Periphery-Functionalized Porous Organic Cages

Article abstract of DOI:10.1002/chem.201603593

By synthesizing derivatives of a trans-1,2-diaminocyclohexane precursor, three new functionalized porous organic cages were prepared with different chemical functionalities on the cage periphery. The introduction of twelve methyl groups (CC16) resulted in

Full text of DOI:10.1002/chem.201603593

DOI: 10.1002/chem.201603593
Full Paper
&
Microporous Materials
Periphery-Functionalized Porous Organic Cages
Paul S. Reiss,[b] Marc A. Little,[a] Valentina Santolini,[c] Samantha Y. Chong,[a] Tom Hasell,[a]
Kim E. Jelfs,[c] Michael E. Briggs,*[a] and Andrew I. Cooper*[a]
Abstract: By synthesizing derivatives of a trans-1,2-diamino-
cyclohexane precursor, three new functionalized porous or-
ganic cages were prepared with different chemical function-
alities on the cage periphery. The introduction of twelve
methyl groups (CC16) resulted in frustration of the cage
packing mode, which more than doubled the surface area
compared to the parent cage, CC3. The analogous installa-
tion of twelve hydroxyl groups provided an imine cage
(CC17) that combines permanent porosity with the potential
for post-synthetic modification of the cage exterior. Finally,
the incorporation of bulky dihydroethanoanthracene groups
was found to direct self-assembly towards the formation of
a larger [8+12] cage, rather than the expected [4+6], cage
molecule (CC18). However, CC18 was found to be non-
porous, most likely due to cage collapse upon desolvation.
Introduction
Porous organic cages (POCs) such as the imine cage CC3[1]
(Scheme 1) have proved to be versatile functional materials.[2]
CC3 is formed by a cycloimination reaction between four mol-
ecules of triformylbenzene (TFB) and six molecules of homochi-
ral trans-1,2-diaminocyclohexane (CHDA, 1). This molecule crys-
tallizes with a window-to-window orientation that generates
a 3D diamondoid pore network that passes through the intrin-
sic cage voids.[3] As a result of its simple, high-yielding synthe-
sis, solution processability, and good physicochemical stabili-
ty,[4] CC3 has been used to form composite materials with en-
hanced separation properties:[5] for example, for the separation
of industrially relevant gas mixtures and chiral molecules.[6]
Other cage architectures based on boronate ester,[7] boroxine,[8]
and carbon–carbon[9] bond formation have broadened the
range of porous organic cage materials, and in some cases[10]
this has yielded materials with Brunauer–Emmett–Teller (BET)
surface areas that rival more established framework materials
such as metal-organic frameworks (MOFs), covalent-organic
frameworks (COFs), and amorphous polymer networks.
Scheme 1. Reaction Scheme for the synthesis of cages CC16 and CC17. The
[4+6] isomer of CC18 was not isolated; instead, a larger [8+12] cage was
formed (see below).
[a] Dr. M. A. Little, Dr. S. Y. Chong, T. Hasell, Dr. M. E. Briggs, Prof. A. I. Cooper
Department of Chemistry and Materials Innovation Factory
University of Liverpool, Crown Street, Liverpool, L69 7ZD (UK)
E-mail: mebriggs@liverpool.ac.uk
We first showed in 2009 how the surface functionality of
a series of isostructural imine cages could affect crystal packing
and hence porosity.[1] Until now, most variations on this theme
within our group have involved commercially-available vicinal
1,2-diamines.[11] An exception to this is our collaborative work
with James and colleagues on porous liquids,[12] which in-
volved the synthesis of various ethylene diamine derivatives
designed to decrease the melting point or increase the solubil-
ity of the resulting cages. More generally, the introduction of
reactive functionality on the periphery of shape-persistent
imine cages may expand their applications and allow new
aicooper@liverpool.ac.uk
[b] Dr. P. S. Reiss
Green Chemistry Centre of Excellence
Department of Chemistry, University of York
Heslington, York, YO10 5DD (UK)
[c] V. Santolini, Dr. K. E. Jelfs
Department of Chemistry, Imperial College London
South Kensington, London, SW7 2AZ (UK)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201603593.
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post-synthetic modification (PSM) strategies. For example, the
attachment of ligands onto the cage periphery could be used
to tune solubility, melting point, or crystal packing. Alternative-
ly, cages with reactive external functional groups might be
used as ‘pre-porous’ building blocks for extended MOFs or
COFs.[13] For imine POCs, most examples of PSM, so far, begin
with the reduction of the imine bond to the more stable but
flexible secondary amine, which is usually associated with the
collapse of the pore structure upon desolvation.[14] To our
knowledge, the only example of PSM on a shape-persistent
imine POC was reported by Schneider et al., who focused on
the etherification of internal hydroxyl groups.[15] This resulted
in a decrease in accessible surface area due to occupation of
the intrinsic cavity in the cage by alkyl chains. There is a need,
therefore, to develop new diamine building blocks for POCs
with richer external functionality.
amorphous solid, whereas crystalline CC16 is significantly
more porous than its structural analogue, CC3.
