Regioselection Switch in Nucleophilic Addition to Isoquinolinequinones: Mechanism and Origin of the Regioselectivity in the Total Synthesis of Ellipticine
2022
Castro, Joaquim A. M. | Serikava, Bruno K. | Maior, Christian R. S. | Naciuk, Fabrício F. | Rocco, Silvana A. | Ligiéro, Carolina B. P. | Morgon, Nelson H. | Miranda, Paulo C. M. L.
Ellipticine was synthesized in six steps and 20% global yield starting from the readily available 2,5-dimethoxy isoquinoline. Unprecedented regioselective control of the nucleophilic attack on the isoquinoline-5,8-dione is first described. Investigation of the possible pathways of this transformation through density functional theory calculations reveals unexpected N-oxide assistance in cascade tautomerizations, which was crucial for directing the nucleophilic attack and hastening the overall process. Using this strategy, we prepared the aniline-isoquinolinedione adduct and submitted it to an intramolecular double C–H cross-coupling activation to furnish ellipticinequinone, which gave ellipticine after a MeLi addition/BH₃ reduction sequence.
Show more [+] Less [-]Bibliographic information
This bibliographic record has been provided by National Agricultural Library