Positive cooperativity in the template-directed synthesis of monodisperse macromolecules

Article abstract of DOI:10.1021/ja2107564

Two series of oligorotaxanes R and R′ that contain -CH ₂NH₂⁺CH₂- recognition sites in their dumbbell components have been synthesized employing template-directed protocols. [24]Crown-8 rings self-assemble by a c

Full text of DOI:10.1021/ja2107564

Article
pubs.acs.org/JACS
Positive Cooperativity in the Template-Directed Synthesis of
Monodisperse Macromolecules
Matthew E. Belowich,† Cory Valente,† Ronald A. Smaldone,† Douglas C. Friedman,† Johannes Thiel,‡
Leroy Cronin,*,‡ and J. Fraser Stoddart*,†,§
†Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3133, United States
‡School of Chemistry, University of Glasgow, University Avenue, Glasgow G12 8QQ , United Kingdom
§NanoCentury KAIST Institute and Graduate School of EEWS (WCU), Korea Advanced Institute of Science and Technology
(KAIST), 373-1 Guseong Dong, Yuseong Gu, Daejeon 305-701, Republic of Korea
S
* Supporting Information
+
ABSTRACT: Two series of oligorotaxanes R and R′ that contain −CH2NH2 CH2− recognition
sites in their dumbbell components have been synthesized employing template-directed protocols.
[24]Crown-8 rings self-assemble by a clipping strategy around each and every recognition
site using equimolar amounts of 2,6-pyridinedicarboxaldehyde and tetraethyleneglycol bis-
+
(2-aminophenyl) ether to efficiently provide up to a [20]rotaxane. In the R series, the −NH2 −
recognition sites are separated by trismethylene bridges, whereas in the R′ series the spacers are
p-phenylene linkers. The underpinning idea here is that in the former series, the recognition
sites are strategically positioned 3.5 Å apart from one another so as to facilitate efficient [π···π]
stacking between the aromatic residues in contiguous rings in the rotaxanes and consequently, a
discrete rigid and rod-like conformation is realized; these noncovalent interactions are absent in
the latter series rendering them conformationally flexible/nondiscrete. Although in the R′ series,
the [3]-, [4]-, [8]-, and [12]rotaxanes were isolated after reaction times of <5−30 min in yields
of 72−85%, in the R series, the [3]-, [4]-, [5]-, [8]-, [12]-, [16]-, and [20]rotaxanes were
isolated in <5 min to 14 h in 88−98% yields. It follows that while in the R′ series the higher order oligorotaxanes are formed in
lower yields more rapidly, in the R series, the higher order oligorotaxanes are formed in higher yields more slowly. In the R
series, the high percentage yields are sustained throughout, despite the fact that up to 39 components are participating in the
template-directed self-assembly process. Simple arithmetic reveals that the conversion efficiency for each imine bond
formation peaks at 99.9% in the R series and 99.3% in the R′ series. This maintenance of reaction efficiency in the R series can
be ascribed to positive cooperativity, that is, when one ring is formed it aids and abets the formation of subsequent rings
presumably because of stabilizing extended [π···π] stacking interactions between the arene units. Experiments have been
performed wherein the dumbbell is starved of the macrocyclic components, and up to five times more of the fully saturated
rotaxane is formed than is predicted based on a purely statistical outcome, providing a clear indication that positive
cooperativity is operative. Moreover, it would appear that as the R series is traversed from the [3]- to the [4]- to the
[5]rotaxane, the cooperativity becomes increasingly positive. This kind of cooperative behavior is not observed for the
analogous oligorotaxanes in the R′ series. The conventional bevy of analytical techniques (e.g., HR-MS (ESI) and both 1H and
13C NMR spectroscopy) help establish the fact that all the oligorotaxanes are pure and monodisperse. Evidence of efficient
[π···π] stacking between contiguous arene units in the rings in the R series is revealed by 1H NMR spectroscopy. Ion-mobility
mass spectrometry performed on the R and R′ series yielded the collisional cross sections (CCSs), confirming the rigidity of
the R oligorotaxanes and the flexibility of the R′ ones. The extended [π···π] stacking interactions are found to be present in the
solid-state structures of the [3]- and [4]rotaxanes in the R series and also on the basis of molecular mechanics calculations
performed on the entire series of oligomers. The collective data presented herein supports our original design in that the
extended [π···π] stacking between contiguous arene units in the rings of the R series of oligorotaxanes facilitate an essentially
rigid rod-like conformation with evidence that positive cooperativity improves the efficiency of their formation. This situation
stands in sharp contrast to the conformationally flexible R′ series where the oligorotaxanes form with no cooperativity.
suffers from yields of less than 1%, to strategies using covalent
templates4 which generally improved the yields but require
many (commonly >20) synthetic steps. In 1983, Sauvage and
INTRODUCTION
■
Molecules which contain mechanical bonds1 have been targets
of interest to synthetic chemists ever since the first reported syn-
thesis of a catenane by Wasserman2 in 1960. Early approaches
to the syntheses of rotaxanes as well as catenanes evolved from
being all but statistical2,3 in the beginning, a strategy which
Received: December 7, 2011
Published: February 3, 2012
© 2012 American Chemical Society
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co-workers5,6 opened up the field of mechanically interlocked
molecules1 (MIMs) when they introduced metal-templating7 as
an efficient synthetic route to catenanes and rotaxanes. Their
seminal work represented a paradigm shift in the way MIMs
were prepared. This important advance led8 to the uncovering
of noncovalent templates based on solvophobic forces,9 donor−
acceptor interactions,10 hydrogen bonding, both neutral11 and
charged,12 electrostatic interactions involving anions,13 and, most
recently, radicals.14
results in the formation of a series of [n]rotaxanes (n = 2 − 11)
in less than 1 h at room temperature. Computational investiga-
tions33g lead one to believe that these oligorotaxanes assume
flexible conformations in solution, behaving as randomly assem-
bled coils. This conformation hampers drastically the potential
of these molecules to serve as energy transport mediators, for
example. We, therefore, have become very interested in control-
ling the overall conformation of such oligorotaxanes, i.e., making
them rigid and rod-like. We reasoned that [π···π] stacking inter-
actions between adjacent rings would not only provide added
stability to the oligorotaxanes, improving the efficiency of the
clipping reaction, but would also lend linearity and rigidity to
the molecules, rendering them rod-like. Specifically, we ratio-
Pedersen’s serendipitous discovery15 of the crown ethers16
and the fact that they form complexes with organic as well as
metal cations is widely regarded today as having marked a
defining moment which led to the subsequent development by
Lehn17 of a discipline which he was later to popularize under
the banner of supramolecular chemistry.18 As this field of
small molecule recognition and self-assembly started to unfold,
Cram19 launched a research program under the umbrella of
host−guest chemistry20 wherein he investigated21 the binding
+
nalized (Figure 1) that placing n-CH2NH2 CH2− recognition
+
between primary alkylammonium (RNH3 ) ions and crown
ethers in the constitutional range from [18]crown-6 up to
[20]crown-6 derivatives. The face-to-face complexes formed
+
between RNH3 ions and these crown ethers are stabilized
by strong [N+−H···O] hydrogen bonds in addition to dipole−
dipole interactions. Eventually in 1995, it was discovered inde-
pendently in our laboratories,22 as well as in those of Busch23
that, by increasing the size of the crown ether to a [24]crown-8
constitution, e.g., dibenzo[24]crown-8 (DB24C8), threading
Figure 1. Design of rigid rod-like polyrotaxanes based on [π···π]
stacking interactions between aromatic rings separated by 3.5 Å.
+
sites approximately 3.5 Å apart from one another in the dumb-
bell components of the oligorotaxanes would position the rings
so as to optimize their inter-ring [π···π] stacking interactions.
Although we have shown35 that this approach is effective in
preparing rod-like [n]rotaxanes (n = 2−8), the production of
well-defined, homogeneous, higher-order polyrotaxanes has
continued to be a challenge to us as synthetic chemists because
it (i) requires the synthesis of dumbbell templates with a well-
defined number of recognition sites and (ii) relies upon the
successful and efficient condensations of 2n components.
Herein, we report a detailed investigation (i) of the efficient
syntheses of two series of oligorotaxanes R and R′, (ii) on the
of secondary dialkyl-ammonium (R2NH2 ) ions through the
center of the larger macrocyclic polyether becomes a possibility.
This discovery led to the template-directed synthesis24 of
numerous rotaxanes and catenanes (i) by threading-followed-
by-stoppering25 and (ii) by slippage.26 Then, subsequently in
2001, we uncovered an extremely facile and efficient synthesis
of a [2]rotaxane using a clipping approach.27 The outcome,
when employing bis(3,5-dimethoxybenzyl)ammonium ions as
+
the source of templating −CH2NH2 CH2− centers, is a very
rapid and efficient formation of a macrocyclic diimine with a
[24]crown-8 constitution when 1.0 equiv each of 2,6-pyridine-
dicarboxaldehyde (44) and tetraethylene glycol bis(2-amino-
phenyl)ether (45) is added to a MeCN solution of the dumbbell
at room temperature. This thermodynamically driven self-assembly
process28 is stablilized by a number of noncovalent bonding
interactions including [N+−H···X] hydrogen bonds and
[N+−C−H···X] (X = O or N) interactions, as well as by
[π···π] stacking interactions between the dumbbell and ring
components of the [2]rotaxane. 2,5-Diformylfuran has also
been shown29 to be a suitable clipping partner, resulting in
enhanced templation, since the O atom in furan is a better
hydrogen bond acceptor than the N atom in pyridine, even
though the [2]rotaxane formation is considerably slower.
Polyrotaxanes, including main-chain-type,30 poly[n]-
rotaxanes,31 and cross-linked32, have been at the forefront33
of polymer and related materials-science research for more
than two decades now. The discovery28,29 of the highly efficient
clipping protocol made it feasible for us to prepare a series of
higher-order main-chain polyrotaxanes. Our strategy involves
the syntheses of a series of dumbbells which contain a discrete
+
profound effect that the distance between the −NH2 − recog-
nition sites has on the kinetics and thermodynamics of rotaxane
formation, and (iii) of the positive cooperativity that is present
in the formation of the R series of oligorotaxanes and absent in
the R′ series.
RESULTS AND DISCUSSION
■
In the beginning we focused our efforts on the synthesis of the
shorter oligoammonium dumbbells which involved (Scheme 1)
Scheme 1. Synthesis of the Dumbbells 2D·2PF6, 3D·3PF6,
and 4D·4PF6 by the Reductive Amination of 3,5-Dimeth-
oxybenzaldehyde (1) and Amino Compounds 5, 6, and 8,
Respectively
+
number of −CH2NH2 CH2− recognition sites spaced evenly
from one another along the rod section of the dumbbells.
Employing iterative reaction sequences, a series of dumbbells
+
consisting of n-C6H4−CH2NH2 CH2−C6H4− recognition sites
were prepared34 with 3,5-dimethoxyphenyl groups serving as stop-
pers. Addition of the dialdehyde 44 and diamine 45 (n equiv each)
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polar organic solvents such as acetone, acetonitrile, and nitro-
methane, and partially soluble in the less polar dichloromethane.
We also prepared a series of oligoammonium dumb-
bells which have a p-phenylene unit inserted between each of
Scheme 2. Synthesis of the Dumbbells 7D·7PF6, 11D·11PF6,
15D·15PF6, and 19D·19PF6, Employing Iterative Reaction
Sequences
+
the −CH2NH2 CH2− recognition sites. These templates would
ultimately give rise to a series of oligorotaxanes which serve as
control compounds against cooperative effects and conforma-
tion. The stepwise syntheses of the oligomeric dumbbells was
performed (Scheme 3) by the condensation of benzylamine
with benzaldehyde derivatives. In the synthesis of nD′·nPF6,
3,5-dimethoxybenzylamine (23) (2 equiv), and the diformyl-
terminated oligomers (24, 25, and 26) (1 equiv), which contain
a well-defined number of Boc-protected dialkylamine functions,
were condensed, affording the corresponding imines. The imine
functions were reduced to the corresponding dialkylamino groups
with NaBH4, and subsequent treatment with TFA resulted in
removal of all the Boc protecting groups, affording nD′·nPF6
after counterion exchange with an aqueous solution of saturated
NH4PF6.
The syntheses of the oligo-p-phenylene dumbbells utilizes
the diformylated component 37 and the primary amine 32 as
the key building blocks. The synthesis (Scheme 4) of 32 was
initiated with the reduction of methyl 4-cyanobenzoate (27).
[4-(Aminomethyl)phenyl]methanol hydrochloride (28) was
then reacted with 4-formylbenzonitrile (29) in the presence of
NaHCO3 to form the imine which was reduced with NaBH4 to
afford dialkylamine 30. The amino functionality was protected
with Boc2O and further reduction of the nitrile with LiAlH4
provided the building block 32. The diformyl building block
37 was synthesized employing a similar synthetic protocol,
beginning with reductive amination of methyl 4-formylbenzoate
(33) and 28, affording the dialkylamine 34 which was subseq-
uently Boc protected. Reduction of the methyl ester with
DIBAL and oxidation of each of the alcohols in 36 afforded 37.
