Pyrrole Studies XXVII.1 Utilisation of 1-Methyl-2-pyrrolyl Lithium in the Synthesis of 1-Methyl-2-substituted Pyrroles

Abstract Although metallation of 1-substituted pyrroles with alkyl lithium reagents to give the lithiated derivatives has been recorded by several research groups,4–6 only limited use has been made of these derivatives in the synthesis of 1,2-disubstituted pyrroles. Subsequent to ourinitial studies,7 it was reported that tetrahydrofuran was the solvent of choice for the formation of the mono-lithiated pyrrole derivative and that the rate of the metallation was accelerated by the presence of TMEDA.6 We had noted,7 however, that prolonged reaction of n-butyl lithium with 1-methylpyrrole in a 2:1 mixture of tetrahydrofuran:hexaneat ca 18°C in the absence of TMEDA gave 1-methyl-2-pyrrolyl lithium in yields in excess of 85%, as confirmed by the reaction of the lithiated derivative with D20 to give a deuterated pyrrole, the mass spectrum of which showed the incorporation of only one deuteriumatom. 1H and 13 C n.m.r. data also identified the product to be the 2-lithiated derivative to the exclusion of dilithiate...