Applying green chemistry principles to iron catalysis: mild and selective domino synthesis of pyrroles from nitroarenes

An efficient and general cascade synthesis of pyrroles from nitroarenes using an acid-tolerant homogeneous iron catalyst is presented. Initial (transfer) hydrogenation using the commercially available iron-Tetraphos catalyst is followed by acid catalysed Paal-Knorr condensation. Both formic acid and molecular hydrogen can be used as green reductants in this process. Particularly, under transfer hydrogenation conditions, the homogeneous catalyst shows remarkable reactivity at low temperatures, high functional group tolerance and excellent chemoselectivity transforming a wide variety of substrates. Compared to classical heterogeneous catalysts, this system presents complementing reactivity, showing none of the typical side reactions such as dehalogenation, debenzylation, arene or olefin hydrogenation. It thereby enhances the chemical toolbox in terms of orthogonal reactivity. The methodology was successfully applied to the late-stage modification of multi-functional drug(-like) molecules as well as to the one-pot synthesis of the bioactive agent BM-635.

Automated summary

An efficient and general cascade synthesis of pyrroles from nitroarenes using an acid-tolerant homogeneous iron catalyst is presented. The method involves initial (transfer) hydrogenation using an iron-Tetraphos catalyst and subsequent acid catalysed Paal-Knorr condensation. It shows high functional group tolerance, complementing reactivity, and enhanced chemoselectivity.