Condensation (Scheme 5) of 37 with the primary amine 32
and subsequent reduction to the dialkylamine affords 38 in
85% yield. The amino functions were chemoselectively Boc-
protected, and the resulting diol 40 was subjected to Swern
oxidation, affording the diformyl-terminated oligomer 42, con-
sisting of five Boc-protected amino functions, and serving as
the precursor for the dumbbell component 7D′•7PF6. Alter-
natively, 42 can be subjected to a further iteration of the above
reaction sequence, beginning with reductive amination with
32, to afford the diformyl oligomer 43, consisting of nine
Boc-protected amino functions, which ultimately leads to the
preparation of 11D′·11PF6.
reductive amination between 3,5-dimethoxybenzaldehyde (1)
and the appropriate amine 5, 6, or 8. Protonation of every
secondary amino group along the dumbbell with HCl, followed
by counterion exchange, afforded the dumbbells 2D·2PF6,
3D·3PF6, and 4D·4PF6. (Throughout the remainder of this
manuscript, the dumbbell components will be designated as
+
nD·nPF6, where n is equal to the number of −CH2NH2 CH2−
recognition sites.) The primary challenge we faced in our goal
toward preparing a monodisperse [20]rotaxane was the develop-
ment of the synthetic methodology to prepare longer dumbbells
with up to 19 secondary dialkyl-ammonium recognition sites.
Along these lines, we employed a protocol (Scheme 2) where
by one end (stopper) of the dumbbell was extended in a stepwise
fashion. The first iteration started with the reductive amination
of 3,5-dimethoxybenzaldehyde (1) and diamine 9 to provide a
diamino-alcohol which was chemoselectively Boc protected,
affording the alcohol 10. Although several oxidants were screened
in the next step, i.e., PCC, IBX, Dess-Martin, and Ley oxidation,
they all led to poor conversion or decomposition of the starting
material. Swern oxidation, on the other hand, afforded the cor-
responding aldehyde 16 in good yield. In order to extend the
length of the dumbbell precursor, aldehyde 16 was subjected
to one, two, or three further iterations of the above reaction
sequence to afford the extended aldehydes 17, 18, and 20, res-
pectively. Each of the extended aldehydes was soluble in most
organic solvents and they were prepared on a multigram scale.
In the last step of the reaction sequence, the aldehydes 16, 17,
18, and 20 were subjected in turn to reductive amination, in a
one-pot reaction procedure, with bis(3-aminopropyl)amine
(21), followed by an acid-mediated global deprotection of
the amino groups with TFA and counterion exchange, affording
the polyammonium dumbbells 7D·7PF6, 11D·11PF6, 15D·
15PF6, and 19D·19PF6. Each of these polyammonium salts
were isolated in good yield, given the number of functional
group manipulations carried out in one pot, as pure compounds
without the need for chromatography. In contrast with some
other not dissimilar oligoammonium dumbbell components which
are poorly soluble,30 2D·2PF6−19D·19PF6 are highly soluble in
Scheme 3. Synthesis of the Oligomeric Dumbbells 3D′·3PF6,
7D′·7PF6, and 11D′·11PF6 from Dialdehydes 24, 25, and 26,
Respectively, and 3,5-Dimethoxybenzylamine (23)
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Scheme 4. Syntheses of the Building Blocks 32 and 37, Starting from 27 and 33, Respectively
With both series of oligoammonium dumbbells in hand, we
turned our attention toward the syntheses of the corresponding
oligorotaxanes. Beginning with the rigid series R, each of the
clipping reactions were performed in 0.75 mL of CD3CN and
monitored by 1H NMR spectroscopy. (The rotaxanes are
designated as nR·nPF6, where n is equal to the number of
−CH2NH2+CH2− recognition sites.) The [3]rotaxane 2R·2PF6 is
produced quantitatively (Figure 2a), on adding a solution con-
taining the dialdehyde 44 and diamine 45 (2 equiv each) to a
solution of the bisammonium salt 2D·2PF6 in CD3CN within
5 min of mixing the starting materials together. The chemical
shifts of the peaks associated with the imine (Hc), pyridyl
(Ha and Hb), and ortho-aryl (Hd−Hg) protons of a similar [2]-
rotaxane that was prepared27 previously are in good agreement,
and as expected, there is only a single set of resonances in
isolated (General Procedure I in the Experimental Section) in
93% yield as a yellow powder by layering iPr2O onto a solution
of 2R·2PF6 in CD3CN and collecting the precipitate by
filtration.
The [4]rotaxane was also prepared (Figure 3a) in almost
quantitative yield by addition of 3D·3PF6 to a solution of the
dialdehyde 44 and diamine 45 (3 equiv each) in CD3CN. The
1H NMR spectrum shows (Figure 3b) two sets of resonances in
a relative ratio of 2:1 as a result of the two homotopic outer
rings which are heterotopic with respect to the inner ring. Pure
3R·3PF6 was isolated in 90% yield and the ESI-MS of this
yellow powder confirmed the constitution of the [4]rotaxane
with intense base peaks being observed at m/z 2149.8608
([3R·2PF6]+), 1002.4507 ([3R·PF6]2+), and 619.9806 ([3R]3+).
The [5]rotaxane, 4R·4PF6, was prepared in a manner similar to
that of 3R·3PF6, and the spectroscopic evidence (see SI and
Table 1), 1H NMR spectroscopy and ESI-MS, is consistent with
the rotaxane having a rigid and linear conformation.
1
the H NMR spectrum for the two homotopic rings encircling
(Figure 2b) the dumbbell component. The constitution of the
[3]rotaxane was confirmed by the presence of an intense base
peak in the electrospray ionization (ESI) mass spectrum at m/z
1471.6220, corresponding to [2R·PF6]+. The [3]rotaxane was
Having established that the clipping protocol provides an
effective means of producing lower-order oligorotaxanes,
Scheme 5. Syntheses of the Bisformyl-Terminated Oligomers 42 and 43 Employing Iterative Reaction Sequences
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spectroscopy until equilibrium was reached (Table 1) in each
case. The spectrum of the [8]rotaxane, 7R·7PF6, consists of four
resonances in a 2:2:2:1 ratio in the region around δ = 8.00 ppm
for the imine protons of the rings. This observation can be
explained by the presence of three homotopic pairs of hetero-
topic rings (RA, RB, and RC), plus the central heterotopic ring
(RD). Furthermore, the chemical shifts of the imine protons
move upfield as they become more shielded toward the center
of the [8]rotaxane, i.e., the imine signal arising from RA appears
the furthest downfield (δ = 8.19 ppm), while the imine reso-
nance corresponding to RD, appears the furthest upfield (δ =
7.97 ppm). The incredible efficiency of the clipping protocol in
this case is reflected by the 94% isolated yield which correlates
with a 99.6% conversion efficiency for each imine bond formed
in the reaction. The ESI-MS of 7R·7PF6 confirms the structural
identity of the [8]rotaxane.
Formation of the [12]-, [16]-, and [20]rotaxanes required
10, 12, and 14 h at room temperature, respectively, for
the reactions to reach thermodynamic equilibrium. As the
lengths of the oligorotaxanes become longer and longer, they
begin to resemble polymers, a structural feature which is reflected
Figure 2. (a) Template-directed synthesis of the [3]rotaxane, 2R·2PF6
starting from 2D·2PF6, 44, and 45. (b) The 1H NMR spectrum
(500 MHz, CD3CN, 298 K) of the [3]rotaxane. The assignments of
the resonances are portrayed by partitioning the structural formula of
2R2+ into its separate dumbbell and ring components.
1
(Figure 4) by the broadened peaks in the H NMR spectra,
although, it should be noted that they are in fact discrete,
monodisperse products. Their formation can still be confirmed
by examining the chemical shifts and relative intensities of the
imine resonances. The spectrum of 11R·11PF6, for example,
displays four distinct imine resonances which integrate in a
4:4:4:10 ratio. The three homotopic pairs of heterotopic rings
nearest the stoppers (RA, RB, and RC) are shielded the least and
as a result the corresponding imine protons resonate at lower
field (δ = 8.18, 8.02, and 7.97 ppm, respectively). The more
namely 2R2+, 3R3+, and 4R4+, we turned our attention toward
the syntheses (Scheme 6) of higher-order oligorotaxanes with
up to 19 rings. Again, in all cases, clipping reactions were per-
formed in 0.75 mL of CD3CN by mixing together the dumbbell
(template) with a dynamic combinatorial library consisting of
+
n equiv (n = number of −CH2NH2 CH2− recognition sites) of
both the diamine 44 and the dialdehyde 45. The resulting
1
golden-yellow solutions were then monitored by H NMR
Figure 3. (a) Template-directed synthesis of the [4]rotaxane, 3R·3PF6 starting from 3D·3PF6, 44, and 45. (b) The 1H NMR spectrum (500 MHz,
CD3CN, 298 K) of the [4]rotaxane. The assignments of the resonances are portrayed by partitioning the structural formula of 3R3+ into its
separate dumbbell and ring components.
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Table 1. Numbers of Rings, Components, and Imine Bonds Formed in the Case of nR·nPF6, Alongside Characteristic Peaks
a
Observed in Their Respective Mass Spectra
compound
no.
[n]
no. of
no. of imine
bonds
time to reach
c
isolated yield yield per imine
molecular weight observed ESI-MS signals
f
b
d
e
rotaxane rings components
equilibrium
(%)
bond (%)
(g/mol)
(m/z)
2R2+
3R3+
3
4
2
3
5
7
4
6
<5 min
<5 min
93
90
98.2
98.3
1617
2296
1471.6220 [M − PF6]+
2149.8608 [M − PF6]+
1002.4507 [M − 2PF6]2+
619.9806 [M − 3PF6]3+
1341.5625 [M − 2PF6]2+
846.0558 [M − 3PF6]3+
1524.2985 [M − 3PF6]3+
1106.9836 [M − 4PF6]4+
856.5903 [M − 5PF6]5+
1786.2763 [M − 4PF6]4+
1400.0153 [M − 5PF6]5+
1142.5061 [M − 6PF6]6+
958.5858 [M − 7PF6]7+
1942.8957 [M − 5PF6]5+
1595.9068 [M − 6PF6]6+
1346.3478 [M − 7PF6]7+
1014.9535 [M − 9PF6]9+
898.9877 [M − 10PF6]10+
1734.1194 [M − 7PF6]7+
1499.1830 [M − 8PF6]B+
1316.6811 [M − 9PF6]9+
1170.5047 [M − 10PF6]10+
1050.6512 [M − 11PF6]11+
4R4+
7R7+
5
8
4
7
9
8
<5 min
6 h
88
94
98.4
99.6
2975
5011
15
14
11R11+
12
16
11
15
23
31
22
30
10 h
12 h
98
93
99.9
99.8
7725
15R15+
10439
19R19+
20
19
39
38
14 h
90
99.7
13154
a
b
The isolated yield and yield per lmine bond formed indicate the high efficiency and precision of the clipping reaction. The number of components
c
is determined for nR·nPF6 by 2n + l where n = number of equivalents of 44 or 45. Equilibrium times were determined by monitoring the clipping
d
1
reaction by H NMR spectroscopy until no changes in the spectra were observed. All clipping reactions were performed at room temperature
e
according to General Procedure I in the Experimental Section. The percent yield for each imine bond formed can be calculated by (Y)1/x where Y =
f
percent yield of nR·nPF6/100 and x = number of imine bonds formed. High-resolution electrospray ionization mass spectra were collected on
purified samples of nR·nPF6 redissolved in MeCN.
Scheme 6. Clipping Approach to the Template-Directed Syntheses of the Dynamic Oligorotaxanes nR·nPF6 from the
a
Oligoammonium Templates nD·nPF6 with n equiv Each of 44 and 45
a
The oligorotaxanes are structurally rigid on account of extended [π···π] stacking interactions between contiguous rings which are separated by
3.5 Å. These interactions also asist in the formation of contiguous rings along the backbone of the rotaxane resulting in extremely high conversion
efficiencies, up to 99.9%, for each imine bond.
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Figure 4. Partial 1H NMR spectra (500 MHz, CD3CN, 298 K) of the series of oligorotaxanes showing how the resonances for the imine (H−CN)
and aromatic protons (Ha/Hb and Hh/Hi) move to higher fields and, in the case of the benzo ring protons (Hd/He/Hf/Hg), fan out as more rings are
added on going from the [2]rotaxane up to the [20]rotaxane. These chemical shift changes are indicative of multiple [π···π] stacking interactions.
central of the rings (RD − RF), which experience the most
amount of shielding, share very similar chemical environments
and resonate at roughly the same frequencies (δ = 7.95 ppm). It
is important to note the amazing efficiencies of the multiple
clipping reactions involving 23 components, in the case of the
[12]rotaxane, whereby each and every recognition unit along
the dumbbell templates the formation of a ring. Moreover,
we do not detect any traces of the dumbbell that is not fully
saturated with rings, that is, consisting of 10 or fewer rings.
Furthermore, an isolated yield of 98% for 11R·11PF6 corres-
ponds to a 99.9% conversion efficiency per imine condensation!
dynamic acylic diene metathesis (ADMet) polymerization. Al-
though this protocol provides a facile procedure for the prepa-
ration of polyrotaxanes, it suffers from producing polymers with
relatively high polydispersity indeces (PDIs) with a maximum
of only 82% threading of the rings onto the recognition sites.
