Base‐Promoted Synthesis of N−H Free Pyrroles via net [3+2]‐Cycloaddition

Abstract

A base‐promoted net‐[3+2] cycloaddition of nitriles and 1‐arylpropynes for the synthesis of pyrroles is described. The developed method provides convenient access to various 2,5‐disubstituted or 2,4,5‐trisubstituted pyrroles in 40% to 96% yields (32 examples). Among methods for the synthesis of pyrroles, the protocol presented here stands out for its convenience and atom‐economy.

Masters of Mediation: MN(SiMe3)2 in Functionalization of C(sp3)−H Latent Nucleophiles

“…Considering the significant role of pyrroles in the field of medicinal chemistry, very recently Li, Walsh, Liang and coworkers developed a cost-effective and atom-economic synthesis of NÀ H free pyrroles 71 via net [3 + 2] cycloaddition of nitriles and 1-arylpropynes mediated by KN(SiMe 3 ) 2 (Scheme 33). [87] Efficiently, this protocol is also applied to the synthesis of 2,3,5-trisubstituted pyrroles. Here, they proposed a reaction pathway involving reversible deprotonation of 1arylpropyne 70, followed by nitrile addition resulting in metalated imine, which subsequently undergoing annulation to deliver the pyrrole.…”

Base-Promoted Synthesis of Isoquinolines through a Tandem Reaction of 2-Methyl-arylaldehydes and Nitriles

“…Some recent examples of our approach include the one-pot aminobenzylation of aldehydes with toluene derivatives (Scheme a) and a convergent synthesis of indoles from benzonitriles and fluorotoluenes (Scheme b) . We also introduced a series of tandem processes for the synthesis of more functionalized indoles, 3,4-dihydroisoquinolones, 2-azaaryl tetrahydroquinolines, and 2,5-disubstituted pyrroles involving the functionalization of benzylic or propargylic C–H bonds under basic conditions (Scheme c). Other impressive examples of the functionalization of toluene derivatives were developed by Kobayashi and co-workers, who introduced an asymmetric addition of toluene-derived benzyl groups to imines .…”