The protecting–directing role of the trityl group in syntheses of pyrrole derivatives: efficient preparations of 1-H-pyrrole-3-carboxylic acid and 3-acyl-, 3-amino-, and 3-bromo-1-tritylpyrroles

Abstract

Trifluoroacetylation, formylation, and bromination of 1-tritylpyrrole occur regioselectively at the 3-position in high yields. Quantitative hydrolysis of the 3-trifluoroacetyl derivative and removal of the trityl group from the resulting acid with sodium in liquid ammonia furnishes a new, short, high-yielding synthesis of the simple 1-H-pyrrole-3-carboxylic acid. 1-Tritylpyrrole-3-carboxylic acid has been converted efficiently into 3-aminopyrroles via Curtius rearrangement of the derived azide: 3-amino-1-tritylpyrrole appears to exist in solution exclusively as its imino-Δ⁴-pyrroline tautomer. 1-H-3-t-Butyloxycarbonylaminopyrrole undergoes trifluoroacetylation regioselectively at the 2-position. Metallation of 1-tritylpyrrole with butyl-lithium in hexamethylphosphoric triamide gives rise to the unexpected products 9-phenylfluorene, 1-methoxycarbonylpyrrole and methyl triphenylmethylacetate (after work-up of the lithiointermediates with carbon dioxide and methylation of the resulting acids).

The mechanism proposed for the reductive cleavage of the trityl group in 1-tritylpyrrole is supported by the results of cyclic voltammetry experiments.