, reaction with dimethylamine opened the lactone with concomitant formation of an exocyclic methylene group, and subsequent treatment with cobalt chloride or iodide gave the chelate (375) which was reacted with diazabicyclononane to give bisnorcobyrinic add [Pg.435]

Protodesilylation, A new preparation of -unsaturated carboxylic acids involves the amide acetal Claisen rearrangement of a 3-(trimethylsilyl)allyl alcohol such as 1 to allylsilanes (2). Desilylation of 2 by usual methods results in formation of stereoisomers. However, use of liquid HF at low temperatures results only in (E)-3 in 88% yield. The HF-pyridine complex is not so stereoselective. Amides such as 3 can be converted into carboxylic acid esters by Meerwein s trialkyloxonium salts (—70% yield). 

A method has been described for the preparation of N-formyl-a-amino-acid t-butyl esters by formylation of the free base with a mixture of formic acid, DCC, and pyridine, thus overcoming the incompatibility of the t-butyl ester group with the usual acidic formylation conditions. The transfer hydrogenation technique has been recommended for the removal of N-benzyloxycarbonyl and benzyl ester groups from peptides. N-Acetyl-a-amino-acids are converted into the corresponding A-ethyl derivatives by reaction with Meerwein s reagent followed by reduction with sodium borohydride. ... 

Nitrones (192,193) may also be alkylated with Meerwein s reagent and dimethyl sulfate to give esters of N-alkoxyamino acids (207, 208) after hydrolysis 185) (Scheme 43). 

Media s. Solvents Medium, superacidic reactions in - 27,159 Meerwein s. Wagner Meisenheimer rearrangement, ring expansion by - 26, 151 Meldmn s acids s. Malonic acid esters, cyclic Mercaptals... 

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