Reaction between N-alkylpyrroles and alkyl-lithium reagents. The role of nitrogen substituent, solvent, alkyl-lithium, and complexing agents

Abstract

Six N-alkylpyrroles have been metallated with BuⁿLi under a variety of conditions. As the bulk of the nitrogen substituent increases, the total yield of lithiopyrroles decreases and the ratio of 2,4- to 2,5-disubstitution increases. Change of solvent from hexane to ethers generally accelerates metallation in the order hexane < diethyl ether < 2,5dimethyl-THF < 2-methyl-THF < THF, though this is accompanied by increased solvent cleavage, especially at elevated temperatures. Metallation is also accelerated by the addition of complexing agents, the order of effectiveness being NNN′N′-tetramethylethylenediamine > diazabicyclo[2.2.2]octane > tris(dimethylamino)phosphine > 1,4,8,11-tetramethyl-1,4,8,11-tetra-azacyclotetradecane. Change of lithiating agent from BuⁿLi to Bu^tLi leads to increased overall metallation.