Studies Directed toward the Synthesis of Aspidophytine: Construction of Its Perhydroquinoline Core

We
have developed an efficient route for the synthesis of the perhydroquinoline
core of the indole alkaloid aspidophytine (2), starting
from commercially available and inexpensive 3-acetylpyridine. This
densely functionalized perhydroquinoline core displays four contiguous
stereocenters including an all-carbon quaternary center. The synthetic
sequence features a highly effective Diels–Alder reaction using
a carbamate-substituted siloxy diene accompanied by a spontaneous
intramolecular substitution of the newly formed 3°-alkyl bromide
with a carbamate group. The installation of the electron-rich aniline
moiety was accomplished via a TBSOTf-mediated intramolecular aza-Michael
reaction, and the relative stereochemistry of the aza-Michael product
(30) was confirmed by X-ray crystallographic analysis.
Among the useful transformations that were developed through this
study is a highly enantioselective Diels–Alder reaction of
a versatile cyclic carbamate siloxy diene.