Directed ortho Metalation alkaloids

In a sequence that proceeds by tandem directed ortho metalation steps (Scheme 133) the N,N-diethyl isonicotinamide (447a) has been converted into the chemotherapeutic alkaloid ellipticine (589) (Scheme 182) (80JA1457). Thus, in a rapid, one-pot procedure, metalation of 447a followed by condensation with N-protected indole-3-carboxaldehyde derivatives leads to the intermediates 615 which, upon second metalation and aerial oxidation affords the quinones 616 in modest to good yields. Established steps were used to convert 616, R = CH2OMe into ellipticine (589), concluding a route which complements that based on the oxazolino DMG (Scheme 175). 

Directed ortho Metalation (DoM). The synthesis of the alkaloid schumarmiophytine requires a silicon protection of the more reactive ortho 0-carbamate site to set the stage for the key step, a remote anionic Fries rearrangement that results in a pyridine ring carbamoyl translocation (eq 48). ... 

Tandem Directed ortho Metalation-Metal - Halogen Exchange Route to Antitumor Ellipticine Alkaloids and Analogues... 

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