The second series of oligorotaxanes which have been de-
signed to prevent [π···π] stacking interactions between adjacent
rings by inserting a p-phenylene spacer between each of the
+
−CH2NH2 CH2− recognition sites, was prepared (Scheme 7)
in an analogous fashion. Clipping reactions were conducted in
CD3CN by mixing together the dumbbell templates nD′·nPF6
with n equiv each of compounds 44 and 45 and monitoring
(Table 2) the reaction mixtures by 1H NMR spectroscopy. The
spectrum (Figure 5) of the [3]rotaxane, 2R′·2PF6, which looks
very similar to that of 2R·2PF6, shows a single set of resonances
for the two homotopic rings. However, unlike the spectra of the
rotaxanes in the R series which were discussed previously, the
spectra of the [4]-, [8]-, and [12]rotaxanes, 3R′·3PF6, 7R′·7PF6,
and 11R′·11PF6, consist of only two sets of resonances for the
imine protons of the rings, the ratios between the two sets of
signals calculated by integration of the spectra being 2:1, 1:2.5,
and 1:4.5, respectively. This observation can be explained in
terms of the heterotopic environments of the rings surrounding
the dumbbells whereby the two homotopic rings adjacent to
the stoppers (RA) in the [4]rotaxane are heterotopic with
respect to the central ring (RB). In the [8]rotaxane, however,
rings RB and RC share very similar chemical environments (δ =
8.09 ppm) but differ from that of RA (δ = 8.26 ppm). The same
is true of RB, RC, and RD (δ = 8.08 ppm) in the [12]rotaxane.
The slight difference between rings RB and RC is even expressed
in the separation of the peaks for the imine protons (H′−CN).
The crucial difference between this set of spectroscopic data
1
The same behavior is observed in the H NMR spectra of
the [16]rotaxane 15R·15PF6, and also the [20]rotaxane 19R·
19PF6, wherein the three homotopic pairs of heterotopic rings
nearest the stoppers (RA, RB, and RC) are well resolved with
the ratios as determined by integration, for 15R·15PF6, being
4:4:4:18 where the resonances for the central rings overlap
extensively. The difference between the outermost rings of
these two oligorotaxanes is expressed by the imine protons. In
the clipping reactions with (n − 1) equiv each of 44 and 45, full
conversions to the saturated [n]rotaxane is observed. As was
the case with the shorter oligorotaxanes, we have looked for the
presence of the dumbbell templates that are not fully saturated,
i.e., 19R19+ with fewer than 19 rings, but do not observe any
traces of them by ESI-MS or diffusion-ordered spectroscopy
(DOSY). The isolated yields of 15R·15PF6 and 19R·19PF6 are
93 and 90% which translates to 99.8 and 99.7% conversion per
imine bond formed, respectively, during the clipping reactions.
By way of a comparison, Grubbs and co-workers36 have described
very recently an efficient one-pot synthesis of polyrotaxanes,
employing a supramolecular monomer consisting of a polymeri-
zable ammonium salt and crown ether in combination with
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Scheme 7. Clipping Approach to the Template-Directed Syntheses of the Dynamic Oligorotaxanes nR′·nPF6 from the
Oligoammonium Templates nD′·nPF6 with n equiv Each of 44 and 45
and the spectra for the R series is that the resonances
of the aromatic protons belonging to 2R′2+, 3R′3+, 7R′7+,
and 11R′11+ do not shift as a function of the number of rings
encircling the dumbbells. In fact, with the exception of the rings
(RA) closest to the stoppers, each remaining ring finds itself in
very similar chemical environments, as reflected by the fact that
and 10 h, respectively, to reach thermodynamic equilibrium
with conversions in excess of 99.8%. The interplay between
kinetics and thermodynamics in the formation of rotaxanes in
the R and R′ series is all too familiar: the more stable the prod-
ucts, the longer it takes for them to be formed. The conversion
efficiency for each imine bond formation in the clipping reac-
tions to afford the R′ rotaxanes range from 94.7 to 99.3%, while
the lowest conversion per imine bond formed in the R rotax-
anes is 98.2% and reaches up as far as 99.9% for 11R·11PF6.
The increased efficiency of production within the R series
compared with the R′ series could be the result of an additional
templation effect, wherein formation of one ring can template
the formation of a contiguous ring by, presumably, stabilizing
extended [π···π] stacking interactions. Although this difference
may not seem to be significant, it is actually highly relevant
when it comes to producing good yields of high molecular weight
compounds. The clipping reactions that are taking place along
the dumbbells may be likened to a step-growth polymerization
1
only two sets of resonances appear in the H NMR spectra.
This observation is a clear indication that adjacent rings are
not close enough to participate in [π···π] stacking interactions,
which suggests that the [n]rotaxanes are much more flexible
than 2R2+−19R19+
.
It is worthy to note that the different constitutions of the
dumbbells in the D and D′ series have a pronounced effect
on the kinetics and thermodynamics of the clipping reactions.
For example, under very similar reaction conditions, the [8]-
and [12]rotaxanes 7R′·7PF6 and 11R′·11PF6 form in >98%
conversion efficiencies in approximately 20−30 min whereas
the [8]- and [12]rotaxanes 7R·7PF6 and 11R·11PF6 require 6
Table 2. Numbers of Rings, Components, and Imine Bonds Formed in the Case of nR′·nPF6, Alongside Characteristic Peaks
Observed in Their Respective Mass Spectra
compound
no.
[n]
no. of
no. of
no. of imine time to reach
isolated
yield (%)
yield per imine molecular weight
observed ESI-MS
a
b
c
d
e
rotaxane rings components
bonds
equilibrium
bond (%)
(g/mol)
signals (m/z)
2R′2+
3R′3+
7R′7+
3
4
8
2
3
7
5
7
4
<5 min
86
72
78
96.3
1680
1533.6300 [M − PF6]+
1387.6610 [M − HPF6− PF6]+
694.3370 [M − 2PF6]2+
2127.9460 [M − HPF6−PF6]+
1064.4621 [M − 2PF6]2+
661.3218 [M − 3PF6]3+
1648.3245 [M − 3PF6]3+
1200.1020 [M − 4PF6]4+
931.0238 [M − 5PF6]5+
751.6797 [M − 6PF6]6+
2428.6179 [M − 3PF6]3+
1785.3202 [M − 4PF6]4+
6
8
<5 min
20 min
94.7
98.2
2420
5383
15
11R′11+
12
11
23
14
30 min
85
99.3
8346
a
b
The number of components is determined for nR′·PF6 by 2n+1 where n = number of equivalents of 44 or 45. Equilibrium times were determined
c
by monitoring the clipping reaction by 1H NMR spectroscopy until no changes in the spectra were observed. All clipping reactions were performed
d
at room temperature according to General Procedure I in the Experimental Section. The percent yield for each imine bond formed can be
e
calculated by (Y)1/x where Y = percent yield of nR′·nPF6/100 and x = number of imine bonds formed. High-resolution electrospray ionization mass
spectra were collected on purified samples of nR′·nPF6 redissolved in MeCN.
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major product. Integration of those resonances known to arise
from the imines of 3R3+ indicated that the [4]rotaxane accounts
for 75% of the species present in solution, while the remaining 25%
of the mass balance belongs to a combination of 3D3+, 1R3+ and
2R3+. All four of these species were identified as their PF6− salts in
the ESI-MS. A purely statistical mixture wherein no one species is
favored thermodynamically would result in the formation of only
17% of the [4]rotaxane. The fact that 3R3+ exists in quantities that
are more than four times that expected on a statistical basis, is a
clear indication that positive cooperativity is at play.
The analogous equilibrium experiment was performed
(Figure S10a) in the case of the [5]rotaxane 4R·4PF6 by add-
ing 2 equiv each of 44 and 45 to 4D·4PF6. Quantitative analysis
1
of the H NMR spectrum (Figure S10b) indicates that 4R4+ is
present in the reaction mixture at 50% while the remaining 50%
consists of 4D4+, 1R4+, 2R4+ ,and 3R4+. A purely statistical
mixture would have afforded only 10% of 4R4+ and so the
experiment results in five times more of the [5]rotaxane being
formed than would be expected on a statistical basis. Addi-
tionally, the positive cooperativity appears to be on the rise the
more recognition sites there are present on the dumbbell. This
increase in positive cooperativity as the R series of oligoro-
taxanes is mounted is consistent with the fact that the conver-
sion per imine bond in each case of the clipping reactions rises
(Table 1) from 98.2% in the case of the [3]rotaxane to 99.6%
in the [8]rotaxane and then remains more or less constant for
the [12]-, [16]-, and [20]rotaxanes in the range of 99.7−99.9%,
within experimental error.
1
Figure 5. Partial H NMR spectra (500 MHz, CD3CN, 298 K) of
2R′·2PF6, 3R′·3PF6, 7R′·7PF6, and 11R′·11PF6 showing how the
resonances for the imine (H−CN) and aromatic protons (Ha/Hb
and Hd/He/Hf/Hg) do not move to higher field upon the progressive
addition of more and more rings. This behavior is a result of the
absence of [π···π] stacking interactions between adjacent rings.
process for which it is well understood that very long linear
polymers are generally not attainable since even at 98%
conversion per reaction, the degree of polymerization37 (DP)
is still only 50. An increase of just 1% (i.e., 99% per reaction),
however, gives a DP of 100, while 99.9% conversion per reaction
correlates with a DP of 1000. Consequently, the methodology
we have developed could potentially be employed for the
syntheses of even higher order [n]rotaxanes (n ≥ 50) as a result
of the extended [π···π] stacking interactions increasing the
efficiency of each clipping reaction.
In order to find out if there is a cooperative effect at work
during the self-assembly of the oligorotaxanes in the R series,
we performed an experiment (Figure 6a) in which 2D·2PF6 was
added to a solution of only 1 equiv each of 44 and 45. There
are three potential outcomes from this experiment, (i) the
assembly of the second ring around 2D·2PF6 is more favorable
than the clipping of the first ring, i.e., there is positive coopera-
tivity38 resulting in the production of 2D2+ and 2R2+, (ii) the
formation of the second ring is not promoted i.e., there is zero
cooperativity, by the presence of the first ring and a statistical
mixture arises affording a 1:2:1 ratio of 2D2+: 1R2+: 2R2+, and
(iii) the formation of the second ring is prevented, i.e., there is
negative cooperativity, by the presence of the first ring and so
much more of 1R2+ than represented by a statistical mixture is
the outcome. In the event, once the dynamic system came to
equilibrium, the 1H NMR spectrum (Figure 6b) revealed that a
statistical mixture, scenario (ii), was the result and so it follows
that there is no cooperativity operating in this case.
Some insights into the conformations adopted by the R
series of oligorotoxanes can be obtained from a comparison of
the 1H NMR spectra (Figure 4) for 1R+−19R19+. In proceeding
from 1R+ to 2R2+, 3R3+, 4R4+, 7R7+, 11R11+, and 15R15+ all
of the way up to 19R19+, the resonances for the protons on
the rings that are nearest the stoppers of the dumbbells move
progressively upfield. The signal for the imine protons on the
outermost rings of the [20]rotaxane resonante 0.25 ppm up-
field relative to that in the [2]rotaxane. This upfield trend in
chemical shifts is also observed for the pyridyl (Ha and Hb) and
1
aryl (Hd−Hi) protons in the oligorotaxanes. These H NMR
spectral characteristics can be explained39 by the cumulative
number of [π···π] stacking interactions as the R series of
We decided that, although cooperativity is zero in the case of
2D2+, it might start to become positive when there are more
than two recognition sites on the dumbbell. We therefore chose
to carry out an equilibration involving the formation of the [4]-
and [5]rotaxanes. First of all, 3D·3PF6 was added (Figure S9a)
to a solution of 44 and 45 (1.5 equiv of each). At equilibrium,
Figure 6. (a) Reaction between 2D·2PF6 and 1.0 equiv each of 44 and
45 to probe a potential cooperative effect during the self-assembly
process. (b) The partial 1H NMR spectrum (500 MHz, CD3CN,
298 K) at equilibrium. The 1:2:1 ratio between 2D2+:1R2+:2R2+ is
indicative of a statistical distribution whereby no one species is favored
thermodynamically.
1
the H NMR spectrum (Figure S9b) showed 3R3+ to be the
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Table 3. Collisional Cross Sections (CCSs) and Drift Times
(tD) Associated with Different Charged States of the [3]-,
[4]-, [8]-, and [12]Rotaxanes
compound
m/z
charge
ccs (Å2)
tD (ms)
2R2+
1471.63
663.33
1533.65
694.33
1002.95
620.31
1064.97
661.68
2359.92
1524.96
1107.48
857.00
690.04
570.72
2545.96
1649.32
1200.76
932.62
752.19
623.87
1786.27
1400.02
1142.53
958.01
820.66
713.37
627.53
557.30
1941.30
1524.05
1245.87
1047.18
898.17
782.26
689.54
613.67
1
304.31
286.65
332.42
297.20
375.43
382.28
392.45
388.57
683.96
641.67
621.11
612.70
625.54
645.18
708.64
661.10
647.49
727.82
752.97
752.28
919.07
897.57
883.45
888.04
889.29
893.71
892.55
926.76
880.56
869.56
1044.33
1112.57
1114.63
1121.11
1111.50
1147.71
15.94
5.07
18.24
5.36
7.68
4.26
8.22
4.37
19.22
9.42
5.79
4.04
3.16
2.62
20.29
9.86
6.17
5.25
4.19
3.31
10.52
7.23
5.35
4.26
3.49
2.94
2.50
2.29
9.86
6.89
6.90
6.01
4.92
4.15
3.49
3.17
2
2R′2+
3R3+
3R′3+
7R7+
1
2
2
3
2
3
2
3
4
5
6
Figure 7. Collisional cross sections (CCSs) for the [8]rotaxanes 7R7+
and 7R′7+ plotted against the charge state of the ions.
