Aminomethylated Pyrroles: Casting a Spotlight

The chemistry and applications of aminomethylated pyrroles are extensively reported by the present review. An overall account of the synthetic approaches to pyrrole Mannich bases is offered, with an emphasis on topics such as regioselectivity (α-aminomethylation over α-aminomethylation, C-Mannich reaction versus N-Mannich reaction), mono- and bis-aminomethylation, influence of substituents in the pyrrole ring, chemoselectivity, or the special mention of N-tert-butoxycarbonyl-2-[(tert-butyldimethylsilyl)oxy]pyrrole as a substrate. The scope and limitations of the aldehyde component and amine reagents in the Mannich reaction of pyrroles have been explored, the use of preformed aminomethylation reagents and catalysts with the view to improve yields or stereoselectivity has been surveyed, and the mechanism and by-products arising from the aminomethylation of pyrroles have been outlined. Pyrrole Mannich bases have been portrayed as excellent H-, C-, N-, O-, S-, and P-alkylating agents as a direct consequence of their ability to replace the easily leaving dialkylamino group with other nucleophiles, and the involvment in ring closure processes leading to porphyrins, or other miscellaneous reactions have also been included in the broad coverage of these compounds' reactivity. A particular attention has been paid to the contribution of pyrrole Mannich bases to drug discovery and advances in medicinal chemistry.