Carboxylation of γ-Butyrolactones with Methyl Methoxymagnesium Carbonate. New Synthesis of dl-Protolichesterinic Acid

The carboxylation of 7γlactones at the a position is, in most cases, easily accomplished by means of Stiles reagent (methyl methoxymagnesium carbonate). This combined with a simplified decarboxylative methylenation procedure, namely treatment of the α-carboxylactones with a mixture of formaldehyde and diethylamine, usually in a buffered acidic medium, affords a relatively simple method of synthesizing α-methylenelactones. These methods have been used in a new synthesis of dl-protolichesterinic acid. Free-radical addition of tetradecanal to dimethyl maleate led to methyl 3-methoxycarbonyl-4-oxoheptadecanoate, which was reduced by borohydride and cvclized to a 50:50 mixture of the methyl esters of c(s- and trares-3-carboxy-4-n-tridecylbutyrolactones, 20b (R = CH₃) and 20a (R = CH₃), respectively. Carbonylation of the acid from the latter isomer afforded 2,3-dicarboxy-4-n-tridecylbutyrolactone, which when treated with formaldehyde and diethylamine at room temperature afforded dl-protolichesterinic acid. Acylative decarboxylation of tricarballylic acid by tetradecanoic anhydride gives the di-γ-lactone of 3-(1,1-dihydroxytetradecyl)glutaric acid. The action of alkaline borohydride on the latter leads to trans-3-carboxymethyl-4-n-tridecylbutyrolactone (24, R = H). The methyl ester of this acid is also obtained almost exclusively when 20a (R = H) is subjected to an Arndt-Eistert homologation sequence. The cis acid 20b (R - H) on homologation gives varying mixtures containing both 24 (R = CH₃) and its cis isomer. The latter results together with other evidence allow the tentative assignment of stereochemistry to the carboxylactones 20a and 20b (R = H), the former being trans and the latter cis.