Results and Discussion
Diamine 2 was isolated as the hydrochloric acid salt following
reported procedures.[16] A solution of this hydrochloride salt
and triethylamine in methanol was layered on top of a solution
of TFB in CH2Cl2 and left standing at room temperature for 5
days. After this time, the homogeneous, green reaction mix-
ture was slowly concentrated under vacuum (<208C) to
remove the CH2Cl2 solvent and to induce the precipitation of
a white solid from the remaining methanol. The chirally pure
methyl-functionalized cage, CC16-R, was isolated by vacuum
filtration in a 79% yield. Analysis by MALDI-TOF mass spec-
trometry gave a molecular ion peak with m/z=1286, which
correlates to a [4+6] cage structure (Supporting Information,
Figure S14). Vial-in-vial crystallization of the cage from CH2Cl2-
ethyl acetate gave octahedral crystals, which were character-
ized by single crystal X-ray diffraction (SCXRD). CC16-R crystal-
lized in the cubic space group F4132, where the cage is disor-
dered over two positions, A (74% occupancy) and B (26% oc-
cupancy).
Three enantiomerically-pure vicinal 1,2-diamines derived
from CHDA were selected as candidates for POC synthesis.
(1R,2R,4R,5R)-4,5-Dimethylcyclohexane-1,2-diamine (2) introdu-
ces twelve methyl groups onto the exterior of CC3 (Figure 1a).
These methyl groups frustrate the cage packing but they are
In position A, the cages pack window-to-window (Fig-
ure 1b,d) as observed for the parent cage, CC3, in its a-
phase.[1] In comparison with CC3, the peripheral methyl groups
in CC16 frustrate the crystal packing and push the cages apart
to create a 19% increase in the unit cell volume occupied by
each cage molecule (1981 vs. 2351 ꢁ3, respectively), which re-
sults in the generation of additional extrinsic porosity. Howev-
er, unlike CC3, some structural disorder is observed in CC16,
presumably as a result of the less compact packing, whereby
26% of cages occupy position B and pack window-to-arene
(Figure 1c). These B sites are randomly distributed through the
crystal structure. As discussed below, this 26% of ‘misaligned’
cages does not prevent the material from being microporous.
The desolvated bulk CC16 material, which was isolated by pre-
cipitation from methanol, was also found to be crystalline by
powder X-ray diffraction (PXRD) analysis. The powder pattern
closely matched the pattern simulated from the SCXRD analy-
sis (Supporting Information, Figure S17). Scanning electron mi-
croscope (SEM) images obtained for bulk and recrystallized
samples also confirmed their crystalline nature, with both sam-
ples displaying octahedral crystal habits (Supporting Informa-
tion, Figure S19).
Figure 1. a) Molecular structure of CC16-R. The cage is disordered over two
positions and can pack window-to-window (b) or window-to-arene (c) in the
crystal. A diamondoid pore network structure exists in crystalline CC16-R be-
tween the cages that are packed window-to-window (d). Molecular structure
of CC17-R (e). This cage crystallizes as a solvate (f) (solvent molecules omit-
ted for clarity) that is not stable to removal of the solvent.
small enough to avoid penetration into the cavity of adjacent
cages. This results in additional extrinsic porosity between
cages. (1S,2S,4R,5R)-4,5-Diaminocyclohexane-1,2-diol (3) yields
a POC, CC17, which combines permanent porosity with the
potential for PSM by functionalization of the twelve peripheral
hydroxyl groups. The more bulky (11S,12S)-9,10-dihydro-9,10-
ethanoanthracene-11,12-diamine (4) was selected to further
frustrate the cage packing, and potentially to enhance extrinsic
porosity even more than we observed for CC16. Surprisingly,
however, this diamine formed a large [8+12] cage, CC18,
rather than the targeted [4+6] cage. This is the first example
of an [8+12] cage being isolated using TFB as a precursor.
