Inside and outside N-bridged cavity systems: Evidence for syn- and anti-atropisomers in scaffolds containing two N-benzoyl 7-azanorbornane units

Article abstract of DOI:10.1016/S0040-4039(00)01939-0

Alkene and aziridine reagents containing N-benzoyl 7-azanorbornane components have been prepared and used to construct [n]polynorbornanes in a block building protocol. The presence of syn- and anti-atropisomers involving the restricted rotation of the N-COPh bridge was established by ¹H NMR spectroscopy in an NNN-[3]polynorbornane 4 (outside bridges) whereas the anti-conformer dominated in a cavity NCOCOCN-[7]isopolynorbornane 8 (inside bridges, X-ray confirmation) prepared by a dual 1,3-dipolar addition of an acute-angled norbornene 6 with a hexacyclic bis-epoxide 7.

Full text of DOI:10.1016/S0040-4039(00)01939-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 465–468
Inside and outside N-bridged cavity systems: evidence for
syn- and anti-atropisomers in scaffolds containing two
N-benzoyl 7-azanorbornane units
Ronald N. Warrener* and Guangxing Sun
Centre for Molecular Architecture, Central Queensland University, Rockhampton, Queensland 4702, Australia
Received 13 October 2000; accepted 2 November 2000
Abstract—Alkene and aziridine reagents containing N-benzoyl 7-azanorbornane components have been prepared and used to
construct [n]polynorbornanes in a block building protocol. The presence of syn- and anti-atropisomers involving the restricted
rotation of the N-COPh bridge was established by 1H NMR spectroscopy in an NNN-[3]polynorbornane 4 (outside bridges)
whereas the anti-conformer dominated in a cavity NCOCOCN-[7]isopolynorbornane 8 (inside bridges, X-ray confirmation)
prepared by a dual 1,3-dipolar addition of an acute-angled norbornene 6 with a hexacyclic bis-epoxide 7. © 2001 Published by
Elsevier Science Ltd.
The development of block coupling protocols for the
preparation of [n]polynorbornane scaffolds has been
explored in some detail by our research group.1–4 Those
involving 1,3-dipolar reagents formed by the thermal
ring-opening of ester-activated cyclobutane epoxides2
and aziridines3 and their coupling with norbornene
dipolarophiles have been especially valuable, not least
because of the high stereoselectivity of the coupling
process. In this communication, we describe the synthe-
sis of novel [n]polynorbornanes containing N-benzoyl
7-azanorbornane subunits and report a special type of
atropisomerism in an NNN-[3]polynorbornane system
having two such subunits.
While the objective of the present study was to establish
a new route to cavity systems with inside N-bridge
functionality (see later), once again the [n]poly-
norbornane frame provided the medium by which an
Scheme 1.
Keywords: atropisomerism; 7-azanorbornanes; X-ray crystallography; restricted rotation; amides.
* Corresponding author. Tel.: 61 7 4930 9845; fax: 61 7 4930 9917; e-mail: r.warrener@cqu.edu.au
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01939-0