7
7R′7+
2
7R′·nPF6, while the loss of six PF6− counterions results in only a
small increase in the CCS for 7R6+. The same behavior is
observed (Figure 8) in the case of the [12]rotaxanes, wherein
3
4
5
−
the removal of six PF6 counterions results in a dramatic
6
increase in the CCS of 11R′5+ while the CCSs of 11R·nPF6
remain relatively constant throughout the charge state series.
The initial decrease in CCSs for both series of the [8]- and
7
11R11+
4
5
−
[12]rotaxanes can once again be explained by the loss of PF6
6
counterions which contribute to the overall size of the ions. We
hypothesize that the counterions play a crucial role in balancing
the charge of the oligorotaxanes such that at the beginning of
the charge state series, both the R and R′ series are roughly the
same apparent size. However, as PF6− counterions are stripped
from the oligorotaxanes, the molecules distort so as to distance
the charges along the backbone of the dumbbells as far away
from one another as possible. In the case of the R′ series of
oligorotaxanes, this distortion is manifested in the increase in
CCSs. The greater flexibility of the R′ oligorotaxanes results in
more collisions with the gas molecules in the drift tube and
therefore a larger CCS value. On the other hand, the R series of
oligorotaxanes do not have the same freedom to “wiggle”
around as a result of the extended [π···π] stacking interactions
along their backbones. Consequently, fewer collisions occur
7
8
9
10
11
4
11R′11+
5
6
7
8
9
10
11
[n]rotaxanes is scaled from n = 2 to 20. This realization suggests
very strongly to us that the conformations of these oligorota-
xanes are rod-like in shape in solution.
For further analysis of the solution state behavior of the
oligorotaxanes, ion-mobility mass-spectrometry (IM-MS)40
was performed on the [3]-, [4]-, [8]-, and [12]rotaxanes.41
All compounds were dissolved in MeCN and injected into the
instrument using a syringe pump. For all four pairs, namely,
2R2+ and 2R′2+, 3R3+ and 3R′3+, 7R7+ and 7R′7+, and 11R11+ and
11R′11+, the R′ series of oligorotaxanes revealed (Table 3)
higher collision cross sections (CCSs) than the oligorotaxanes
in the R series. In the cases of the [3]- and [4]rotaxanes, the
CCSs decrease with increasing charge on account of the loss of
PF6− counterions which contribute to the overall size of the mole-
cules. The CCSs are larger for 2R′2+ and 3R′3+ than for 2R2+ and
3R3+, respectively, as a result of the bulkier xylylene linkers in the
dumbbells in the R′ series as compared to the propylene linkers in
the R series. For the [8]- and [12]rotaxanes, the CCSs initially
show the same behavior until they reach a threshold (Figure 7):
the removal of five PF6− counterions causes a dramatic increase
in the CCS of 7R′5+ as compared to the lower charged ions of
Figure 8. Collisional cross sections (CCSs) for the [12]rotaxanes
11R11+ and 11R′11+ plotted against the charge state of the ions.
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further using a 1 ns MD simulation at 300 K. The minimized
structures are portrayed in Figure 10.
Molecular mechanics show that the R′ series of oligorotax-
+
anes with p-phenylene spacers between the −CH2NH2 CH2−
recognition sites tend to adopt quite flexible conformations. Put
another way, the rings associated with the monomeric units
appear to take up random orientations with respect to each
other along the chains, resulting in conformations (Figure 10b)
with bends and kinks all of the way along their backbones. This
tendency to form flexible conformations was noted31 previously
when carrying out MD simulations on very similar oligorotax-
anes.
In the case of the R series of oligorotaxanes with propylene
+
+
spacers between the −NH2 − centers in the −CH2NH2 CH2−
recognition sites, their structures appeared to maintain linear
rod-like geometries overall throughout the course of the sim-
ulations. The molecules adopt conformations (Figure 10a) with
a much higher degree of internal order being expressed between
the rings of the repeating monomeric units. It also appears that the
extended [π···π] stacking interactions are conserved along the
entire backbone of the oligorotaxanes. This observation is in
good agreement with the crystal structures which have already
been discussed for 2R2+ and 3R3+ in the solid-state.
One notable feature revealed by the molecular mechanics on
the higher-order rotaxanes is their propensity to become curved
in shape as the DP of the oligorotaxanes increases. This phenom-
enon can be explained by the attraction of the arene residues,
one to the other through a combination of multiple hydro-
phobic and [π···π] stacking interactions counter balanced by
the electrostatic repulsions that must occur between the lone
pairs of electrons on the ether oxygen atoms of adjacent poly-
ether loops located on the opposite side of the rod-shaped
molecules from the arene residues. Moreover, based on the MD
simulations, we are inclined to speculate that polymeric ana-
logues of these oligorotaxanes could potentially form helical
arrays on a macroscopic (∼1 μm) scale.
Figure 9. (a) Stick and (b) space-filling representations of the solid-
state structure of 2R2+. The [N+−H···N] distances range from 2.93 to
3.04 Å between nitrogen atoms and have [N+−H···N] angles of 172
and 174°. (c) Stick and (d) space-filling representations of the solid-
state structure of 3R3+. Hydrogen atoms and counterions have been
omitted and discounted for clarity.
with the gas molecules in the drift tube and we do not observe a
significant increase in their CCS values.
Further information on the conformational behavior of the
oligorotaxanes can be gleaned from the solid-state structures of
the lower order rotaxanes, namely 2R2+ and 3R3+. Good quality
single crystals suitable for X-ray diffraction analysis were grown
by liquid−liquid diffusion of iPr2O into a solution of 2R·2PF6
in CH2Cl2. The solid-state structure (Figure 9a,b) of 2R2+
reveals42,43 that the three arenes in each of the two rings are in
register with one another and their average mean planes in all
cases are separated by the optimal [π···π] stacking distance of
3.5 Å. Importantly, the conformation of 2R2+ is stabilized by
four strong [N+−H···N] hydrogen bonds ranging between 2.93
and 3.03 Å between nitrogen atoms, plus additional [π···π]
stacking interactions between one of the terminal 3,5-dimethoxy-
phenyl stoppers on the dumbbell with one of the pyridyl units in
one of the rings, all acting in unison to impose a linear rigid
conformation on the [3]rotaxane 2R2+.
X-ray quality single crystals of 3R·3PF6 were also grown
by the vapor diffusion of tert-butylmethyl ether into a solution
of 3R·3PF6 in MeOH. In this case, the solid-state structure
(Figure 9 c/d) of 3R3+ reveals42,44 that the arenes in two of the
rings (RA and RB) are in register with one another, the average
mean planes between their stacked arenes are separated by a
distance of 3.5 Å, while the third ring (RC) is out of register
with the other two rings (RA and RB) by about 52°. The overall
message, nonetheless, of rigid rod-like conformations for the
molecules remains a forceful one.
All in all, the interplay between the hydrogen bonding and
[π···π] stacking interactions working in unison have proven
to effectively promote the self-assembly of oligorotaxanes in a
remarkably efficient way. Previously, a monodisperse poly-
ethylene glycol dumbbell (28-mer) was prepared30c and sub-
sequently threaded with α-cyclodextrins (α-CDs) and stop-
pered affording polyrotaxanes. In this case, a maximum of
In an attempt to shed some additional light on the confor-
mations adopted by these oligorotaxanes which could not be
obtained crystalline, a comprehensive molecular mechanics
investigation was initiated employing an approach that is an
adaption of previous molecular mechanics studies45 on rotax-
anes. Initial geometries were generated using coordinates from
the crystal structure of 2R·2PF6 as a template and the structures
were then minimized using a simulated annealing procedure.
Each structure was subjected to a sequence of 100 ps molecular
dynamics (MD) simulations using the OPLS2005 force field
with an implicit H2O solvation model starting at 450 K and
lowering the temperature in 25 degree increments until 300 K
was reached.46 The resulting structures were then minimized
Figure 10. Structures of oligorotaxanes minimized using a simulated
annealing procedure. The R′ series of oligorotaxanes containing a
p-phenylene spacer (a) have a considerably less ordered backbone
structure than those containing propylene spacer units in the R series of
oligorotaxanes (b). The MD simulations indicate that the stacking
interactions of nRn+ are conserved, even in lengths up to the [20]rotaxane.
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only 12 α-CDs were able to be threaded onto the dumbbell.
We later showed that a monodisperse [14]rotaxane could be
prepared34 by the clipping approach wherein each and every
recognition unit along the dumbbell templated the formation of
a ring. We were ultimately limited, however, from extending
this protocol to the synthesis of higher-order polyrotaxanes on
account of the (i) poor solubility, and (ii) drop-off in yields
with increasing numbers of rings. Each of these limitations have
been remedied in the preparation of the R series of oligoro-
taxanes which are highly soluble and benefit from up to 99.9%
conversion efficiencies. These two features combined have allowed
us to access a monodisperse [20]rotaxane. Additionally, this
methodology appears to be conducive to the construction of
even higher-order, monodisperse [n]rotaxanes (n ≥ 50), on
account of positive cooperativity.
shifts (δ) for 13C spectra are referenced relative to the signal
from the carbon of the deuterated solvent. Abbreviations used
to define multiplicies are as follows: s = singlet; d = doublet; t =
triplet; q = quartet; m = multiplet; br = broad. High-resolution
mass spectra were measured on a Finnigan LCQ iontrap mass
spectrometer (HR-ESI).
Synthesis. 2,6-Pyridinedicarboxaldehyde47 (44) and tetra-
ethylene-glycol bis(2-amino-phenyl)ether48 (45) were prepared
according to literature procedures.
General Procedure A. A solution of 3-(3-aminopropyl-
amino)propan-1-ol (9) (1.0 equiv) in anhydrous EtOH (0.5 M)
was added to a solution of the requisite aldehyde (1.0 equiv) in
anhydrous EtOH (0.2 M), and the resulting solution was stirred
at room temperature for 16 h. NaBH4 (2.0 equiv) was added to
the reaction mixture, which was stirred for an additional 5 h,
before being concentrated in vacuo. The residue was taken up
in H2O (100 mL), extracted with EtOAc (3×), dried (MgSO4),
and filtered through a pad of Celite, and the filtrate was
concentrated in vacuo to provide the extended diamino alcohol
as a yellow oil that was used directly in the next step without
further purification.
General Procedure B. Di-tert-butyldicarbonate (2.0 equiv)
was added dropwise over 5 min to a solution of the diamino
alcohol (1.0 equiv of crude oil obtained in the previous step)
and NEt3 (4.0 equiv) in anhydrous CH2Cl2 (0.1 M) at 0 °C.
The resulting solution was warmed to room temperature
gradually and then stirred for 16 h before being concentrated in
vacuo. The residue was taken up in EtOAc, and the insoluble
salt was removed by filtration. The filtrate was concentration in
vacuo and the residue was purified by silica gel flash chroma-
tography to provide typically a yellow viscous oil.
CONCLUSION
■
The take-home message from the results described in this full
paper is contained in the data summarized in Tables 1 and 2
from which it may be concluded that there are “special forces”
at work during the template-directed syntheses of oligorotax-
anes in the R series (Table 1) that are not evident in the R′
series (Table 2). It would appear that if orthogonal recognition
motifs − in this case, hydrogen bonding orchestrating the
clipping of the rings onto the dumbbells with many equally and
strategically placed recognition sites augmented by multiple
extended stacking interactions by up to three arene units
per ring in the R series − are introduced into self-assembly
processes proceeding or accompanying acts of templation in
covalent synthesis, then molecules of high molecular weights
can be produced with awesome efficiencies − in this case, oligoro-
taxanes up to a [20]rotaxane in yields of 90%. In this R series of
oligorotaxanes, it would appear that progressively enhanced
molecular recognition and increased positive cooperativity
go hand-in-hand during chemical syntheses. The implication is
that a perfect alignment between noncovalent and dynamic
covalent synthesis endows template-directed protocols with the
ability to create monodisperse multifunctional macromolecules
in a remarkably efficient manner at ambient temperature.
10. Following general procedures A and B (based on 10.0 g
of 3,5-dimethoxy-benzaldehyde (1)), 22.9 g (79% over two
steps) of 10 was isolated (SiO2: Rf = 0.4, 50/50 v/v EtOAc in
1
hexanes) as clear viscous oil. H NMR (CDCl3, 500 MHz): δ
6.36 (br. s, 3H), 4.36 (br. s, 2H), 3.77 (s, 6H), 3.52 (br. s, 2H),
3.30−3.09 (m, 6H), 1.72 (br. s, 2H), 1.62 (br. s, 2H), 1.48 (s,
9H), 1.43 (s, 9H). 13C NMR (CDCl3, 125 MHz): δ 161.1,
156.0, 155.7, 105.7, 105.3, 99.0, 80.0, 58.3, 50.8, 50.3, 45.1,
44.6, 42.6, 30.7, 28.6, 28.5. MS (ESI): m/z Calcd for C25H43-
N2O7 [M + H]+: 483.31, found 483.39; Calcd for C25H42N2-
NaO7 [M + Na]+: 505.29, found 505.33.
