Methanol → (1R,4S)-rel-4-(Acetylamino)-2-cyclopentene-1-carboxylic Acid Methyl Ester

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The recent description of an unequivocal route to 2-azabicyclo[2.2.1]hept-5-en-3-one (1, referring to the corresponding number on the flow sheet) (Jagt et al, J. Org. Chem., 39, 564 (1974)) offers a unique starting point for the synthesis of carbocyclic aminonucleosides of known geometric configuration. Acidic hydrolysis of this compound to cis-4-aminocyclopent-2-ene carboxylic acid hydrochloride, followed by esterification of the carboxyl function in refluxing methanol and subsequent acetylation of the amino group in acetic anhydride-pyridine, gives methyl(+)-cis-4-acetamidocyclopent-2-ene carboxylate (2). Reduction of the methyl ester of 2 gives, after acetylation, acetate 3. Epoxidation of acetate 3 is stereoselective due to the syn-directing allylic amide group, giving only the cis-epoxide 4. Hydrolysis of the easily synthesized epoxide 4 and subsequent acetylation gives a mixture of 5, 6 and 6a.

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