Synthesis of l,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and homologous pyridine and azepine analogues thereof

Abstract

Several syntheses of the previously unknown 1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid and various 5- and 6-substituted derivatives thereof have been devised. Some of these processes have been extended to the heretofore unreported 5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylic acid and 5,6,7,8-tetrahydro-9H-pyrrolo[1,2-a]azepine-9-carboxylic acid derivatives.Two new processes were developed for the conversion of pyrroles into the corresponding pyrrol-2-acetic acid esters. Both processes were based on the use of the readily available ethoxalylpyrrole derivatives as the starting material. One sequence involved saponification of the α-keto ester, followed by Wolff–Kishner reduction of the crude α-keto acid salt and subsequent esterification of the acetic acid derivative thus produced. The second synthesis commenced with reduction of the 2-ethoxalpyrrole with sodium borohydride to the α-hydroxy ester, which was further reduced to the acetic acid ester with an equimolar mixture of triphenylphosphine and triphenylphosphine diiodide.