Application of cascade processes toward heterocyclic synthesis
A. Padwa
Department of Chemistry, Emory University, Atlanta,
GA 30322, USA
Abstract: The reactions of N-acyliminium ions with tethered
p-bonds are among the most important methods
for preparing complex nitrogen-containing heterocycles. Pummerer-based
cyclizations are also finding widespread application in both carbo-
and heterocyclic syntheses. As part of a program concerned with new
methods for alkaloid synthesis, we became interested in using a linked
Pummerer/N-acyliminium ion cyclization sequence since we felt
that this combination offers unique opportunities for the assemblage
of complex target molecules. A synthetic method that combines transformations
of different reaction types significantly broadens the scope of such
procedures in synthetic chemistry. a-Thiocarbocations
generated from the Pummerer reaction of b-phenylsulfinylmethyl-a,b-unsaturated
amides can be intercepted by the adjacent amido group to produce transient
amino- substituted furans, which undergo subsequent Diels-Alder cycloadditions.
Using this domino amido-Pummerer/Diels-Alder cascade, we were
able to assemble novel polycyclic systems in a single operation. The
key step in the process involves the generation of a reactive N-acyliminium
ion by fragmentation of an amino-substituted [4+2] cycloadduct. The
successful synthesis of a number of alkaloids by this sequence of reactions
reveals the usefulness and importance of this unique domino cascade.
*Lecture presented at the 14th International Conference
on Organic Synthesis (ICOS-14), Christchurch, New Zealand, 14-18 July
2002. Other presentations are published in this issue,
pp. 1-70.
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