Rapid Access to Novel 1,2,3-Triazolo-Heterocyclic Scaffolds via Tandem Knoevenagel Condensation/Azide–Alkyne 1,3-Dipolar Cycloaddition Reaction in One Pot

Abstract

An operationally simple, one-pot, two-step cascade method has been developed to afford biologically important fused 1,2,3-triazolo-heterocyclic scaffolds from 2-alkynyl aryl(heteroaryl) aldehydes and phenacyl azides. This unique atom economical transformation engages four reactive centers (aldehyde, alkyne, active methylene, and azide) under metal-free catalysis.

New click-chemistry methods for 1,2,3-triazoles synthesis: recent advances and applications

“…A tandem one-pot Knoevenagel/azide-alkyne cycloaddition reaction between indole, pyrazole or aryl containing aldehydes and phenylazide were successfully conducted in the presence of piperidinium acetate in methanol (scheme 2). 20 Scheme 2: tandem one pot Knoevenagel/azide-alkyne cycloaddition reaction using an indole aldehyde.…”

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…The mechanistic pathway was proposed in accordance with the experimental evidences and literature reports (Scheme 331). [330][331][332] Recently in 2020, Devi et al reported an indium (III) chloride-catalyzed intramolecular Friedel-Crafts cyclization reaction of N-tethered benzyl-alkenol 571 towards the synthesis of 4-vinyl-1,2,3,4-tetrahydroisoquinoline 572 in good yields (Scheme 332). [333] Zhang et al disclosed an electrochemical intramolecular CÀ H/NÀ H functionalization of N-((4-arylbut-3-yn-1-yl)oxy)benzamide 573 towards the synthesis of isoxazolidine-fused isoquinolin-1(2H)-ones 574 (Scheme 333).…”

“…The mechanistic pathway was proposed in accordance with the experimental evidences and literature reports (Scheme 331). [330–332] …”

Role of Click Chemistry in Organic Synthesis

“…Additional aromatization by DDQ gave fused heterocyclic scaffolds (32) (Figure 19 Method 2). In the subsequent year, a one-pot tandem, Knoevenagel/azide-alkyne cycloaddition reaction between indole, aromatic aldehydes or pyrazole and phenylazide was fruitfully accomplished in the presence of piperidinium acetate in methanol to furnish the desired triazole derivatives (33) (Figure 19 Method 3) [60].…”