EXPERIMENTAL SECTION
■
12. Following general procedures A and B (based on 8.50 g
of the aldehyde 16 in the reductive amination step), 8.30 g
(60% over two steps) of 12 was isolated (SiO2: Rf = 0.3, 70/30
Materials and Methods. Anhydrous dichloromethane
(CH2Cl2) and tetrahydrofuran (THF) were obtained from a
SC Water USA Glass Contour Seca Solvent System. Absolute
ethanol (EtOH), anhydrous triethylamine (NEt3), methanol
(MeOH), and dimethylsulfoxide (Me2SO) were purchased
from Aldrich and handled under an atmosphere of dry nitrogen.
CDCl3, CD2Cl2, CD3CN, and D2O were purchased from
Aldrich and used without further purification. All other reagents
were purchased from commercial sources and were employed
without further purification. All reactions were carried out
under an atmosphere of dry nitrogen in flame-dried flasks using
anhydrous solvents, unless indicated otherwise. Thin-layer
chromatography (TLC) was carried out using glass plates, pre-
coated with silica gel 60 with fluorescent indicator (Whatman
LK6F). The plates were inspected by UV light (254 nm) and/
or potassium permanganate stain. Column chromatography was
carried out by the flash technique using silica gel 60F (230 −
1
v/v EtOAc in hexanes) as a yellow viscous oil. H and 13C
spectra are provided in the SI. HR-MS (ESI): m/z Calcd for
C41H73N4O11 [M + H]+: 797.5270, found 797.5289; Calcd for
C41H76N5O11 [M + NH4]+: 814. 5536, found 814.5554; Calcd
for C41H72N4NaO11 [M + Na]+: 819.5090, found 819.5100.
13. Following general procedures A and B (based on 6.95 g
of the aldehyde 17 used in the reductive amination step), 6.10 g
(69% over two steps) of 13 was isolated (SiO2: Rf = 0.4, 70/30
1
v/v EtOAc in hexanes) as a yellow viscous oil. H and 13C
spectra are provided in the SI. HR-MS (ESI): m/z Calcd for
C57H103N6O15 [M + H]+: 1111.7476, found 1111.7453; Calcd
for C57H106N7O15 [M + NH4]+: 1128.7741, found 1128.7743;
Calcd for C57H102N6NaO15 [M + Na]+: 1133.7295, found
1133.7281.
1
400 mesh). H and 13C NMR spectra were recorded on a
14. Following general procedures A and B (based on 4.20 g
of the aldehyde 18 used in the reductive amination step), 2.81 g
(55% over two steps) of 14 was isolated (SiO2: Rf = 0.4, 70/30
Bruker ARX500 (500 MHz) spectrometer. The chemical shifts
1
(δ) for H spectra are given in ppm and referenced to the
1
residual proton signal of the deuterated solvent. The chemical
v/v EtOAc in hexanes) as a yellow viscous oil. H and 13C
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Article
spectra are provided in the SI. HR-MS (ESI): m/z Calcd for
C73H133N8O19 [M + H]+: 1425.9682, found 1425.9634; Calcd
for C73H132N8O19 [M + NH4]+: 1442.9947, found 1442.9931;
Calcd for C73H132N8NaO19 [M + Na]+: 1447.9501, found
1447.9508.
by adding a saturated solution of NH4PF6(aq). The precipitate
was filtered, washed with H2O, and air-dried, affording a white
powder.
2D·2PF6. Following general procedure D (based on 250 mg
of 1,3-diaminopropane (5)), 2.11 g (94%) of 2D·2PF6 was
1
General Procedure C. Oxalyl chloride (2.0 equiv per
alcohol) was added to a solution of Me2SO (4.0 equiv) in an-
hydrous CH2Cl2 (0.1 M) at −78 °C, and the resulting solution
was stirred for 10 min before a solution of the primary alcohol
(1.0 equiv, 0.5 M in anhydrous CH2Cl2) was added dropwise.
The reaction mixture was stirred for 20 min before adding
NEt3 (4.0 equiv). The reaction mixture was warmed to room
temperature gradually over the course of 2 h and allowed to stir
for a further 4 h, upon which the reaction was purged with a
stream of air for 30 min to reduce significantly the odor of
Me2S during purification steps. The reaction mixture was then
concentrated in vacuo. The residue was taken up in EtOAc, and
the insoluble salt was removed by filtration. The filtrate was
concentrated in vacuo and the residue was purified by silica gel
flash chromatography to provide typically a yellow viscous oil.
16. Following general procedure C (based on 10.0 g of 10),
7.9 g (79%) of 16 was isolated (SiO2: Rf 1= 0.4, 60/40 v/v
EtOAc in hexanes) as a yellow viscous oil. H NMR (CDCl3,
500 MHz): δ 9.75 (s, 1H), 6.36 (br. s, 3H), 4.36 (d, J = 15 Hz,
2H), 3.75 (s, 6H), 3.44 (br. s, 2H), 3.16 (br. s, 4H), 2.63 (br. s,
2H), 1.67 (br. s, 2H), 1.47 (br. s, 9H), 1.40 (br. s, 9H).
13C NMR (CDCl3, 125 MHz): δ 201.1, 161.0, 156.0, 155.6,
105.6, 105.2, 99.1, 79.9, 55.3, 50.8, 50.2, 45.9, 45.2, 44.5, 43.7,
43.4, 41.1, 28.5, 28.4. MS (ESI): m/z Calcd for C25H40N2O7
[M + H]+: 481.29, found 481.18.
17. Following general procedure C (based on 8.0 g of 12),
7.7 g (97%) of 17 was isolated (SiO2: RF 1= 0.3, 60/40 v/v
EtOAc in hexanes) as a yellow viscous oil. H and 13C NMR
spectra are provided in the SI. HR-MS (ESI): m/z Calcd for
C41H71N4O11 [M + H]+: 795.5114, found 795.5118; Calcd for
C41H70N4NaO11 [M + Na]+: 817.4933, found 817.4947.
18. Following general procedure C (based on 6.1 g of 13),
4.7 g (69%) of 18 was isolated (SiO2: RF 1= 0.4, 70/30 v/v
EtOAc in hexanes) as a yellow viscous oil. H and 13C NMR
spectra are provided in the SI. HR-MS (ESI): m/z Calcd for
C57H101N6O15 [M + H]+: 1109.7319, found 1109.7292; Calcd
for C57H104N7O15 [M + NH4]+: 1126.7585, found 1126.7589;
Calcd for C57H100N6NaO15 [M + Na]+: 1131.7139, found
1131.7135.
20. Following general procedure C (based on 2.8 g of 14),
2.2 g (79%) of 20 was isolated (SiO2: RF 1= 0.4, 70/30 v/v
EtOAc in hexanes) as a yellow viscous oil. H and 13C NMR
spectra are provided in the SI. HR-MS (ESI): m/z Calcd for
C73H131N8O19 [M + H]+: 1423.9525, found 1423.9548; Calcd
for C57H104N7O15 [M + NH4]+: 1126.7585, found 1126.7589;
Calcd for C57H100N6NaO15 [M + Na]+: 1131.7139, found
1131.7135.
General Procedure D. The requisite amine (1.0 equiv)
was added to a solution of 3,5-dimethoxybenzaldehyde (1) (2.0
equiv) in absolute EtOH (0.2 M) and stirred for 16 h at room
temperature. NaBH4 (4.0 equiv) was then added in one portion
and the solution was stirred for an additional 1 h before quench-
ing the reaction with Me2CO and concentrating in vacuo. The
residue was taken up in EtOAc, washed with H2O, dried
(MgSO4), and filtered through a pad of Celite, and the filtrate
was concentrated in vacuo. The residue was then dissolved
in concentrated HCl (12 N) and concentrated in vacuo. The
residue was dissolved in H2O and the product precipitated
obtained as a white powder. H NMR (CD3CN, 500 MHz): δ
6.61 (d, J = 2.2 Hz, 4H), 6.56 (t, J = 2.2 Hz, 2H), 4.08 (s, 4H),
3.80 (s, 12H), 3.05 (t, J = 7.6 Hz, 4H), 2.03 (q, J = 7.6 Hz, 2H).
13C NMR (CD3CN, 125 MHz): δ 161.0, 131.8, 107.5, 100.6,
54.9, 51.3, 44.1, 21.9. MS (ESI): m/z Calcd for C21H31N2O4
[M − HPF6−PF6]+: 375.23, found 375.27.
3D·3PF6. Following general procedure D (based on 250 mg
of bis(3-amino-propyl)amine (6)), 1.29 g (78%) of 3D·3PF6
was obtained as a white powder. 1H NMR (CD3CN, 500 MHz):
δ 6.60 (d, J = 2.2 Hz, 4H), 6.58 (t, J = 2.2 Hz, 2H), 4.11 (t, J =
5.4 Hz, 4H), 3.81 (s, 12H), 3.03 (m, 8H), 2.00 (q, J = 7.4 Hz,
4H). 13C NMR (CD3CN, 125 MHz): δ 161.0, 131.8, 107.5,
100.7, 54.9, 51.3, 44.7, 44.1, 21.9. MS (ESI): m/z Calcd for
C24H38N3O4 [M − 2HPF6−PF6]+: 432.29, found 432.30.
4D·4PF6. Following general procedure D (based on 250 mg
of N,N′-bis(3-aminopropyl)-1,3-propanediamine (8)), 1.00 g
1
(70%) of 4D·4PF6 was obtained as a white powder. H NMR
(CD3CN, 500 MHz): δ 6.94 (br s, 4H), 6.76 (br s, 4H), 6.61
(d, J = 2.0 Hz, 4H), 6.57 (t, J = 2.0 Hz, 2H), 4.11 (br s, 4H),
3.80 (s, 12H), 3.07 (br s, 12H), 2.03 (br s, 6H). 13C NMR
(CD3CN, 125 MHz): δ 162.0, 133.04, 108.6, 101.9, 56.1, 52.5,
46.0, 45.8, 45.3, 23.1. MS (ESI): m/z Calcd for C27H46F6N4O4P
[M − 2HPF6 − PF6]+: 635.31, found 635.13; Calcd for
C27H45N4O4 [M − 3HPF6−PF6]+: 489.34, found 489.36.
General Procedure E. A solution of bis(3-aminopropyl)-
amine (21) (1.0 equiv) in anhydrous EtOH (0.2 M) was added
to a solution of the requisite aldehyde (2.0 equiv) in anhydrous
EtOH (0.2 M) and the resulting solution was stirred at room
temperature for 16 h. NaBH4 (4.0 equiv) was added to the
reaction mixture, which was stirred for an additional 1 h before
quenching the reaction with Me2CO and concentrating in
vacuo. The residue was taken up in EtOAc, washed with H2O,
dried (MgSO4), filtered through a pad of Celite, and the filtrate
concentrated in vacuo. The residue was dissolved in CH2Cl2/
TFA (1/1, 0.1 M) and stirred for 24 h at room temperature.
The solvent was removed in vacuo and the residue was
dissolved in H2O and the product precipitated by adding a
saturated solution of NH4PF6(aq). The precipitate was filtered,
washed with H2O, and air-dried, affording a white powder.
7D·7PF6. Following general procedure E (based on 165 mg
of the aldehyde 16), 185 mg (79%) of 7D·7PF6 was isolated as
1
a white powder. H NMR (CD3CN, 500 MHz): δ 6.89 (br. s,
4H), 6.72 (br. s, 10H), 6.60 (d, J = 1.9 Hz, 4H), 6.57 (t, J =
1.9 Hz, 2H), 4.11 (t, J = 5.1 Hz, 4H), 3.81 (s, 12H), 3.07 (br. s,
24H), 2.02 (br. s, 12H). 13C (CD3CN, 125 MHz): δ 162.3,
133.0, 108.7, 101.9, 56.1, 52.6, 46.0, 45.9, 45.9, 45.3, 23.2.
HR-MS (ESI): m/z Calcd for C36H68F12N7O4P2 [M − 4HPF6−
PF6]+: 952.4611, found 952.4580; Calcd for C36H69F18N7O4P3
[M − 3HPF6−PF6]+: 1098.4331, found 1098.4307.
11D·11PF6. Following general procedure E (based on 740
mg of aldehyde 17), 511 mg (44%) of 11D·11PF6 was isolated
as a white powder. 1H NMR (CD3CN, 500 MHz): δ 6.93 (br. s,
4H), 6.74 (br. s, 18H), 6.60 (br. s, 4H), 6.57 (br. s, 2H), 4.11
(br. s, 4H), 3.80 (s, 12H), 3.07 (br. s, 40H), 2.02 (br. s, 10H).
13C (CD3CN, 125 MHz): δ 162.2, 133.0, 108.6, 101.9, 56.1, 52.5,
46.0, 45.9, 45.3, 23.1. HR-MS (ESI): m/z Calcd for C48H97-
F18N11O4P3 [M − 7HPF6−PF6]+: 1326.6645, found 1326.6637;
Calcd for C48H98F24N11O4P4 [M − 6HPF6−PF6]+: 1472.6365;
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found 1472.6367; Calcd for C48H99F30N11O4P5 [M − 5HPF6−
PF6]+: 1618.6085; found 1618.6100; Calcd for C48H100F36-
N11O4P6 [M − 4HPF6−PF6]+: 1764.5805; found 1764.5817;
Calcd for C48H101F42N11O4P7 [M − 3HPF6−PF6]+: 1910.5525;
found 1910.5537.
