Tandem Synthesis of Pyrroloacridones via [3 + 2] Alkyne Annulation/Ring-Opening with Concomitant Intramolecular Aldol Condensation

• Published in: Journal of organic chemistry Vol. 78; no. 11; pp. 5372 - 5384
• Main Authors: Verma, Akhilesh K, Kotla, Siva K. Reddy, Aggarwal, Trapti, Kumar, Sonu, Nimesh, Hemlata, Tiwari, Rakesh K
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.06.2013; Amer Chemical Soc
• Subjects: Acridines - chemical synthesis; Acridines - chemistry; Aldehydes - chemistry; Alkynes - chemistry; Chemistry; Chemistry, Organic; Cyclization; Microwaves; Molecular Structure; Physical Sciences; Pyrroles - chemical synthesis; Pyrroles - chemistry; Science & Technology; SELECTIVE ELECTROPHILIC CYCLIZATION; ORGANIC-SYNTHESIS; PLAKINIDINE D; PALLADIUM-CATALYZED SYNTHESIS; ANTIMICROBIAL ACTIVITIES; ACRIDINE; 2,3-DISUBSTITUTED INDOLES; DERIVATIVES; MARINE SPONGE; ALKALOIDS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo400539x

An efficient cascade strategy for the direct synthesis of pyrrolo[3,2,1-de]acridones 4a–v, 5a–h from iodo-pyranoquinolines 2a–i by the palladium-catalyzed regioselective [3 + 2] alkyne annulation/ring-opening followed by intramolecular aldol condensation under microwave irradiation is described. The chemistry involves the in situ formation of pyrroloquinolines Y, via palladium-catalyzed selective [3 + 2] annulation of iodopyranoquinolines and internal akynes with ring-opening and successive intramolecular cross-aldol condensation. Both the symmetrical and unsymmetrical internal alkynes were reacted smoothly to provide the desired pyrroloacridones in good yields. This methodology provides the facile conversion of easily accessble iodopyranoquinoline into highly functionalized biologically important pyrroloacridones in a single process.