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Stereochemical Studies of Fluorescent Tröger’s Bases
David E. Lewis, Department of Chemistry, University of Wisconsin-Eau Claire, Eau Claire, WI 54702
The Tröger’s base skeleton is a rigid framework containing two chiral nitrogen atoms
at bridgehead positions. Under acid catalysis, the ring system undergoes inversion,
but two mechanisms for the inversion have been proposed Our primary goal is to
use symmetrically substituted chiral Tröger’s bases to probe the mechanism of this
ring inversion. The synthesis of the required chiral compounds will require the
synthesis of the optically pure 4-amino-3-(1-hydroxyethyl)-N-alkyl-1,8-naphthal-imides,
and then condensing them. The synthesis of the required alcohols continues to be
problematic.
O
NH2 OH
N
O
N
R
N
O
O
Attempts to incorporate a carbon substituent at C-3
Substitution of the halogen in the 3-bromo-4-alkylamino-1,8-naphthalimides, which
we have reported previously, has proved to be much less reproducible than we
had expected. We have found it difficult to reproduce the results from last year,
which makes this reaction extremely problematic for use in the synthesis of the
Tröger’s bases needed for the stereochemical study. In an attempt to utilize the
dealkylation of the 4-alkylamino group in the easily prepared 4-alkylamino-3bromo-N-alkyl-1,8-naphthalimides, we have examined the reactions of this system
with electrophiles and free radical oxidizing agents. In neither case was the
alkylamino group affected. We have begun pursuing a new strategy for the
preparation of the 3-acyl-4-amino-N-alkyl-1,8-naphthalimides by oxidation of a
suitable indole derivative.
This involves the synthesis of the benzo[de]pyrrolo[2,3-g]isoquinoline ring system by means of a Fischer indole synthesis.
We have succeeded in obtaining the required indole, but only in low yields and
impure state. We are working to optimize the reaction.
R
N
O
N
R
Cl
O
NHNH2
H2NN2

(63-79%)
O
N
O
n-Bu
O
N
O
n-Bu
O
r.t.
(>40%)
HN
HN
N
H3PO4

O
N
O
n-Bu
O
N
O
n-Bu