(s, 2H). 13C NMR (CD2Cl2, 125 MHz): δ 146.3, 140.2, 139.4,
132.2, 128.7, 128.3, 127.0, 119.0, 110.6, 64.7, 52.8, 52.5. MS
(ESI): m/z Calcd for C16H17N2O [M + H]+: 253.13, found
253.21.
31. Following general procedure B (based on 1.78 g of 30),
2.56 g (89%) of 31 was isolated (SiO2: Rf = 0.4, 2% MeOH in
CH2Cl2) as a viscous oil. 1H NMR (CD2Cl2, 500 MHz): δ 7.60
(d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 4H), 7.18 (br. s, 2H),
4.60 (s, 4H), 4.42 (br. s, 2H), 4.38 (br. s, 2H), 1.45 (br. s, 9H).
13C (CDCl3, 125 MHz): δ 155.8, 155.7, 147.2, 144.1, 143.8,
140.7, 136.6, 132.3, 128.2, 127.9, 127.5, 127.1, 126.8, 118.8,
110.8, 80.5, 64.3, 49.9, 49.7, 49.0, 28.1. MS (ESI): m/z Calc for
C21H25N2O3 [M + H]+: 353.19, found 353.66.
15D·15PF6. Following general procedure E (based on 235
mg of aldehyde 18), 140 mg (40%) of 15D·15PF6 was isolated
1
as a white powder. H NMR (CD3CN, 500 MHz): δ 6.94 (br.
s, 4H), 6.75 (br. s, 26H), 6.60 (br. s, 4H), 6.57 (br. s, 2H), 4.11
(br. s, 4H), 3.80 (s, 12H), 3.07 (br. s, 56H), 2.02 (br. s, 28H).
13C (CD3CN, 125 MHz): δ 162.2, 133.1, 108.7, 101.9, 56.1,
52.5, 46.0, 45.9, 45.3, 23.2. HR-MS (ESI): m/z Calcd for
C60H130F48N15O4P8 [M − 6HPF6−PF6]+: 2284.7559, found
2284.7616; Calcd for C60H129F42N15O4P7 [M − 7HPF6−PF6]+:
2284.7559, found 2284.7616; Calcd for C60H128F36N15O4P6
[M − 8HPF6−PF6]+: 1992. 8119, found 1992.8147; Calcd
for C60H127F30N15O4P5 [M − 9HPF6−PF6]+: 1846.8399, found
1846.8390; Calcd for C60H126F24N15O4P4 [M − 10HPF6−PF6]+:
1700.8679, found 1700.8638; Calcd for C60H125F18N15O4P3 [M −
11HPF6−PF6]+: 1554.8959, found 1554.9033.
19D·19PF6. Following general procedure E (based on 103 mg
of aldehyde 20), 81 mg (54%) of 19D·19PF6 was isolated as a
white powder. 1H NMR (CD3CN, 500 MHz): δ 7.08 (br. s, 4H),
6.87 (br. s, 34H), 6.60 (br. s, 4H), 6.58 (br. s, 2H), 4.10 (br. s,
4H), 3.80 (s, 12H), 3.06 (br. s, 72H), 2.02 (t, J = 6.8 Hz, 36H).
13C (CD3CN, 125 MHz): δ 162.2, 133.1, 108.7, 101.9, 56.1, 52.5,
32. A solution of 31 (2.56 g, 7.27 mmol) in THF (20 mL)
was added over the course of 5 min to a suspension of LiAlH4
(0.55 g, 14.5 mmol), in THF (60 mL) at 0 °C. The solution
was gradually warmed to room temperature over the course of
30 min and stirred for an additional 24 h. The reaction mixture
was quenched by cooling it to 0 °C and adding dropwise
H2O (0.56 mL), 15% NaOH(aq) (0.56 mL), and H2O (1.7 mL).
The resulting suspension was stirred for an additional 30 min,
filtered through a pad of Celite, and the filtrate was concen-
trated in vacuo. The residue was purified by silica gel flash
chromatography affording 1.76 g (68%) of 32 as a viscous oil
(SiO2: RF = 0.3, 94:6:0.5 CH2Cl2/MeOH/NH4OH). 1H NMR
(CD2Cl2, 500 MHz): δ 7.26 (d, J = 8.0 Hz, 2H), 7.21 (d, J =
8.0 Hz, 2H), 7.14 (br. s, 4H), 4.59 (s, 2H), 4.35 (br. s, 2H),
4.31 (br. s, 2H), 3.77 (s, 2H), 1.46 (s, 9H). 13C (CD2Cl2, 125
MHz): δ 155.9, 142.1, 140.6, 137.3, 136.7, 127.9, 127.7, 127.6,
127.3, 127.1, 79.9, 64.5, 49.4, 48.9, 45.9, 28.2. MS (ESI) m/z
Calcd for C21H29N2O3 [M + H]+: 357.22, found 357.31.
34. Following general procedure F (based on 3.30 g of
methyl 4-formylbenzoate (33)), 4.13 g (72%) of 34 was isolated
(SiO2: RF = 0.3, 95:5:0.5 CH2Cl2:MeOH:NH4OH) as a viscous
45.9, 45.3, 23.2. HR-MS (ESI): m/z Calcd for C102H168
-
F48N19O36 [M − 4CF3COO2]4+: 764.5315, found 764.4547.
28. A solution of methyl 4-cyanobenzoate (27) (5.00 g, 31.0
mmol) in THF (50 mL) was added over the course of 10 min
to a suspension of LiAlH4 (5.89 g, 155 mmol) in anhydrous
THF (200 mL) at 0 °C. The reaction mixture was stirred for an
additional 1 h before moving the flask to a 50 °C preheated oil
bath and stirred for 16 h. The reaction mixture was then cooled
to 0 °C and quenched by the slow addition of H2O (5.9 mL),
15% NaOH(aq) (5.9 mL), and H2O (17.7 mL). The resulting
precipitate was stirred for an additional 30 min, filtered through
a pad of Celite, rinsed with THF, and the filtrate concentrated
in vacuo. The residue was taken up in 1 M HCl (50 mL),
extracted with CH2Cl2 (1 × ), and the aqueous layer concen-
trated in vacuo. Me2CO (50 mL) was added to the crude solid
and the suspension was filtered affording 4.42 g (81%) of pure
28 as a white solid. 1H NMR (D2O, 500 MHz): δ 7.41 (s, 4H),
4.61 (s, 2H), 4.14 (s, 2H). 13C NMR (D2O, 125 MHz): δ
141.0, 131.9, 129.0, 128.0, 63.3, 42.7. MS (ESI): m/z Calcd for
C8H12NO [M + H]+: 138.09, found 138.34.
1
oil. H NMR (CDCl3, 500 MHz): δ 7.98 (d, J = 8.3 Hz, 2H),
7.39 (d, J = 8.0 Hz, 2H), 7.30 (br. s, 2H), 4.64 (s, 2H), 3.90 (s,
3H), 3.82 (s, 2H), 3.77 (s, 3H). 13C (CDCl3, 125 MHz):
δ 167.2, 145.6, 140.0, 139.3, 129.8, 128.9, 128.4, 128.1, 127.2,
65.0, 52.9, 52.7, 52.2. MS (ESI): m/z Calcd for C17H20NO3
[M + H]+: 286.14, found 286.24.
35. Following general procedure B (based on 3.99 g of 34),
5.22 g of 35 (97%) was isolated (RF = 0.4, 2% MeOH in
CH2Cl2) as a viscous oil. 1H NMR (CD2Cl2, 500 MHz): δ 7.95
(d, J = 8.2 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H), 7.25 (br. s, 2H),
7.17 (br. s, 2H), 4.63 (d, J = 5.4 Hz, 2H), 4.41 (br. s, 2H), 4.36
(br. s, 2H), 3.86 (s, 3H), 1.96 (t, J = 5.4 Hz, 1H), 1.44 (br. s,
9H). 13C (CD2Cl2, 125 MHz): δ 166.8, 155.8, 143.9, 143.7,
140.4, 137.2, 129.7, 129.2, 128.0, 127.6, 127.2, 80.2, 64.8, 52.0,
49.6, 49.0, 28.1. MS (ESI): m/z Calcd for C22H28NO5 [M + H]+:
386.20, found 386.40.
36. A solution of 35 (4.67 g, 12.1 mmol) in anhydrous THF
(40 mL) was added over the course of 10 min to a 1.0 M
solution of DIBAL in THF (48.5 mL, 48.5 mmol) at 0 °C. The
reaction mixture was gradually warmed to room temperature
and stirred for a total of 5 h before cooling back down to 0 °C
and quenching by the slow addition of H2O (1.9 mL), 15%
NaOH(aq) (1.9 mL), and H2O (4.9 mL). The resulting solution
was stirred for a further 30 min and then filtered through a pad
of Celite. The filtrate was concentrated in vacuo and the residue
was purified by silica gel flash chromatography to afford 3.05 g
(70%) of 36 as a viscous oil (SiO2: RF = 0.4, 4% MeOH in
CH2Cl2). 1H NMR (CD2Cl2, 500 MHz): δ 7.27 (d, J = 8.2 Hz,
4H), 7.16 (br. s, 4H), 4.61 (d, J = 5.5 Hz, 4H), 4.35 (br. s, 2H),
General Procedure F. NaHCO3 (1.5 equiv) was added to a
solution of [4-(amino-methyl)phenyl]methanol hydrochloride
(28) (1.0 equiv) and the appropriate aldehyde (1.0 equiv) in
anhydrous MeOH, and the resulting solution was stirred at
room temperature for 16 h. The reaction mixture was cooled
to 0 °C, NaBH4 (3.0 equiv) was added in portions, and the
reaction mixture was stirred for an additional 1 h. The reaction
was quenched by the addition of Me2CO and concentrated in
vacuo. The residue was taken up in EtOAc, washed with H2O,
brine, dried (MgSO4), and concentrated in vacuo. The residue
was purified by silica gel flash chromatography to provide
typically a viscous oil.
30. Following general procedure F (based on 2.70 g of
4-formylbenzonitrile (29)), 4.10 g (79%) of 30 was isolated
1
(SiO2: Rf = 0.4, 5% MeOH in CH2Cl2) as a viscous oil. H
NMR (CD2Cl2, 500 MHz): δ 7.60 (d, J = 8.2 Hz, 2H), 7.46 (d,
J = 8.2 Hz, 2H), 7.29 (s, 4H), 4.61 (s, 2H), 3.82 (s, 2H), 3.75
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4.31 (br. s, 2H), 2.15 (t, J = 5.5 Hz, 2H), 1.46 (s, 9H). 13C
(CD2Cl2, 125 MHz): δ 155.9, 140.3, 137.4, 128.0, 127.7, 80.0,
64.8, 49.4, 48.9, 28.2. MS (ESI): m/z Calcd for C21H28NO4
[M + H]+: 358.20, found 358.29.
37. Following general procedure C (based on 2.00 g of 36),
1.78 g (88%) of 37 was isolated as a viscous oil (SiO2: RF = 0.4,
60/40 v/v EtOAc in hexanes). 1H NMR (CDCl3, 500 MHz): δ
9.99 (s, 2H), 7.84 (d, J = 8.1 Hz, 4H), 7.35 (br. d, 4H), 4.53
(br. s, 2H), 4.42 (br. s, 2H), 1.46 (s, 9H). 13C (CDCl3, 125
MHz): δ 207.2, 191.9, 155.8, 145.0, 144.8, 135.8, 130.2, 128.4,
127.7, 81.0, 50.1, 49.8, 31.0, 28.4. MS (ESI): m/z Calcd for
C21H24NO4 [M + H]+: 354.17, found 354.23.
(br. s, 18H), 4.38 (br. s, 18H), 1.52 (br. s, 81H). 13C (CD2Cl2,
125 MHz): δ 155.9, 146.8, 140.8, 137.2, 128.0, 127.8, 127.0,
85.2, 78.0, 79.9, 64.4, 49.3, 48.8, 28.3, 27.2. MS (ESI): m/z
Calcd for C125H165N9O20 [M + 2H]2+: 1056.11, found 1056.34.
43. Following general procedure C (based on 310 mg of 41),
264 mg (85%) of 43 was isolated (SiO2: RF = 0.3, 60/40 v/v
1
EtOAc in hexanes) as a colorless oil. H NMR (CD2Cl2, 500
MHz): δ 9.96 (s, 2H), 7.81 (d, J = 8.5 Hz, 4H), 7.35 (br. s,
4H), 7.18 (br. s, 32H), 4.37 (br. s, 18H), 4.32 (br. s, 18H), 1.46
(br. s, 81H). 13C (CD2Cl2, 125 MHz): δ 206.5, 191.8, 191.8,
155.8, 137.4, 137.3, 136.9, 135.6, 129.9, 127.9, 127.8, 80.2, 79.9,
80.2, 79.9, 49.8, 49.2, 48.7, 30.7, 28.2. MS (ESI): m/z Calcd for
C
125H160N9O20 [M + 2H]2+: 1054.09, found 1054.71.
General Procedure G. A solution of amine 32 (2.0 equiv)
in anhydrous EtOH (0.2 M) was added to a solution of the
requisite dialdehyde (1.0 equiv) in anhydrous EtOH (0.2 M)
and the resulting reaction mixture was stirred at room tempera-
ture for 16 h. NaBH4 (2.0 equiv) was added to the reaction
mixture, which was stirred for an additional 5 h before being
concentrated in vacuo. The residue was dissolved in EtOAc,
washed with H2O, dried (MgSO4), and filtered through a pad
of Celite, and the filtrate was concentrated in vacuo to provide
the diol-terminated dumbbell which was purified by silica gel
flash chromatography to provide typically a viscous oil.
