A Synthetic Methodology for Pyrroles from Nitrodienes

Abstract

Palladium complexes containing the ligand 4,7‐dimethoxy‐1,10‐phenanthroline have been used to catalyze the reductive cyclization of nitrodienes using carbon monoxide as the reductant to give pyrroles. Carbon dioxide was the only stoichiometric byproduct of the reaction. The yields were good and the starting materials can be easily synthesized in two steps by a cross‐aldol condensation reaction followed by a Henry reaction. Different substitution patterns are tolerated by this novel synthetic strategy.

Transition Metal Catalyzed Reductive Cyclization Reactions of Nitroarenes and Nitroalkenes

“…However, they are less reactive than nitroarenes and a competition experiment in which a nitroarene and a nitroalkene moieties were present on the same molecule resulted in the selective activation of the nitroaryl group. [23] Note that radical recombination appears to be fast for most if not all reactions described in this review. In the only two cases we are aware of in which a radical trap was added to the reaction mixture, [24][25] the yield of the cyclized product was not altered.…”

“…Nitroalkenes have a reduction potential of the same order of magnitude of that of nitroarenes and have recently been employed as substrates. However, they are less reactive than nitroarenes and a competition experiment in which a nitroarene and a nitroalkene moieties were present on the same molecule resulted in the selective activation of the nitroaryl group …”

“…Among the most useful ligands, 3,4,7,8‐tetramethyl‐phenanthroline has been employed in nitroarene cyclization reactions for many years . More recently, 4,7‐dimethoxy‐phenanthroline was found to give even better results . Phenanthrolines are easily displaced from palladium at high temperature and an excess of the ligands (typically from 2 fold to 16 fold) is always necessary to keep the catalytic system stable.…”

“…It should be noted that from the point of view of the heterocycles formed in the cyclization reaction, a successful cyclization of the quinole might have been considered as the first example of a metal‐catalyzed reductive cyclization of a nitrodiene by CO, a reaction unprecedented at the time and that requires a more donating phenanthroline, (MeO) 2 Phen, to be efficiently performed (see later) …”

“…Given the ability of nitroso groups to react with alkenes and the possibility of reducing nitroalkenes by CO, a logical extension of the reactivity described above is the cyclization reaction of conjugated nitrodienes. The reaction could indeed be performed by employing the same experimental conditions previously developed for the synthesis of thienopyrroles (Scheme ) …”