O-Methylpodocarpic acid

Cleavage hindered esters. Hindered esters can be cleaved efficiently by treatment with boron trichloride in methylene chloride. Thus methyl O-methylpodocarpate (1) is cleaved by the reagent at 0° to the corresponding acid, O-methylpodocarpic acid. 

Cleavage of methyl esters.1 The reagent (in HMPT) is very effective for cleavage of methyl esters under mild conditions. Thus the very hindered methyl mesitoate is cleaved to the acid in quantitative yield at 25° (1.25 hours). Methyl O-methylpodocarpate (1) is readily cleaved to O-methylpodocarpic acid in quantitative yield at 25° (1.5 hours). This reaction had been effected previously with potassium /-butoxide in DMSO, but required 2 hours at 52°.2 Bartlett and Johnson also examined the selective ester cleavage of methyl 3/3-acetoxy-A5-etienate (2). 

The synthesis of methyl D-podocarpate (3) is typical of the transformations that can be carried out with Mn(OAc)3. Oxidation of 1 with 2 equivalents of Mn(OAc)3 in AcOH at 15 °C afforded 50% of 2 as a single isomer that has been converted to methyl 0-methylpodocarpate by Clemmensen reduction (26). Both enantiomers of O-methylpodocarpic acid have been prepared using the appropriate phenylmenthyl ester (49). 

A soln. of BCI3 in methylene chloride added at -25° to a soln. of methyl O-methylpodocarpate in the same solvent, and allowed to stand 5-6 hrs. at 0° -> O-methylpodocarpic acid. Y 90%. - No cleavage of the methyl ether function occurred under the above conditions. P. S. Manchand, Chem. Commun. 1971, 667. 

Oxidation of unsaturated keto esters affords a-keto radicals which add to alkenes to give alkyl radicals which are oxidized to alkenes in the presence of Cu(OAc)2. If the alkyl radical is a 4-phenylbutyl radical, cyclization onto the aromatic ring results in the formation of a tetralin. This reaction occurs stereospecifically, as shown in the synthesis of O-methylpodocarpic acid (eq 7). ... 

Almost 2 equivalents H2O2 and coned. HCl added at 5-10° to a soln. of the startg. m. in acetic acid, and kept overnight at the same temp. -> methyl 6-chloro-ll-nitro-7-oxo-O-methylpodocarpate. Y 80%. F. e. s. B. Kumar and S. Kalra, J. Indian Chem. Soc. 50, 613 (1973) with metal halides in place of HCl, a-balogeno-carbonyl compds., cf. N. Inukai et al., Chem. Pharm. Bull. 24, 820 (1976). 

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