Natural
products and their analogues are significant sources of
therapeutic lead compounds. However, synthetic strategies for generating
large collections of these molecules remain a significant challenge.
The most difficult step in their synthesis is the design of a common
intermediate that can be easily transformed into natural products
belonging to different families. This study demonstrates the evolution
of synthetic tactics designed to assemble the functionalized piperidines
present in indole alkaloids from a common intermediate. More importantly,
we also report a previously unknown Ir- and Er-catalyzed dehydrogenative
spirocyclization reaction that enables direct access to spirocyclic
oxindole alkaloids. As a practical application, the asymmetric total
syntheses of 29 natural alkaloids belonging to different families
were accomplished by following a uniform synthetic route. The proposed
methodology extends the capability of the iridium-catalyzed dehydrogenative
coupling reaction to the realm of indole–alkaloid synthesis
and provides new opportunities for the efficient preparation of natural
product-like molecules.