Facile Chemodivergent Synthesis of Fused Indolo[2,3- b ]quinoxalines and Benzo[4,5]imidazo[1,2- c ]quinazolin-6(5 H )-ones: An Organocatalytic Trifluoromethanesulfonic Acid-Controlled Mechanistic Switch between Condensation and Ring Expansion of the Isatin Core
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide A mild metal-free chemodivergent synthesis leading to products of two different chemotypes, such as indolo[2,3- b ]quinoxalines and benzo[4,5]imidazo[1,2- c ]quinazolin-6(5 H )-ones, has been described from common starting materials, isatin and 1,2-diaminobenzene, at room temperature in an environmentally benign EtOH solvent. The EtOH mediated condensation between isatin and 1,2-diaminobenzene delivers exclusively fused indolo[2,3- b ]quinoxalines in good/excellent yields (65–89%) in 8 h, and catalytic protic acid (CF 3 SO 3 H) in EtOH furnishes N-fused benzo[4,5]imidazo[1,2- c ]quinazolin-6(5 H )-ones selectively in good/excellent yields (66–88%) in 2 h via rearrangement of the isatin core following C2–C3 bond cleavage and N-atom insertion with 1,2-diaminobenzene. Thus, the switch selectivity between benzo[4,5]imidazo[1,2- c ]quinazolin-6(5 H )-ones and indolo[2,3- b ]quinoxalines could be finely programmed with the presence/absence of catalytic CF 3 SO 3 H induced by an ionic vs non-ionic pathway. A wide array of starting materials housing structural and electronic variations (e.g., electronically neutral, moderate/strong electron-donating, moderate electron-attracting functionalities, and heteroarene) allows the scope of diversity creation and provides facile access to molecular libraries with elaborate, well-decorated structures. The operational simplicity, ease of product purification (in the case of indolo[2,3- b ]quinoxalines) by precipitation/filtration, recyclability of catalytic CF 3 SO 3 H, and a high degree of chemoselectivity through decisive cleavage of the C2–C3 bond over other labile bonds under protic acid catalysis signify distinct advantages of developed protocols. The late-stage synthetic manipulation at the free-NH site of final products and a “gram-scale” preparation further demonstrate the promising usefulness of chemodivergent synthesis.
Source: ACS Omega
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,935
OpenAlex ID: W4417440979