Base‐Promoted Synthesis of Polysubstituted 4‐Aminoquinolines from Ynones and 2‐Aminobenzonitriles under Transition‐Metal‐Free Conditions

Abstract

A transition-metal-free and base-promoted one-pot reaction of ynones with 2-aminobenzonitriles is described. The reaction was initiated through sequential aza-Michael addition/intramolecular annulation to afford various multisubstituted 4aminoquinolines and 4-amino-1,8-naphthyridines in good to excellent yields. Operational simplicity, high atom-economy with broad substrate scope makes this protocol more attractive. Also, the gramscale synthesis and further transformation of the product were studied. Additionally, 2-haloarylyones as substrate provide N-arylquinolones as the sole product via the S N Ar mechanism.

Recent Advances in Green Synthesis of Functionalized Quinolines of Medicinal Impact (2018‐Present)

“…In year 2021, Kumar et al proposed a metal free, base assisted synthesis of polysubstituted Amino-quinolines 164 (Scheme 44). [84] The reaction was performed between 2-amino benzonitrile compounds 162 and ynones 163 in DMSO using base potassium tert-butoxide following Aza-Michael annulation. The highlights of this reaction are wide substrate scope including aromatic or heterocyclic moieties and ease of operation with better yields of products.…”

Base-mediated ynone-isocyanide [3+2] cycloaddition: a general method to 2,3,4-tri-substituted 1-H-pyrroles and bis-pyrroles

“…Ynones and isocyanides have emerged as excellent precursors for the construction of a variety of heterocycles via cycloaddition reaction. 13 In continuation of our recently developed method for the synthesis of 4-aminoquinolines and 4-aminonaphthyridines from ynones using super-basic conditions, 14 d we hypothesized that the direct synthesis of functionalized NH-pyrroles 3 and bis-pyrroles 5 could be achieved in one-pot by the reaction of ynones 1 with tosyl-substituted isonitriles 2 (Scheme 1c).…”

Pd(II)-Catalyzed Three-Component Synthesis of Furo[2,3-d]pyrimidines from β-Ketodinitriles, Boronic Acids, and Aldehydes

“…This methodology was equally successful when the phenyl ring of (1) was replaced with benzo [d][1,3]dioxole (10) and naphthyl (11) units, giving their respective furo-pyrimidine (10aa′, 55%; 11aa′, 74%). Unfortunately, the β-ketodinitriles having a thiophene (12) and tetralone (13) failed to give the corresponding products (12aa′, 0%; 13aa′, 0%). This is possibly due to their competitive metal binding with the catalysts, making it difficult to participate in the carbopalladation/migration process.…”

“…As one can see from the X-ray diffraction (XRD) structure of one of its derivatives [ 1ea′ (Scheme )], the C-2 phenyl ring where the annulation is taking place is in the same plane, whereas the other phenyl (C-4) is out of the plane. In addition, p -Br-substituted furo-pyrimidine 8aa′ undergoes Pd­(II)-catalyzed Suzuki coupling with phenylboronic acid a and Heck coupling with 4-methylstyrene z , giving the corresponding cross-coupled products ( 8y , 80%; 8z , 82%).…”