38. Following general procedure G (based on 2.80 g of 37),
3.45 g (85%) of 38 was isolated (SiO2: RF = 0.3, 95:5:0.5
General Procedure H. A solution of 3,5-dimethoxybenzyl-
amine (23) (2.0 equiv) in anhydrous EtOH (0.2 M) was added
to a solution of the requisite dialdehyde (1.0 equiv) in anhydrous
EtOH (0.2 M) and the resulting solution was stirred at room
temperature for 16 h. NaBH4 (2.0 equiv) was added to the
reaction mixture, which was stirred for an additional 5 h
before being concentrated in vacuo. The residue was taken up
in EtOAc, washed with H2O, dried (MgSO4), filtered through
a pad of Celite, and concentrated in vacuo. The residue was
dissolved in CH2Cl2/TFA (1/1, 0.1 M) and allowed to stir
for 24 h at room temperature. The solvent was removed in
vacuo, dissolved in an equal volume of H2O, and precipitated
by adding a saturated solution of NH4PF6(aq). The precipitate
was filtered, rinsed with H2O, and air-dried, affording a white
powder.
1
CH2Cl2/MeOH/NH4OH) as a viscous oil. H NMR (CD2Cl2,
500 MHz): δ 7.29−7.25 (m, 12H), 7.15 (br. s, 12H), 4.59 (s,
4H), 4.36 (br. s, 6H), 4.31 (br. s, 6H), 3.76 (s, 4H), 3.74 (s,
4H), 1.45 (s, 27H). 13C (CD2Cl2, 125 MHz): δ 155.8, 140.3,
139.4, 137.6, 136.9, 128.3, 127.9, 127.6, 127.1, 79.9, 79.8, 64.8,
52.8, 49.4, 49.0, 28.2. MS (ESI): m/z Calcd for C63H80N5O8
[M + H]+: 1034.60, found 1034.12.
2D′·2PF6. Following general procedure D (based on 100 mg
of p-xylylenediamine), 481 mg (90%) of 2D′·2PF6 was isolated
1
as a white powder. H NMR (CD3CN, 500 MHz): δ 7.53 (s,
4H), 7.19 (br. s, 4H), 6.61 (d, J = 2.2 Hz, 4H), 6.56 (t, J =
2.2 Hz, 2H), 4.24 (br. s, 4H), 4.16 (br. s, 4H), 3.79 (s, 12H). 13C
(CD3CN, 125 MHz): δ 162.2, 133.1, 132.8, 131.7, 108.8, 101.9,
56.1, 52.4, 51.6. HR-MS (ESI): m/z Calcd for C26H34F6N2O4P
[M − PF6]+: 583.2155, found 583.2156; Calcd for C26H33N2O4
[M − HPF6−PF6]+: 437.2435; found 437.2449
40. Following general procedure B (based on 3.32 g of 38),
3.03 g (77%) of 40 was isolated (SiO2: RF = 0.4, 4% MeOH in
1
CH2Cl2) as a colorless oil. H NMR (CD2Cl2, 500 MHz):
δ 7.29 (d, J = 8.2 Hz, 4H), 7.16 (br. s, 20 H), 4.63 (d, J =
5.4 Hz, 4H), 4.36 (br. s, 10H), 4.31 (br. s, 10H), 1.46 (s, 45H).
13C (CD2Cl2, 125 MHz): δ 155.8, 140.3, 139.4, 137.6, 136.9,
128.3, 127.9, 127.6, 127.1, 79.9, 79.8, 64.8, 52.8, 49.4, 49.9,
28.2. MS (ESI): m/z Calcd for C73H96N5O12 [M + H]+:
1234.71, found 1234.55.
3D′·3PF6. Following general procedure H (based on 153 mg
of 24), 245 mg (97%) of 3D′·3PF6 was isolated as a white
1
powder. H NMR (Me2SO-d6, 500 MHz): δ 9.27 (br. s, 6H),
7.55 (s, 8H), 6.66 (d, J = 2.2 Hz, 4H), 6.57 (t, J = 2.2 Hz, 2H),
4.20 (br. s, 8H), 4.18 (br. s, 4H), 4.10 (s, 12H). 13C (Me2SO-
d6, MHz): δ 160.7, 133.7, 132.5, 130.3, 107.8, 100.5, 55.4, 50.1,
49.8, 49.6. HR-MS (ESI): m/z Calcd for C34H44F12N3O4P2
[M − PF6]+: 848.2610, found 848.2623; Calcd for C34H43-
F6N3O4P [M − HPF6−PF6]+: 702.2890, found 702.2947; Calcd
for C34H42N3O4 [M − 2HPF6−PF6]+: 556.3170, found
556.3302.
7D′·7PF6. Following general procedure H (based on 98 mg
of 25), 136 mg (83%) of 7D′·7PF6 was isolated as a white solid.
1H NMR (CD3CN, 500 MHz): δ 9.03 (br. s, 14H), 7.52 (s,
24H), 6.62 (d, J = 2.2 Hz, 4H), 6.53 (t, J = 2.2 Hz, 2H), 4.13
(br. s, 24H), 4.03 (br. s, 4H), 3.77 (s, 12H). 13C (CD3CN, 125
MHz): δ 162.0, 131.4, 131.3, 108.7, 101.3, 56.1, 51.5, 51.3, 50.9.
HR-MS (ESI): m/z Calcd for C66H83F30N7O4P5 [M − HPF6−
PF6]+: 1762.4710, found 1762.4762; Calcd for C66H81F18-
N7O4P3 [M − 3HPF6 − PF6]+: 1470.5270, found 1470.5250;
Calcd for C66H80F12N7O4P2 [M − 4HPF6−PF6]+: 1324.5550,
found 1324.5520, Calcd for C66H79F6N7O4P [M − 5HPF6−
PF6]+: 1178.5830, found 1178.5791, Calcd for C66H78N7O4
[M − 6HPF6−PF6]+: 1032.6110, found 1032.6085, Calcd for
C66H84F30N7O4P5 [M − 2PF6]2+: 881.7392, found 881.7430.
42. Following general procedure C (based on 240 mg of 40),
177 mg (74%) of 42 was isolated (SiO2: RF = 0.2 60/40 → 75/
25 v/v EtOAc in hexanes) as a colorless oil. 1H NMR (CD2Cl2,
500 MHz): δ 9.96 (s, 2H), 7.81 (d, J = 8.2 Hz, 4H), 7.35 (br. s,
4H), 7.18 (br. s, 16H), 4.43−4.32 (m, 20H), 1.46 (s, 45H). 13
C
(CD2Cl2, 500 MHz): δ 191.8, 155.8, 137.4, 137.3, 136.6,
129.9, 128.0, 127.8, 80.3, 79.9, 49.8, 49.6, 49.2, 48.7, 28.2. MS
(ESI): m/z Calcd for C125H160N9O20 [M + H]+: 1054.09, found
1054.43.
39. Following general procedure G (based on 561 mg of
42), 735 mg (84%) of 39 was isolated (SiO2: RF = 0.4, 95:5:0.5
1
CH2Cl2/MeOH/NH4OH) as a viscous oil. H NMR (CDCl3,
500 MHz): δ 7.29 (m, 12H), 7.19 (m, 28H), 4.66 (s, 4H),
4.40 (s, 14H), 4.32 (s, 14H), 3.81 (s, 4H), 3.79 (s, 4H), 1.50 (s,
63H). 13C (CDCl3, 125 MHz): 156.1, 140.1, 139.1, 137.5,
137.1, 136.9, 128.5, 128.4, 128.3, 127.8, 127.4, 80.3, 80.2, 65.2,
53.6, 53.0, 49.3, 49.1, 48.7, 28.6. MS (ESI): m/z Calcd for
C
115H148N9O16 [M + H]+: 1911.10, found 1911.22.
41. Following general procedure B (based on 725 mg of 39),
705 mg (88%) of 41 was isolated (SiO2: RF = 0.4, 3% MeOH
1
in CH2Cl2) as a colorless oil. H NMR (CD2Cl2, 500 MHz):
δ 7.33 (d, J = 6.9 Hz, 4H), 7.24 (br. s, 36H), 4.63 (s, 4H), 4.43
5257
dx.doi.org/10.1021/ja2107564 | J. Am. Chem. Soc. 2012, 134, 5243−5261

Journal of the American Chemical Society
Article
11D′·11PF6. Following general procedure H (based on
42 mg of 26), 53 mg (53%) of 11D′·11PF6 was isolated as a
7.3 Hz, 4H), 6.51 (t, J = 7.3 Hz, 4H), 6.36 (t, J = 7.3 Hz, 4H),
6.29 (t, J = 7.3 Hz, 4H), 6.12 (d, J = 1.9 Hz, 4H), 5.91 (t, J =
1.9 Hz, 2H), 4.18−4.08 (m, 12H), 3.81−3.72 (m, 8H), 3.67
(br. s, 8H), 3.55−3.52 (m, 15H), 3.42−3.32 (m, 30H), 3.27 (s,
12H), 3.10−3.05 (m, 7H), 1.65 (br. s, 4H), 1.47 (br. s, 2H).
1
white powder. H NMR (CD3CN, 500 MHz): δ 9.89 (br. s,
22H), 7.51 (s, 40H), 6.64 (d, J = 2.2 Hz, 4H), 6.49 (t, J = 2.2 Hz,
2H), 4.15 (br. s, 34H), 4.12 (br. s, 4H), 4.05 (br. s, 4H), 3.74 (s,
12H). 13C (CD3CN, 125 MHz): δ 162.2, 133.3, 131.8, 108.7,
101.9, 56.1, 52.2. HR-MS (ESI): m/z Calcd for C98H118F24-
N11O4P4 [M − 6HPF6−PF6]+: 2092.7930, found 2092.7862,
Calcd for C98H116F12N11O4P2 [M − 8HPF6−PF6]+: 1800.8490,
found 1800.8455, Calcd for C98H115F6N11O4P [M − 9HPF6−
PF6]+: 1654.8770, found 1654.8726; Calcd for C98H114N11-
O4[M − 10HPF6−PF6]+: 1508.9050, found 1508.9052.
General Procedure I. In a typical procedure, the appro-
priate oligo-ammonium dumbbell (1.0 equiv) was added to a
solution of 2,6-pyridinedicarboxaldehyde (44) (n equiv, n =
number of ammonium recognition sites), and tetraethylenegly-
col bis(2-amino-phenyl)ether (45) (n equiv) in MeCN (0.5 M)
and stirred until equilibrium is reached (Table 1). Neat iPr2O
was layered on top of the MeCN solution until precipitation of
the oligorotaxane was complete. The precipitate was collected
by filtration, washed with iPr2O, and air-dried to afford the
oligorotaxane as a typically bright yellow powder.
2R·2PF6. Following general procedure I (based on 33 mg of
2D·2PF6), 78 mg (93%) of 2R·2PF6 was isolated as a yellow
powder. 1H NMR (CD3CN, 500 MHz): δ 9.40 (br. s, 4H), 8.30
(s, 4H), 7.75 (t, J = 7.8 Hz, 2H), 7.59 (d, J = 7.8 Hz, 4H), 7.20
(t, J = 8.0 Hz, 4H), 6.99 (d, J = 2 Hz, 4H), 6.72 (t, J = 8.0 Hz,
4H), 6.70 (d, J = 8.0 Hz, 4H), 6.19 (d, J = 2.2 Hz, 4H), 5.97 (t,
J = 2.2 Hz, 2H), 4.37 (t, J = 6.8 Hz, 4H), 4.24−4.21 (m, 8H),
3.82−3.78 (m, 4H), 3.74−3.70 (m, 4H), 3.58−3.37 (m, 20H),
3.25 (s, 12H), 1.9 (br. s, 2H). 13C NMR (CD3CN, 125 MHz):
δ 161.3, 160.0, 151.3, 151.1, 139.6, 138.8, 134.2, 129.6, 128.4,
121.0, 120.4, 112.1, 106.4, 100.2, 69.7, 69.6, 68.4, 67.8, 54.2,
50.8, 44.7, 23.1. HR-MS (ESI): m/z Calcd for C75H90F6N8O14P
[M − PF6]+: 1471.6217, found 1471.6220. Good quality single
crystals suitable for X-ray diffraction analysis were grown by
liquid−liquid diffusion of iPr2O into a solution of 2R·2PF6 in
CH2Cl2.
13C NMR: see SI. HR-MS (ESI): m/z Calcd for C135H164
-
F12N16O24P2 [M − 2PF6]2+: 1341.5689, found 1341.5625;
Calcd for C135H164F6N16O24P1 [M − 3PF6]3+: 846.0577, found
846.0558.
7R·7PF6. Following general procedure I (based on 25 mg of
7D·7PF6), 79 mg (94%) of 7R·7PF6 was isolated as a yellow
1
powder. H and 13C NMR spectra are provided in the SI.
HR-MS (ESI): m/z Calcd for C225H275F24N28O39P4 [M − 3PF6]3+:
1524.2982, found 1524.2985; Calcd for C225H275F18N28O39P3 [M −
4PF6]4+: 1106.9825, found 1106.9836; Calcd. for C225
-
H275F12N28O39P2 [M − 5PF6]5+: 856.5930, found 856.5903.