CC18 is not stable to desolvation, and yields a non-porous
The incorporation of (1S,2S,4R,5R)-4,5-diaminocyclohexane-
1,2-diol (3) into a POC is a desirable target because the periph-
eral hydroxyl groups offer scope for synthetic diversification by
PSM. Diamine 3 was isolated as the hydrochloric acid salt fol-
lowing a literature procedure.[17] We screened a range of condi-
tions for the cage formation and found that the reaction of
the hydrochloride salt with TFB typically resulted in the forma-
tion of an insoluble precipitate, probably comprising oligomer-
ic by-products. However, using 100% methanol as the reaction
solvent appeared to slow the onset of precipitation, and after
4 days this afforded a mostly amorphous solid with small crys-
tals embedded in it. Structure solution for these crystals by
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SCXRD showed that the desired [4+6] cage was present in the
reaction mixture. The hydroxyl-functionalized cage, CC17-R,
crystallized in the chiral tetragonal space group P43212 as
a highly solvated material containing both methanol and
water molecules (Figure 1 f). The solvent volume of the reac-
tion mixture was reduced under vacuum (<208C) and the bulk
solid isolated by vacuum filtration. HPLC analysis showed the
reaction mixture to contain both cage and oligomeric by-prod-
ucts (Supporting Information, Figure S20). Pure CC17 could be
isolated as an amorphous white solid by preparative HPLC, al-
though the overall yield was poor (17%). Analysis by MALDI-
TOF mass spectrometry gave a molecular ion peak with m/z=
1310, which correlates with the [4+6] cage observed by
SCXRD (Supporting Information, Figure S15). The low reaction
yield is thought to be due to the poor solubility of kinetic in-
termediates, which precipitate before equilibrating to the de-
sired cage product. To improve solubility, it was decided to use
diamine 7, where the diols are protected, to form the cage
before deprotecting to afford the hydroxyl-decorated cage.
tert-Butyldimethylsilyl chloride (TBDMSCl) was identified as
a suitable protecting agent because it preferentially reacts
with alcohols over secondary amines and it is stable to the hy-
drogenation conditions required to remove the chiral auxili-
ary.[18] The reaction of the ethylbenzyl-protected diol diamine 5
with TBDMSCl in the presence of imidazole as a catalyst led to
6 in 89% isolated yield after purification by flash column chro-
matography.[19] The free diamine was generated by hydrogena-
tion and then reacted with TFB in CH2Cl2 (Scheme 2). After
7 days, a white precipitate was formed. To maximise the
yield, the volume of solvent was first reduced under vacuum
(<208C) and the solid was isolated by vacuum filtration to
afford amorphous CC19 in 77% yield. Analysis by 1H NMR
spectroscopy (Supporting Information, Figure S6) showed that
the TBDMS protecting group was retained in the final cage
product. Analysis by MALDI-TOF mass spectrometry gave a mo-
lecular ion peak with m/z=2680, which correlates to the ex-
pected [4+6] cage structure (Supporting Information, Fig-
ure S16). The hydroxyl groups were then regenerated by treat-
ment with tetrabutylammonium fluoride (TBAF).[20] Isolation of
the pure cage proved difficult: purification of the crude reac-
tion product by preparative HPLC was unsuccessful, with
impure material being isolated on each attempt. The cage
could be successfully recovered from the aqueous suspension
obtained after the work-up of the reaction mixture using a cen-
trifuge filter, followed by washing with water–acetonitrile
(95:5) and then with water. CC17 was finally isolated from the
aqueous suspension in 61% yield by freeze-drying. Analysis by
1H NMR spectroscopy showed it was the same material isolated
by the initial, lower yielding route (Supporting Information,
Figure S4). This demonstrates that the imine cage structure is
stable towards basic TBAF. PXRD analysis of the freeze-dried
sample showed it to be amorphous. Single crystals could be
isolated from several solvent systems, including trifluoroetha-
nol–THF and dimethylformamide–acetone. However, attempts
to desolvate CC17 through gentle heating led to a loss of crys-
tallinity in all cases.
Inspired by the effect that the peripheral methyl groups had
on the extrinsic porosity in CC16, we also explored bulky dia-
mine 4. Reactions between TFB and 4 in CH2Cl2 resulted in
consumption of the aldehyde and a mixture of imine products.
The reaction equilibrium could be shifted towards a single
product by adding a catalytic amount of trifluoroacetic acid.
Although other species were still observable under these con-
ditions, they were less prominent and could be removed by
swapping the reaction solvent to acetone, in which these im-
purities (but not the main cage product) were soluble. CC18
precipitated as a white solid and was isolated in 32% yield.
1
Analysis by H NMR spectroscopy confirmed the purity of the
cage, with sharp singlets at d=8.28 and 7.80 ppm confirming
the presence of imine and aromatic protons, respectively, in
a 1:1 ratio (Supporting Information, Figure S5). In addition, the
two singlets at d=4.09 and 3.75 ppm could be assigned to
the protons at the bridgehead positions. Analysis by MALDI-
TOF mass spectrometry was inconclusive, with only very weak
molecular ion peaks being observed. The bulk CC18 product
was isolated initially as an amorphous solid, as confirmed by
PXRD analysis. However, vial-in-vial crystallization of the cage
from CH2Cl2–acetone gave needle-like crystals that were solved
by SCXRD. CC18-S crystallized in the chiral trigonal space
group P321 as an [8+12] cage (Figure 2). CC18 is the first
[8+12] imine cage to be prepared using TFB as a precursor.
