Abstract
Retrosynthetic deconstruction of a core aromatic ring is an especially simplifying
retrosynthetic step, reducing the complexity of the precursor synthetic target. Moreover,
when implemented to provide a penultimate intermediate, it enables late-stage divergent
aryl introductions, permitting deep-seated core aryl modifications ordinarily accessible
only by independent synthesis. Herein, we highlight the use of a ketone carbonyl group
as the functionality to direct such late-stage divergent aryl introductions onto a
penultimate intermediate with a projected application in the total synthesis of vinblastine
and its presently inaccessible analogues containing indole replacements. Although
the studies highlight this presently unconventional strategy with an especially challenging
target in mind, the increase in molecular complexity (intricacy) established by the
synthetic implementation of the powerful retrosynthetic disconnection, the use of
a ketone as the precursor enabling functionality, and with adoption of either conventional
or new wave (hetero)aromatic annulations combine to define a general and powerful
strategy suited for widespread implementation with near limitless scope in target
diversification.
Key words
alkaloids - annulations - arenes - cycloaddition - heterocycles - vinblastine - late-stage
modification - retrosynthetic disconnection - natural products