11R·11PF6. Following general procedure I (based on 15 mg
of 11D·11PF6), 45 mg (98%) of 11R·11PF6 was isolated as a
1
yellow powder. H and 13C NMR spectra are provided in the
SI. HR-MS (ESI): m/z Calcd for C245H423F42N44O59P7 [M −
4PF6]4+: 1786.2642, found 1786.2763; Calcd for C245H423F36-
N44O59P6 [M − 5PF6]5+: 1400.0184, found 1400.0153; Calcd
for C245H423F30N44O59P5 [M − 6PF6]6+: 1142.5212, found
1142.5061; Calcd for C245H423F24N44O59P4 [M − 7PF6]7+:
958.5946, found 958.5858.
15R·15PF6. Following general procedure I (based on 15 mg
of 15D·15PF6), 44 mg (93%) of 15R·15PF6 was isolated as a
1
yellow powder. H and 13C NMR spectra are provided in the
SI. HR-MS (ESI): m/z Calcd for C465H571F60N60O79P10 [M −
5PF6]5+: 1942.9006, found 1942.8957; Calcd for C465H571
-
F54N60O79P9 [M − 6PF6]6+: 1594.9230, found 1595.9068;
Calcd for C465H571F48N60O79P8 [M − 7PF6]7+: 1346.3676,
found 1346.3478; Calcd for C465H571F36N60O79P6 [M − 9PF6]9+:
1014.9604, found 1014.9535; Calcd for C465H571F30N60O79P5
[M − 10PF6]10+: 898.9679, found 898.9877.
19R·19PF6. Following general procedure I (based on 15 mg
of 19D·19PF6), 43 mg (90%) of 19R·19PF6 was isolated as a
1
yellow powder. H and 13C NMR spectra are provided in the
3R·3PF6. Following general procedure I (based on 43 mg of
3D·3PF6), 103 mg (90%) of 3R·3PF6 was isolated as a yellow
powder. 1H NMR (CD3CN, 500 MHz): δ 9.29 (br. s, 4H), 8.99
(br. s, 2H), 8.23 (s, 4H), 8.14 (s, 2H), 7.72 (t, J = 7.7 Hz, 2H),
7.54 (d, J = 7.7 Hz, 4H), 7.47 (d, J = 7.7 Hz, 2H), 7.36, (t, J =
7.7 Hz, 1H), 7.14−7.08 (m, 6H), 6.92 (d, J = 8.3 Hz, 4H), 6.78
(d, J = 8.3 Hz, 2H), 6.61 (d, J = 8.3 Hz, 4H), 6.56 (t, J = 8.3 Hz,
4H), 6.48 (d, J = 8.3 Hz, 2H), 6.39 (t, J = 8.3 Hz, 2H), 6.15 (d,
J = 2.3 Hz, 4H), 5.94 (t, J = 2.3 Hz, 2H), 4.22 (t, J = 7.0 Hz,
4H), 4.15−4.13 (m, 8H), 3.89 (t, J = 3.9 Hz, 4H), 3.76−3.32
(m, 36H), 3.33 (br. s, 4H), 3.18 (br. s, 4H), 3.26 (s, 12H), 1.72
(br. s, 4H). 13C NMR: see SI. HR-MS (ESI): m/z Calcd for
C105H127F12N12O19P2 [M − PF6]+: 2149.8622, found 2149.8608;
Calcd for C105H127F6N12O19P1 [M − 2PF6]2+: 1002.4490, found
1002.4507; Calcd for C105H127N12O19 [M − 3PF6]3+: 619.9780,
found 619.9806. X-ray quality single crystals were grown by
the vapor diffusion of tert-butylmethylether into a solution of
3R·3PF6 in MeOH.
SI. HR-MS (ESI): m/z Calcd for C585H719F72N76O99P12 [M −
7PF6]7+: 1734.1406, found 1734.1194; Calcd for C585H719
-
F66N76O99P11 [M − 8PF6]8+: 1499.2524, found 1499.1830,
Calcd for C585H719F60N76O99P10 [M − 9PF6]9+: 1316.5617,
found 1316.6811, Calcd for C585H719F54N76O99P9 [M − 10PF6]10+
:
1170.4090, found 1170.5047, Calcd for C585H719F48N76O99P8
[M − 11PF6]11+: 1050.8296, found 1050.6512.
2R′·2PF6. Following general procedure I (based on 25 mg of
2D′·2PF6), 50 mg (86%) of 2R′·2PF6 was isolated as a yellow
powder. 1H NMR (CD3CN, 500 MHz): δ 9.75 (br. s, 4H), 8.28
(s, 4H), 7.90 (t, J = 7.6 Hz, 2H), 7.54 (d, J = 7.6 Hz, 4H), 7.31
(t, J = 8.6 Hz, 4H), 7.11 (d, J = 7.6 Hz, 4H), 6.92 (t, J = 7.6 Hz,
4H), 6.71 (d, J = 7.6 Hz, 4H), 6.67 (s, 4H), 6.35 (d, J = 2.2 Hz,
4H), 5.97 (t, J = 2.2 Hz, 2H), 4.55 (t, J = 6.8 Hz, 4H), 4.40 −
4.37 (m, 8H), 4.27 (t, J = 6.8 Hz, 4H), 3.91 − 3.88 (m, 4H),
3.82 − 3.79 (m, 4H), 3.53 − 3.52 (m, 8H), 3.46 − 3.45 (m,
8H), 3.34 (s, 12H). 13C (CD3CN, 500 MHz): δ 162.1, 161.1,
152.7, 152.6, 141.1, 139.7, 135.3, 133.5, 130.2, 130.0, 129.6,
122.4, 121.7, 113.3, 108.3, 101.3, 71.4, 71.2, 70.1, 69.5, 55.5,
52.8, 52.1. HR-MS (ESI): m/z Calcd for C80H92F6N8O14P
[M − PF6]+: 1533.6369, found 1533.6300; Calcd for C80H91-
N8O14 [M − HPF6−PF6]+: 1387.6649, found 1387.6610; Calcd
for C80H92N8O14 [M − 2PF6]2+: 694.3361, found 694.3370.
3R′·3PF6. Following general procedure I (based on 25 mg of
3D′·3PF6), 44 mg (72%) of 3R′·3PF6 was isolated as a yellow
4R·4PF6. Following general procedure I (based on 53 mg of
4D·4PF6), 110 mg (88%) of 4R·4PF6 was isolated as a yellow
powder. 1H NMR (CD3CN, 500 MHz): δ 9.25 (br. s, 4H), 8.90
(br. s, 4H), 8.20 (s, 4H), 8.07 (s, 4H), 7.69 (t, J = 7.7 Hz, 2H),
7.52 (d, J = 7.7 Hz, 4H), 7.42 (d, J = 7.7 Hz, 4H), 7.32 (t, J =
7.7 Hz, 2H), 7.10 (t, J = 8.4 Hz, 4H), 7.04 (t, J = 8.4 Hz, 4H),
6.92 (d, J = 8.4 Hz, 4H), 6.70 (d, J = 8.4 Hz, 4H), 6.56 (d, J =
5258
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Journal of the American Chemical Society
Article
powder. 1H NMR (CD3CN, 500 MHz): δ 9.72 (br. s, 4H), 9.55
(br. s, 2H), 8.27 (s, 4H), 8.10 (s, 2H), 7.90 (t, J = 7.6 Hz, 2H),
7.74 (t, J = 7.6 Hz, 1H), 7.55 (d, J = 7.6 Hz, 4H), 7.36 (d, J =
7.6 Hz, 2H), 7.31−7.26 (m, 6H), 7.10 (d, J = 8.2 Hz, 4H), 7.04
(d, J = 8.2 Hz, 2H), 6.90 (t, J = 8.2 Hz, 4H), 6.83 (t, J = 8.2 Hz,
2H), 6.70 (d, J = 8.2 Hz, 4H), 6.65 (d, J = 8.2 Hz, 4H), 6.60 (d,
J = 8.2 Hz, 4H), 6.57 (d, J = 8.2 Hz, 2H), 6.35 (d, J = 2.2 hz,
4H), 5.96 (t, J = 2.2 Hz, 2H), 4.54 (t, J = 6.4 Hz, 4H), 4.39 −
4.20 (m, 16H), 3.92 − 3.71 (m, 16H), 3.54 − 3.37 (m, 24H),
3.34 (s, 12H). 13C NMR spectrum is provided in the SI. HR-MS
(ESI): m/z Calcd for C115H130F6N12O19P [M − HPF6−PF6]+:
2127.9212, found 2127.9460; Calcd for C115H131F6-
N12O19P [M − 2PF6]2+: 1064.4642, found 1064.4621; Calcd
for C115H130N12O19 [M − 3PF6]3+: 661.3212, found 661.3218.
7R′·7PF6. Following general procedure I (based on 20 mg of
7D′·7PF6), 41 mg (78%) of 7R′·7PF6 was isolated as a yellow
powder. 1H and 13C NMR spectra are provided in the SI. HR-MS
(ESI): m/z Calcd for C255H287F24N28O39P4 [M − 3PF6]3+:
1648.3285, found 1648.3337; Calcd for C255H287F18N28O39P3
REFERENCES
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[M − 4PF6]4+: 1200.0060, found 1200.0076; Calcd for C255
-
H
287F12N28O39P2 [M − 5PF6]5+: 931.0118, found 931.0120;
Calcd for C255H287F6N28O39P [M − 6PF6]6+: 751.6824, found
751.6797.
11R′·11PF6. Following general procedure I (based on 15 mg
of 11D′·11PF6) 32 mg (85%) of 11R′·11PF6 was isolated as a
1
yellow powder. H and 13C NMR spectra are provided in the
SI. HR-MS (ESI): m/z Calcd for C345H423F48N44O59P8 [M −
3PF6]3+: 2428.6190, found 2428.6179; Calcd for C345H423
-
F42N44O59P7 [M − 4PF6]4+: 1785.2231, found 1785.3202.
ASSOCIATED CONTENT
■
S
* Supporting Information
Detailed X-ray crystallographic analysis data and H and 13C
NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
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AUTHOR INFORMATION
Corresponding Author
stoddart@northwestern.edu; l.cronin@chem.gla.ac.uk
■
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We (M.E.B., C.V., R.A.S., D.C.F., and J.F.S.) at Northwestern
University acknowledge support from the Air Force Office
of Scientific Research (AFSOR) under the Multidisciplinary
Research Program of the University Research Initiative (MURI)
Award FA9550-07-1-0534 on “Bioinspired Supramolecular
Enzymatic Systems” and the National Science Foundation
(NSF) under the auspices of Award CHE-0924620. We also
acknowledge support by the Microelectronics Advanced Research
Corporation (MARCO) and its Focus Centre Research Program
(FCRP) on Functional Engineered NanoArchitectonics (FENA)
as well as support from the Non-Equilibrium Energy Research
Centre (NERC), which is an Energy Frontier Research Centre
(EFRC) funded by the U.S. Department of Energy, Office of
Basic Sciences (DOE-BES) under Award DE-SC0000989. J.F.S.
was supported by the WCU Program (NRF R-31-2008-000-
10055-0) funded by the Ministry of Education, Science and
Technology, Korea. The IM-MS work was supported by the
Univeristy of Glasgow and the EPSRC. L.C. thanks the Royal
Society/Wolfson Foundation for a merit award.
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were prevented by not being able to obtain stable ion-sprays.
(42) Data were collected at 100 K using a Bruker d8-APEX II CCD
diffractometer (Cu Kα radiation, λ = 1.54178 Å). Intensity data were
collected using ω and φ scans spinning at least a hemisphere of
reciprocal space for all structures (data were integrated using SAINT).
Absorption effects were collected on the basis of multiple equivalent
reflections (SADABS). Structures were solved by direct methods
(SHELXS) and refined by full-matrix least-squares against F2
(SHELXL). Hydrogen atoms were assigned riding isotropic displace-
ment parameters and constrained to idealized geometries. Crystallo-
graphic data (excluding structure factors) for the structures reported in
this article have been deposited with the Cambridge Crystallographic
Data Center as supplementary publication no. CCDC-826138
(2R·2PF6) and CCDC-826139 (3R·3PF6). Copies of the data can
be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1 EZ (fax: int. code (44) 1223 336−033; E-mail:
deposit@ccdc.cam.ac.uk).
(43) Crystal data for 2R·2PF6. C75H90F12N8O14P2·CH2Cl2·
(C3H7)2O. M = 1804.59, space group P1, triclinic, a = 13.4795(5),
b = 14.5068(4), c = 24.8176(7) Å, α = 85.849(2)°, β = 88.703(2)°,
γ = 62.846(2)°, V = 4306.4(2) Å3, Z = 2, ρcalc = 1.392 g cm−3, μ =
1.839 mm−1, 13912 reflections collected, 13912 observed independent
reflections (Rint = 0.0000) gave R = 0.0601 for I > 2σ(I) and wR2 =
0.1616.
(44) Crystal data for 3R·3PF6. C105H127F18N12O19P3. M = 2296.10,
space group P21/n, monoclinic, a = 16.3196(4), b = 31.1755(7), c =
22.7396(5) Å, α = 90.000(2)°, β = 95.673(2)°, γ = 90.000(2)°, V =
11512.6(5) Å3, Z = 4, ρcalc = 1.325 g·cm−3, μ = 1.320 mm−1, 78337
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