This may be due to a subtle change in the bond angles of the
diamine, 4. To probe this, the relative energies of the theoreti-
cal [4+6] cage and the observed [8+12] cage were examined
using gas-phase DFT calculations. Although these calculations
do not take into account any solvation effects, the results
Scheme 2. Reaction Scheme for the synthesis of CC17. Reaction conditions: (i) TBDMSCl, imidazole, CH2Cl2, rt, 89%. (ii) Pd(OH)2/C, H2, MeOH, rt, 99%. (iii) TFB,
CH2Cl2, rt, 77%. (iv) 1m TBAF, THF then 1M aq. NH4Cl, rt, 61%.
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This could be a consequence of hydrogen bonding between
the hydroxyl groups, which may promote a denser packing,
rather than generating additional extrinsic porosity. CC17 ad-
sorbs less CO2 than CC3, even though the polar hydroxyl
groups might be expected to promote the adsorption of acidic
CO2 molecules, as demonstrated previously by Schneider et al.,
who showed that capping interior hydroxyl groups with
methyl groups resulted in a reduction in CO2 uptake in their
cage material.[15] For CC17, it is possible that CO2 cannot gain
access to the polar groups. Nitrogen sorption measurements
for CC18 at 77 K and 1 bar mirrored the findings for other
large imine cages: it was non-porous to N2, consistent with the
collapse of the cage structure upon desolvation (Figure 3).
However, CC18 did adsorb small amounts of H2 and CO2, indi-
cating that the sterically demanding dihydroethanoanthracene
vertices may generate extrinsic pores of appropriate size to
allow the adsorption of smaller gas molecules.
Figure 2. Solvated CC18-S (crystal structure, solvent molecules removed for
clarity) (a) that collapses on desolvation (b) (grey, carbon; blue, nitrogen;
protons omitted for clarity).
showed that the larger [8+12] cage was energetically favoured
by 10 kJmolꢀ1 per [4+6] unit. Imine cages with an [8+12] stoi-
chiometry are rare and none has yet proven to be shape-per-
sistent enough to remain porous in the desolvated solid
state.[21] This is a result of the increased flexibility of larger
cages and the cumulative effect of the increased number of ro-
tatable bonds. Molecular dynamics simulations for CC18-S, in
the absence of solvent, showed that a collapsed cage confor-
mation (Figure 2b) is 65 kJmolꢀ1 lower in energy than the
open conformer found in the solvate. In keeping with this, the
crystalline CC18-S solvate quickly became amorphous when
left in air, presumably due to structural rearrangement of the
cage upon solvent loss (Supporting Information, Figure S18).
Nitrogen sorption measurements for CC16 at 77 K and 1 bar
showed
a Type I isotherm with a total gas uptake of
20.03 mmolgꢀ1 and an apparent BET surface area of
1023 m2 gꢀ1; that is, more than double the surface area ob-
served for highly crystalline CC3 (Table 1).[3] The increase in sur-
face area and overall N2 and H2 uptakes for CC16 is a conse-
quence of the peripheral methyl groups, which generate extra
accessible space between the cage molecules.
Figure 3. N2 adsorption isotherms for CC3 and enantiomerically pure CC16–
CC18 at 77 K and 1 bar. Adsorption and desorption isotherms are represent-
ed by closed and open symbols, respectively.
Table 1. Gas sorption values recorded at 1 bar for CC3 and enantiomeri-
cally pure CC16–CC18.
SABET [m2 gꢀ1
77 K
]
N2 [mmolgꢀ1
77 K
]
H2 [mmolgꢀ1
77 K
]
CO2 [mmolgꢀ1
273 K
]
Conclusion
CC3[3]
CC16
CC17
CC18
409
1023
423
10
4.50
20.03
7.06
5.00
5.92
4.15
2.61
2.01
2.00
1.81
1.03
Enantiomerically pure analogues of the POC precursor CHDA
were prepared and reacted with TFB to synthesise three new
cage molecules. CC16 was isolated as a phase-pure [4+6]
cage, and the introduction of methyl groups onto the cage
surface resulted in frustrated packing and higher porosity. By
contrast, the incorporation of bulky dihydroethanoanthracene
functionality led to the [8+12] cage, CC18, which is one of the
largest imine cages prepared to date, although subsequent de-
solvation led to cage collapse. The peripheral hydroxyl groups
in CC17 provide an imine cage that is amenable to further
modification, for example, to tune properties such as solubility
or melting point. Moreover, this tetrahedral cage, which has
twelve symmetrically disposed hydroxyl groups on its periph-
ery, might be a promising ‘porous organic ligand’ for the prep-
aration of metal-organic or covalent organic frameworks.[13a]
0.45
Previously, Schneider et al. investigated the influence of pe-
ripheral groups on the porosity of POCs by incorporating sali-
cyldialdehydes with a range of substituents at the 4-position.[22]
They found that bulkiness in the peripheral groups can be ne-
glected when the POCs are amorphous because the porosity is
dictated by the size of the intrinsic cavity within the cage.