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R. N. Warrener, G. Sun / Tetrahedron Letters 42 (2001) 465–468
unusual aspect of bridge nitrogen chemistry could be
identified. We recently reported4 that N-benzyl XNY-
[3]polynorbornanes could be used to study nitrogen
hybridisation where it was shown that significant com-
pression towards planar nitrogen could be achieved by
through-space effects involving the proximal X and Y
bridges. Further, in cases where X=Y, dynamic inver-
tomerisation occurred and individual invertomers could
not be identified, even at low temperatures.
product with C2v-symmetry. Further support for the
involvement of restricted rotation of the N-benzoyl
group was forthcoming from the starting reagents 1 and
1
3 which each exhibited unsymmetrical, broadened H
NMR spectra at room temperature that became sym-
metrical at higher temperatures. To the best of our
knowledge, the detection of 4a and 4b is a new form of
atropisomerism in N-bridged alicyclic systems.9,10
Turning next to the formation of a cavity system with
inner-surface N-bridges, we approached this by the
retrosynthetic analysis shown in the box in Scheme 2.
This block approach used an alternative 1,3-dipolar
coupling technique (ACE coupling)2 and was applied
twice-over to bis-epoxide 7. The reaction depended on
the exo,exo-specific coupling protocol established for
norbornenes and employed the dipolarophilic norbor-
nene 6 that was produced in a stereoselective exo,endo-
fashion by addition of cyclopentadiene 5 to the
7-azabenzonorbornadiene 3.11 The asymmetry of the 1H
NMR spectrum of 6 reinforced the fact that restricted
rotation was again in effect and this was especially
evident in the wide shift separation of the olefinic
protons Hd, He (Dl=0.43) owing to their proximity to
the planar N-benzoyl group. This stereochemistry was
further reinforced by the lack of vicinal coupling be-
tween protons Hb and either Ha or Hc. Addition of 6
to 7 was achieved by heating (CHCl3, 140°C, sealed
tube, 12 h) and the cavity product 8 isolated by chro-
matography in 30% yield, following recrystallisation
Reaction of N-benzoyl 7-azabenzonorbornadiene 35
with the N-benzoyl bridged aziridine 16 formed the
NNN-[3]polynorbornane 4 (Scheme 1) in a 1,3-dipolar
reaction which involved the attack of 3 onto dipole 2.
1
The unusual feature of adduct 4 was evident in the H
NMR spectrum which was not only unsymmetrical
owing to the slow rotation of the amide bond7 but
exhibited a dual set of resonances (Fig. 1). The N-ben-
zyl group in 4 should be compressed by the flanking
N-benzoyl groups and was expected to exhibit rapid
invertomerisation at room temperature (see above) and
this ruled out N-benzyl invertomerisation being the
cause of the spectral duality. It was significant that the
proportion of products was not equal and that we were
dealing with two different species. We propose that an
equilibrium between two atropisomers was involved
owing to slow, restricted rotation of the N-COPh
bridges,8 which in 4 gave rise to a mixture of syn-at-
ropisomer 4a and anti-atropisomer 4b, products which
differed only in the relative orientation of the two
N-COPh conformers. This proposal was supported by
1H NMR spectroscopy where the complex spectrum at
room temperature was attributed to a mixture (ratio
0.6:1) of syn-atropisomer 4a and anti-atropisomer 4b
(assignments shown in Fig. 1). The minor syn-isomer 4a
had a mirror plane through the central N-bridge and
the two ester groups at the bridgehead were different
(singlets l 3.67, 4.05) whereas the N-benzylic methylene
protons were equivalent (singlet, l 4.30). The major
anti-isomer 4b had an axis of symmetry through the
central N-bridge and the ester groups at the bridgehead
were equivalent (singlet, l 3.85) while the N-benzylic
methylene protons were diastereotropic (doublet, l
4.08, 4.51 J=16.3 Hz). VT-NMR showed that the
spectrum broadened on heating yet retained asymmetry
to ca. 90°C and coalesced at around 110°C to yield a
broad but symmetrical spectrum consistent with a
1
from chloroform, mp >350°C. The H NMR spectrum
of 8 displayed spectral broadening of some signals,
however the presence of distinct atropisomers was not
apparent. An X-ray crystal structure of 8 (Fig. 2)12
confirmed the cavity structure and the attendant curva-
ture of the frame which brought the nitrogen bridges
,
within 9.4 A of each other. Further, it showed that the
N-benzoyl groups were essentially planar and had
adopted the anti-conformation in the solid state. The
anti-conformation of the N-benzoyl group may also
dominate in solution since molecular modelling indi-
cated that the phenyl groups in the syn-atropisomer are
capable of spatial overlap in some conformations. Such
proximity would make this conformer much higher in
energy than the well-separated anti-atropisomer,
thereby accounting for the lack of separate atropiso-
1
mers being observed in the H NMR spectrum for 8.
Figure 1. 1H NMR spectrum of atropisomers 4a and 4b (resonances starred).

R. N. Warrener, G. Sun / Tetrahedron Letters 42 (2001) 465–468
467
Scheme 2.
In conclusion, we have demonstrated the role of 1,3-dipo-
lar coupling techniques to produce N-benzoyl bridged
scaffolds and cavity systems, and shown for the first time
that compounds containing two such bridges are capable
of existing as atropisomeric pairs owing to the restricted
rotation of the amide NꢀCO bond. We are currently
seeking ways to stabilise atropisomers of this type so that
individual atropisomers are capable of isolation.
Acknowledgements
G.S. thanks Central Queensland University for the
provision of a CQU Ph.D. scholarship. We thank Dr. A.
Lough (University of Toronto) for conducting the X-ray
structure of 8.
Figure 2. X-Ray structure12 of cavity system 8.

468
R. N. Warrener, G. Sun / Tetrahedron Letters 42 (2001) 465–468
6. Aziridine 1 was formed from 3 by conversion to the
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