Angewandte
Chemie
Figure 5. a) Space-filling representation of computed lowest energy co-
À
conformation of 6(PF6)2. b) Multiple C H···O hydrogen bonding
interactions indicated by the stick model. Hydrogen-bonding distances
À
C···O, H···O [ꢀ] and angles C H···O [8]: 1) 3.49, 2.61, 138.6; 2) 3.45,
2.87, 147.5; 3) 3.59, 2.59, 154.1; 4) 3.47, 2.64, 133.6.
imine bonds of the macrobicyclic component were nearly
coplanar with the phenylene cores to form the “ceiling” and
the “floor” that have extended p surfaces. The distance
between the centroids of the “ceiling” and the “floor” and
the mean plane of bpy unit is 3.6 ꢀ, which is indicative of p–p
interactions. The co-conformation was further stabilized by
Figure 3. Partial 1H NMR spectra (298 K, 500 MHz) of a) 1 and 2 (2:3)
in CDCl3, b) 5(PF6)2 alone in CDCl3/CD3CN (1:1), and c) 1, 2, and
5(PF6)2 (2:3:1) in CDCl3. The asterisk indicates residual CHCl3.
À
multiple C H···O hydrogen bonds between 1) Has of the bpy
comparison, the mixture of 1 and 2 in the absence of 5(PF6)2
resulted in a nonspecific mixture only (Figure 3a).
Two-dimensional nuclear Overhauser effect spectroscopy
(2D NOESY) 1H NMR spectra (Figure 4) provided unequiv-
ocal evidence for the interlocked structure of 6(PF6)2. For
example, the Ha protons of the bpy unit in the dumbbell
unit and the oxygen atoms on the two nearby ethylene glycol
loops on the back and 2) Hb of the bpy unit and the oxygen
atom on the front ethylene glycol loop. Similar interactions
were also present in the aforementioned cryptand–bpy
systems reported by Gibson, Huang, and their respective
co-workers.[15,16b–e] In accordance with our original design, the
modeling results confirmed the combination of p–p stacking
and hydrogen-bonding interactions as the origin of the
thermodynamic selectivity expressed in the exclusive forma-
tion of [2]rotaxane 6(PF6)2.
We have reported a highly efficient one-pot [2+3] clipping
method to obtain a macrobicycle and a related [2]rotaxane
through sixfold imine bond formation. A linear bpy-based
p template has been shown for the first time to effectively
induce the formation of the cage-like, C3-symmetrical crypt-
and, despite the symmetry mismatch between the host and the
guest. Based on this p-templating protocol, a novel [2]rotax-
ane 6(PF6)2 was assembled as the only product from a six-
component mixture. The high efficiency is reminiscent of
enzymatic catalysis,[23] in that the binding of 5(PF6)2 with an
intermediate, either acyclic or monocyclic, leads to a preor-
ganization of substrates into a conformation suitable for
macrobicyclization. The current method not only provides
facile access to cyclophane-based macrobicyclic hosts, but
also provides further opportunities for the assembly of
incrementally more complex interlocked systems with three-
dimensional structural features from simple starting materi-
als. Its application to the template-directed synthesis of
catenanes and suitanes[10d] is currently underway.[24]
Figure 4. Partial 2D NOESY spectrum (CDCl3, 298 K, 500 MHz) of
6(PF6)2.
component show strong NOEs with the imine protons Ha2 and
the aromatic protons Hb1 of the macrobicyclic component
while weakly correlating to Ha1 and Hb2 ; this correlation is
consistent with the relative spatial arrangements of the
aromatic units. In addition, the protons of ethylene glycol
side-loops show correlations to Ha and Hb of the bpy
(Figure 4) as well as to Hg on the dumbbell (see the
Supporting Information). The cross-peaks between the dumb-
bell and the macrobicyclic components are indicative of
threaded species, that is, 6(PF6)2 , as opposed to nonthreaded
complexes.
Experimental Section
Synthesis of [2]rotaxane 6(PF6)2. A mixture of 1 (5.3 mg, 32 mmol) and
2 (7.2 mg, 48 mmol) in CDCl3 (1 mL) was stirred at room temperature
for 1 hour. After the addition of 5(PF6)2 (26.0 mg, 16 mmol), the
mixture was stirred for a further 2 h. The resulting yellow solution was
filtered through a short plug of cotton wool, followed by evaporation
of the filtrate to give 6(PF6)2 as a pale yellow solid (36.0 mg, 97%).
1H NMR (CDCl3, 500 MHz, 298 K): d = 8.78 (d, J = 6.0 Hz, 4H), 8.10
(s, 4H), 7.89 (s, 2H), 7.77 (s, 2H), 7.22 (d, J = 8.5 Hz, 12H), 7.13 (s,
Multiple noncovalent interactions were identified from
the lowest energy co-conformation of 6(PF6)2 (Figure 5)
computed by force-field modeling.[22] As expected, the
Angew. Chem. Int. Ed. 2009, 48, 4185 –4189
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4187