However, in the crystalline state, more sterically demanding
peripheral substituents imparted a lower accessible surface
area. Despite becoming amorphous upon desolvation, hydrox-
yl-substituted CC17 displayed
a
total N2 uptake of
7.06 mmolgꢀ1 and an apparent BET surface area of 423 m2 gꢀ1
(Table 1). This surface area is lower than for amorphous CC3.[3]
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Preparative HPLC was conducted using a Shimadzu Prominence
Preparative HPLC system. The column used for the purification of
crude product samples of CC17 was Syncronis C8, 150ꢂ30 mm,
5 mm (SN 10159851, Lot 12105). The mobile phase was methanol–
Experimental Section
General
Solution 1H and 13C NMR spectra were recorded at 400.13 and
100.6 MHz, respectively, using a Bruker Avance 400 NMR spectrom-
eter. Chemical shifts are reported in ppm (d) with reference to the
internal residual protonated species of the deuterated solvent
used for 1H and 13C analysis. IR spectra were recorded using
a Bruker Tensor 27 FT-IR spectrometer with Quest ATR (diamond
crystal puck) attachment running Opus 6.5 software. Samples were
water (10:90 to 90:10 over 9 min) at a flow rate of 35 mLminꢀ1
.
The injection volume was 600 mL and the sample concentration
was ca. 20 mgmLꢀ1 in DMSO–methanol (2:1). The column oven
temperature was set to 308C. Detection for HPLC analysis was con-
ducted at 254 nm.
Single crystal X-ray data for CC16-R was measured at beamline I19,
Diamond Light Source, Didcot, UK using silicon double crystal
monochromated synchrotron radiation (l=0.6889 ꢁ, Rigaku
Saturn724+ detector);[23] for CC17-R on a Bruker D8 Venture Ad-
vance diffractometer equipped with an ImS microfocus source (Cu–
Ka radiation, l=1.54178 ꢁ, Kappa 4-circle goniometer,
PHOTON100 CMOS detector); and for CC18-S at beamline 11.3.1,
Advanced Light Source, Berkeley, USA using silicon monochromat-
ed synchrotron radiation (l=0.7749 ꢁ, PHOTON100 CMOS detec-
tor). Solvated single crystals, isolated from the crystallization sol-
vent, were immersed in protective oil, mounted on a MiTeGen
loop, and flash cooled under a dry nitrogen gas flow. Empirical ab-
sorption corrections, using the multi-scan method, were performed
with the program SADABS.[24] Structures were solved with
SHELXD,[25] SHELXT,[26] or by direct methods using SHELXS,[27] and
analysed as dry powders for 16 scans with a resolution of 4 cmꢀ1
Spectra were recorded in transmission mode.
.
CI mass spectra were recorded using an Agilent Q-TOF 7201. ESI
mass spectra were recorded using a Micromass LCT-MS. MALDI-
TOF MS was conducted using an AXIMA Confidence MALDI MS
(Shimadzu Biotech) fitted with a 50 Hz N2 laser. A 10:1 ratio of
matrix/sample was dissolved in THF (10 mgmLꢀ1) and this was
drop coated onto the microtitre plate before analysis. For CC16,
the matrix used was dithranol. For CC17 and CC19, the matrix
used was trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]-
malononitrile (DCTB).
CHN analysis was conducted using a Thermo FlashEA 1112 Elemen-
tal Analyser. Samples were analysed as dry powders and the data
was processed using dedicated elemental analysis software.
2
reined by full-matrix least squares on jFj by SHELXL,[28] interfaced
through OLEX2.[29] CCDC 1481844, 1481845, and 1481846 for CC16,
CC17, and CC18, respectively, contain the supplementary crystallo-
graphic data for this paper. These data are provided free of charge
by The Cambridge Crystallographic Data Centre.
PXRD data for enantiomerically-pure CC16 were collected using
a PANalytical X’Pert PRO HTS X-ray diffractometer with Cu–Ka1 radi-
ation. Samples were ground and mounted as a loose powder onto
transparent film, with data collected in the range 48ꢁ2qꢁ508
with a step size of 0.0138 over 1 h.
