Metal-Free Rapid Diastereoselective Construction of Isocryptolepine Core via Elecrophilic Dearomatization - Inramolecular Michael Addition Sequence

A method for rapid construction of indolo[3,2-l]acridin-7-one systems bearing isocryptolepine scaffold is described. Metal-free condensation of (4-methoxyphenyl)cyclohexan carbinols with ortho-amino/hydroxybenzonitriles in concentrated sulfuric acid yields polyannulated compounds with four new stereogenic centers in a highly diastereoselective manner. The reaction includes elecrophilic dearomatization of methoxyarene, formation of spirocyclic intermediate and intramolecular 1,4-nucleophilic addition sequence.

Automated summary

A method for rapidly constructing indolo[3,2-l]acridin-7-one systems bearing an isocryptolepine scaffold is described. The method involves a metal-free condensation reaction in concentrated sulfuric acid, resulting in the formation of polyannulated compounds with four new stereogenic centers in a highly diastereoselective manner. The reaction includes elecrophilic dearomatization of a methoxyarene, formation of a spirocyclic intermediate, and an intramolecular 1,4-nucleophilic addition sequence.