Carboxylic esters demethylation

Thiolate ions are also useful for the demethylation of certain ethers, esters, amines, and quaternary ammonium salts. Aryl methyl ethers can be cleaved by heating with EtS in the dipolar aprotic solvent DMF ROAr + EtS ArO +EtSR. Carboxylic esters and lactones are cleaved (the lactones give co-alkylthio carboxylic acids) with a thiol and AICI3 or AlBrs. Esters and lactones... 

Magnesium or lithium enolates of thiol carboxylic esters can be acylated with suitable reagents (c/ Volume 2, Part 1). Highly functionalized new derivatives are obtained. The example shown in equation (35)33,102 J5 closely related to the C-acylation of malonyl-CoA with acetyl-CoA, which plays an important role in the biosynthesis of polypeptides and fatty acids. (S)-4-Hydroxy-5-methyl-3-oxo-hexanoyl-L-leucine esters (41), 2-demethyl analogs of the Hip-Leu moiety of didemnin antibiotics, can be prepared via the 3-keto thiol carboxylic esters (40 equation 36). ° ... 

Ester hydrolysis.1 Pyridinium chloride selectively demethylates methyl esters of o-substituted aromatic carboxylic acids. 

The second route to ipalbidine also provides the first synthesis of its /5-d-glucoside ipalbine.3 2-Methoxypyrroline (4) was condensed with methyl acetoacetate at 85 °C in the absence of solvent to give the keto-ester (5). Acylation of the sodium salt of (5) was achieved with p-methoxyphenylacetyl chloride, but the expected acyl derivative could not be isolated. However, after the addition of a further equivalent of sodium hydride and heating at 80 °C the cyclization product (6) was obtained in moderately good yield. Some of the corresponding carboxylic acid was also isolated. Demethylation and decarboxylation of (6) by means of 48 % hydrobromic acid then gave the tetrasubstituted pyridone (7), which was... 

The short duration of action of meperidine is the result of rapid metabolism. Plasma esterases cleave the ester bond to leave the inactive zwitterionic 4-carboxylate derivative. Meperidine also undergoes N-demethylation to give normeperidine. Normeperidine has little analgesic activity, but it contributes significantly to the toxicity of meperidine. 

More recently, Tada and co-workers reported the total synthesis of patulin (348) in 1994 (Scheme 7.1) (507). Starting with the condensation of acetonedicarboxylic acid dimethyl ester (353) and chloroacetaldehyde to form an appropriately 2,3-disubstituted furan 354, this was further reduced and selectively oxidized at the aromatic carbinol to deliver 3-furaldehyde 355. Dean-Stark condensation of this species in the presence of methanol gave the methyloxy furanopyran 356. Oxidative ring-opening to a carboxylate intermediate and subsequent methylation with diazomethane provided ester 357, which was lactonized and finally demethylated to deliver the natural product 348 in 7% yield over a total of eight consecutive steps. 

Deprotection of Derivatives of Carboxylic Acids.—Methyl esters are demethylated with anhydrous trifluoroacetic acid, in yields ranging from quantitative to 2%. Triarylamine radical cations react with benzyl esters in an oxidative cleavage reaction to give carboxylic acids yields are best with p-methoxybenzyl esters. ... 

A final synthetic effort in the yohimbine alkaloid area concerns the studies reported by Loewenthal and his coworkers (Scheme 3.92) (143). The aim was to develop an efficient method to prepare the bicyclic enone 21, which serves as a key intermediate in the Woodward reserpine synthesis strategy (19). The route for preparation of 21 began with Friedel Crafts reaction of 2-methoxynaphthalene (523) with the oxalyl chloride equivalent 524, a process which afforded the acenaphthenoquinone 525. Oxidative-decarboxylation of 525 yielded the naphthalene-carboxylic acid 526 which was transformed by Birch reduction and esterification to the dihydro-derivative 527. Carboxyla-tion then provided geminal diester 528 which was epoxidized. Sequential lactonization and methylation afforded tricyclic lactone 529. Ester cleavage with subsequent decarboxylation gave lactone 530 which was demethylated to provide 531. While no further effort was given to the development of this... 

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