The [4+6] versus [8+12] molecular mass of CC18 was initially eval-
uated using high temperature molecular dynamics simulations in
order to explore the potential energy surfaces and to identify the
lowest energy conformers. Molecular dynamics simulations were
performed with the Macromodel Software (Schrçdinger PLC) and
the recently released OPLS3 force field.[30] The calculations were
run at 1000 K for 100 ns with a time step of 1 fs, and each involved
the sampling of 10,000 structures that were geometry optimized at
each step of the simulation. Both open and collapsed conformers
for [4+6] and [8+12] were re-optimized with DFT methods in
order to rank the structures according to their energy with more
accurate methods and therefore to predict the most likely reaction
outcome. The four structures were optimized with the CP2K soft-
ware[31] using the PBE DFT functional, combined with a TZVP-
MOLOPT basis set[32] in combination with Geodecker–Teter–Hutter
pseudopotentials, a plane-wave cut-off of 350 Ry, and Grimme’s D3
dispersion correction.[33]
For enantiomerically-pure CC18, as the cage was potentially sensi-
tive to guest loss, crystals were ground and dispersed in a minimal
volume of crystallization solvent before loading into borosilicate
glass capillaries. Laboratory PXRD data were collected from the
samples in transmission geometry on a PANalytical Empyrean dif-
fractometer producing Cu–Ka1 radiation and equipped with an X-
ray focussing mirror, using a PIXceL3D detector operating in 1D
scanning mode. Powder data were collected in the range 28ꢁ2qꢁ
408 in steps of 0.0138 over 1 h. This program was cycled to monitor
any structural changes over a period of 4 h. In the absence of sig-
nificant changes in diffraction, individual patterns were summed to
generate a cumulative profile with improved counting statistics.
The temperature of the capillary was controlled using an Oxford
Cryosystems 700 Series Cryostream Plus.
High resolution imaging of the crystal morphology of CC16 was
achieved using a Hitachi S-4800 Cold Field Emission Scanning Elec-
tron Microscope (FE-SEM). Scanning-mode samples were prepared
by depositing dry crystals on 15 mm Hitachi M4 aluminium stubs
using an adhesive high-purity carbon tab before coating with
a 2 nm layer of gold using an Emitech K550X automated sputter
coater. Imaging was conducted at a working distance of 8 mm and
a working voltage of 3 kV using a mix of upper and lower secon-
dary electron detectors. The FE-SEM measurement scale bar was
calibrated using certified SIRA calibration standards.
Surface areas for enantiomerically-pure CC16–CC18 were mea-
sured by N2 sorption at 77 K and 1 bar. Powder samples were de-
gassed offline at 373 K for 15 h under dynamic vacuum (10ꢀ5 bar)
before analysis, followed by degassing on the analysis port under
vacuum, also at 373 K. Isotherms were measured using Micromerit-
ics 2020 or 2420 volumetric adsorption analysers. N2 and H2 iso-
therms were maintained at 77 K by liquid nitrogen cooling. Higher
temperature isotherms for CO2 (273 K) required a circulating water
chiller/heater to maintain the temperature. All measurements were
carried out using high purity gases supplied by BOC gases: N2
(N5.0: 99.999%); H2 (L05410 A) and CO2 (both N5.5: 99.9995%).
Compounds 2,[16] 3, and 5[17] were synthesized according to previ-
ously reported procedures. 4, 20% palladium hydroxide on carbon
and tert-butyldimethylsilyl chloride were purchased from TCI–UK.
Trifluoroacetic acid was purchased from Alfa Aesar. TFB was pur-
chased from Manchester Organics. Triethylamine was purchased
from Alfa Aesar and distilled prior to use. All other reagents were
Analytical HPLC was conducted using a Dionex Ultimate 3000
HPLC system. The column used for the analysis of both crude and
purified product samples of CC17 was Syncronis C8, 150ꢂ4.6 mm,
3 mm (SN 10136940, Lot 12459). The mobile phase was methanol–
water (10:90 to 90:10 over 27 min) at a flow rate of 0.5 mLminꢀ1
The injection volume was 2 mL and the sample concentration was
ca. 1 mgmLꢀ1 in DMSO. The column oven temperature was set to
308C. Detection for HPLC analysis was conducted at 254 nm.
.
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purchased from Sigma Aldrich and all reagents, with the exception
of triethylamine, were used as received.
