TBHP‐Mediated Oxidative Decarboxylative Cyclization in Water: Direct and Sustainable Access to Anti‐malarial Polycyclic Fused Quinazolinones and Rutaecarpine

Abstract

of main observation and conclusion Polycyclic fused quinazolinones with anti-malarial activity were synthesized through tert-butyl hydroperoxide (TBHP)-mediated oxidative decarboxylative cyclization between commercially available isatins and cyclic amines in one step. The reaction proceeds smoothly in water without additional transition-metal catalyst, acid and base. The newly synthesized products were evaluated to exhibit moderate to good anti-malarial activity against chloroquine drug-sensitive Plasmodium falciparum 3D7 strain. Additionally, this method also provides direct approach to Rutaecarpine in good yield.

C1‐Functionalization of 1,2,3,4‐Tetrahydroisoquinolines (THIQs)

“…Recently, in 2020, Sun et al used isatins 88 as substrate in the reaction with THIQs 20 to produce the products 82 in moderate to good yields (59-86%) in the presence of TBHP in water at 100 °C (Scheme 18). [35] Initially, isatins 88 undergo the nucleophilic attack by TBHP and then the intramolecular rearrangement followed by the elimination of tertiary butanol to produce isatin anhydrides 89. On the other hand, THIQs 20 is converted to intermediates 90 through oxidation by TBHP or air as oxidant.…”

Lewis Acid‐catalyzed Tandem Synthesis of Quinazoline‐2,4‐diones by Reaction of Isatins with Aryl/Alkyl Amines using TBHP as Oxidant

“…Furthermore, this was also considered to be one of the most simple, clean, and multipurpose oxidant [17] . This was also promoted Baeyer‐Villiger type oxidation reactions [18–20] …”

“…[17] This was also promoted Baeyer-Villiger type oxidation reactions. [18][19][20] Lewis acid catalyzed transformations are more important in organic synthesis, among them Bismuth(III) salts, as representative green reagents and catalysts, have been extensively applied to the synthesis of natural products or significant pharmaceuticals. [21] Catalytic amount of Bi(III) salts is efficient in promoting different type of transformations like Claisen rearrangement, [22] epoxide opening, [23] Mukaiyama aldol reaction, [24] Mannich-type reactions.…”

Electrochemical [3+2] Cycloaddition of Anilines and 1,3‐Dicarbonyl Compounds: Construction of Multisubstituted Indoles

“…Our group has been engaged in the synthesis and screening of small molecules for the development of antimalarial drugs since the discovery of artemisinin by Tu. [18] Herein, we report an electrochemical approach for synthesizing multisubstituted indoles through the redox neutral cycloaddition of an aniline and a commercially available 1,3-dicarbonyl compound (Scheme 2c). The reaction could be performed under mild conditions without a transition-metal-catalyst or oxidant.…”