Synthesis of Disubstituted Pyrroles from
1,3-Dicarbonyls and Azides

Significance

The synthesis of a diverse range of 2,3-disubstituted pyrroles 4 is described from 1,3-dicarbonyl compounds 1 and 2-azido-1,1-dialkoxyethanes 2 via an intermolecular Staudinger-aza-Wittig reaction and subsequent cyclization. First, the required enamines 3 were prepared in good to excellent yield (>80% in most cases). Next, thorough optimization of the reaction conditions identified three distinct methods for cyclization to the desired pyrroles. In general, method A was used to prepare 3-acylpyrroles, whilst methods B and C were more successful for obtaining the ester-substituted pyrroles. The use of cyclohexane-1,3-diones as the dicarbonyl component leads to 6,7-dihydro-1H-indol-4(5H)-ones 7 in ­excellent yield over the two steps. Methods for conversion of 7 into the synthetically valuable 4-hydroxyindole are available.