(40 mL) was added triethylamine (0.37 g, 3.65 mmol) and the re-
sulting solution was stirred for 20 min. After this time, the solution
was layered slowly using a Pasteur pipette onto a solution of TFB
(0.19 g, 1.17 mmol) in methanol (40 mL). The reaction mixture was
sealed and left standing for 4 d. After this time, both amorphous
and crystalline precipitate was observable. The reaction mixture
was concentrated to dryness under a nitrogen flow, at which point
the crude solid was washed with a CH2Cl2–methanol mixture (95:5,
2ꢂ10 mL), isolated by filtration and then dried under vacuum to
yield the crude product as a brown solid (0.36 g). Separate samples
were combined, with the crude product dissolved in DMSO–meth-
anol (2:1, 24 mL), and the resulting solution was syringe filtered
(0.45 mm) and purified by preparative HPLC. The product-contain-
ing fractions were concentrated to dryness under vacuum to yield
CC17 as a powdery white solid (0.11 g, 0.08 mmol, 17%). Route
2.[20] With stirring, TBAF (1m in THF, 0.90 mL, 0.90 mmol) was
added dropwise to a cooled solution of CC19 (0.10 g, 0.04 mmol)
in THF (12 mL). After stirring at room temperature for 24 h, the re-
action mixture was quenched with 1m NH4Cl (1.5 mL) and the THF
was removed under vacuum (<208C) to leave a white suspension.
This was transferred to a Corningꢃ Spin-Xꢃ UF centrifugal concen-
trator (30 K MWCO) and the white precipitate was successively
washed with a water–acetonitrile mixture (95:5, 12 mL) and water
(3ꢂ12 mL). The collected white solid was suspended in a minimum
amount of water and then freeze-dried for 2 d to yield CC17 as
Synthetic procedures
(1R,2R,4S,5S)-4,5-Bis((tert-butyldimethylsilyl)oxy)-N,N’-bis((S)-1-
phenylethyl)cyclohexane-1,2-diamine (6):[19] A solution of tert-bu-
tyldimethylsilyl chloride (0.86 g, 5.71 mmol) in CH2Cl2 (2 mL) was
added to a cooled solution of 5 (0.81 g, 2.28 mmol) and imidazole
(0.39 g, 5.73 mmol) in CH2Cl2 (6 mL). The reaction mixture was
stirred at room temperature for 16 h. After this time, water (8 mL)
was added. The organic phase was isolated and the aqueous
phase extracted with CH2Cl2 (3ꢂ15 mL). The organic phases were
combined and washed with water (15 mL) and a saturated solution
of sodium hydrogen carbonate (15 mL), dried over anhydrous mag-
nesium sulfate, filtered, and the filtrate concentrated to dryness
under vacuum to afford the crude product as a white solid. This
was purified by column chromatography (hexane/ethyl acetate,
93:7 to 50:50) to yield 6 as a white solid (1.18 g, 2.02 mmol, 89%).
1H NMR (400 MHz, CDCl3,) d=7.34–7.21 (m, 10H, ArH), 3.80 (q, 2H,
Ph-CH), 3.19 (m, 2H, CHꢀO), 2.09 (m, 2H, CH2), 1.95 (m, 2H, CHꢀ
NH), 1.33 (d, 6H, CH3), 0.91 (m, 2H, CH2), 0.85 (s, 18H, CH3), 0.01 (s,
6H, CH3), 0.00 ppm (s, 6H, CH3); 13C NMR (100.6 MHz, CDCl3) d=
145.6, 128.6, 127.1, 126.8, 74.2, 55.7, 54.9, 37.7, 26.2, 25.4, 18.2,
ꢀ3.9, ꢀ4.6 ppm; FT-IR (neat): v˜ =2956, 2927, 2853, 1461, 1360,
1251, 1099, 1063, 1055, 923 cmꢀ1; MS (CI): m/z: 583 [M+H]+.
1
a powdery white solid (0.03 g, 0.02 mmol, 61%). H NMR (400 MHz,
[D6]DMSO) d=8.23 (s, 12H, CH=N), 7.82 (s, 12H, ArH), 4.79 (br. s,
12H, CHꢀOH), 3.44 (m, 24H, CHꢀN + CHꢀOH), 1.68 ppm (m, 24H,
CH2); 13C NMR (100.6 MHz, [D7]DMF,) d=160.3, 137.9, 130.1, 74.3,
73.6, 40.2 ppm; FT-IR (neat): v˜ =3358, 2929, 2866, 1646, 1449, 1378,
1325, 1160, 1110, 1037, 1007, 919, 696 cmꢀ1; MS (MALDI-TOF,
DCTB): m/z: 1310 [M+H]+; elemental analysis calcd (%) for
C72H84N12O12: C 66.04, H 6.47, N 12.84; found: C 59.64, H 6.63, N
11.15.
