Base-Mediated Direct Transformation of N-Propargylamines into 2,3,5-Trisubstituted 1H-Pyrroles

Abstract

An efficient and base-mediated intramolecular cyclization of N-propargylamines for the synthesis of structurally diversified pyrroles in high yield has been described. The developed methodology is broadly applicable and is tolerated by a variety of functional groups. Key intermediates of natural product discoipyrrole C as well as HMG-CoA-reductase inhibitor have been successfully synthesized using developed chemistry. The proposed mechanism was supported by control experiments.

Superbase‐Promoted N‐α‐sp3C‐H Functionalization of Tertiary Enaminones: Synthesis of Polysubstituted Pyrroles

“…On the basis of the aforementioned observations and previous reports, a tentative mechanism for this reaction was proposed, as depicted in Scheme . Initially, the superbase‐promoted abstraction of the benzylic proton from tertiary enaminone 1 generates the anion A , which is stabilized by an aromatic ring (R 4 ).…”

“…In this aspect, Cui reported a KO t Bu/DMSO promoted N ‐α‐sp 3 C−H functionalization of enaminones for the synthesis of substituted pyridines in 2015 (Scheme , b) . Recently, Verma reported a KOH/DMSO mediated N ‐α‐sp 3 C−H functionalization of N ‐propargylamines for the synthesis of pyrroles (Scheme , c) . In our continuing interest in heterocycle synthesis, we herein report an efficient superbase‐promoted N ‐α‐sp 3 C−H functionalization of tertiary enaminones for the regiospecific synthesis of substituted pyrroles (Scheme , d).…”

K2S2O8-Mediated Synthesis of Highly Functionalized Pyrroles via Oxidative Self-Dimerization of N-Propargylamines

“…The ease of preparation of N -propargylamines from aldehydes, amines, and alkynes via A 3 -coupling is adding to their importance in organic synthesis as synthetic precursors due to their ability to form various nitrogen heterocyclic compounds. Although a number of methods for the synthesis of nitrogen heterocycles have been reported in the literature, synthesis of functionalized pyrroles directly from N -propargylamines is limited . In recent years, radical reactions have attracted broad attention in organic synthesis and have been widely applied in medicinal and materials chemistry.…”

“…On the other hand, silver catalyzed oxidative transformation with K 2 S 2 O 8 have been widely used for the C–H bond functionalization to form C–C, C–N, C–S, and C–P bonds . Although N -propargylamines have been used for the synthesis of pyrroles with other coupling partners, radical mediated direct transformations of N -propargylamines into pyrroles without a coupling partner have not been reported yet. Keeping these challenges in mind, herein, in this article, we have demonstrated a radical initiated direct transformation of N -propargylamines into 1,2,3,4,5-pentasubstituted pyrroles having two carbonyl groups in the side chain catalyzed by AgOBz in the presence of K 2 S 2 O 8 .…”

Synthesis of 2,2,5-Trisubstituted 2H-Pyrroles and 2,3,5-Trisubstituted 1H-Pyrroles by Ligand-Controlled Site-Selective Dearomative C2-Arylation and Direct C3-Arylation

“…On the basis of these results, we chose JohnPhos for C2-selective dearomative arylation and tBuBrettPhos for C3-selective direct arylation. Direct C3-arylation of 1H-pyrrole 6d,12 is an attractive approach for the rapid preparation of multisubstituted 1H-pyrroles, and this report presents the first examples for the site-selective direct C−H arylative preparation of 2,3,5-triaryl-1H-pyrroles 13 from 2,5-diaryl-1H-pyrroles.…”