(1R,2R,4S,5S)-4,5-Bis((tert-butyldimethylsilyl)oxy)cyclohexane-
1,2-diamine (7): To an autoclave under a nitrogen atmosphere was
added 20% palladium hydroxide on carbon (0.81 g), 6 (2.00 g,
3.43 mmol) and methanol (145 mL). The reaction mixture was
stirred vigorously at room temperature under hydrogen at 10 atm
pressure for 72 h. After this time, the reaction mixture was filtered
through Whatman Microfibre GF/F filter paper and the autoclave
rinsed with methanol. The rinses and filtrate were combined and
concentrated to dryness under vacuum to yield 7 as a colourless
CC18: A solution of 4 (0.25 g, 1.06 mmol) in CH2Cl2 (20 mL) was
added slowly using a Pasteur pipette onto a solution of TFB
(0.11 g, 0.68 mmol) and a catalytic amount of trifluoroacetic acid in
CH2Cl2 (20 mL). The reaction mixture was sealed and left standing
at room temperature for 7 d. After this time, a small amount of
white precipitate was observable. With stirring, the reaction mix-
ture was diluted with CH2Cl2 (40 mL) and quenched with excess
sodium hydrogen carbonate. The suspension was filtered under
vacuum and the filtrate reduced to a volume of 10 mL under
vacuum (<208C). Acetone (20 mL) was added and the reaction
mixture stirred under ice for 20 min to leave a white turbid solu-
tion. This was reduced to a volume of 10 mL under vacuum (<
208C) and the precipitate was isolated by vacuum filtration,
washed with cold acetone (2ꢂ5 mL) and dried under vacuum to
yield CC18 as a powdery white solid (0.10 g, 0.03 mmol, 32%).
1H NMR (400 MHz, CDCl3) d=8.28 (s, 24H, CH=N), 7.80 (s, 24H,
ArH), 7.38–7.15 (m, 96H, ArH), 4.09 (s, 24H, ArꢀCH), 3.75 ppm (s,
24H, CHꢀN); 13C NMR (100.6 MHz, CDCl3) d=161.6, 142.4, 140.5,
136.9, 129.7, 126.2, 126.1, 125.7, 123.8, 77.4, 53.9 ppm; FT-IR (neat):
v˜ =3021, 2944, 2856, 1703, 1637, 1595, 1458, 1153, 1116, 1024, 965,
882 cmꢀ1; elemental analysis calcd. (%) for C264H192N24: C 85.69, H
5.23, N 9.08; found: C 79.64, H 4.91, N 8.17.
1
oil (1.27 g, 3.39 mmol, 99%). H NMR (400 MHz, CDCl3) d=3.48 (m,
2H, CHꢀO), 2.35 (m, 2H, CH2), 1.99 (m, 2H, CHꢀNH2), 1.26 (m, 2H,
CH2), 0.89 (s, 18H, CH3), 0.08 (s, 6H, CH3), 0.06 ppm (s, 6H, CH3);
13C NMR (100.6 MHz, CDCl3) d=74.5, 55.2, 41.1, 26.2, 18.2, ꢀ3.8,
ꢀ4.6 ppm; FT-IR (neat): v˜ =2952, 2928, 2856, 1578, 1472, 1388,
1360, 1250, 1104, 1065, 1005 cmꢀ1; MS (ESI): m/z: 375 [M+H]+.
CC16: To a solution of (1R,2R,4R,5R)-4,5-dimethylcyclohexane-1,2-
diamine dihydrochloride (0.58 g, 2.70 mmol) in methanol (15 mL)
was added triethylamine (0.55 g, 5.44 mmol) and the resulting so-
lution was stirred for 20 min. After this time, the solution was lay-
ered slowly using a Pasteur pipette onto a suspension of TFB
(0.28 g, 1.73 mmol) in CH2Cl2 (12 mL). The reaction mixture was
sealed and left standing at room temperature for 5 d. After this
time, the volume of the homogeneous, green reaction mixture was
reduced under vacuum (<208C) until precipitation was induced.
The white precipitate was isolated by vacuum filtration, washed
with methanol (2ꢂ5 mL) and dried under vacuum to yield CC16 as
1
a powdery white solid (0.44 g, 0.34 mmol, 79%). H NMR (400 MHz,
CDCl3) d=8.16 (s, 12H, CH=N), 7.89 (s, 12H, ArH), 3.54 (m, 12H,
CHꢀN), 2.12 (m, 12H, CH2), 1.83 (m, 12H, CH2), 1.30 (m, 12H, CHꢀ
CH3), 1.19 ppm (d, 36H, CH3); 13C NMR (100.6 MHz, CDCl3) d=
159.6, 136.0, 129.5, 69.4, 32.8, 32.7, 19.5 ppm; FT-IR (neat): v˜ =2960,
2922, 2875, 1647, 1457, 1376, 1156, 1099, 1001, 961 cmꢀ1; MS
(MALDI-TOF, dithranol): m/z: 1286 [M+H]+; elemental analysis
calcd. (%) for C84H108N12: C 78.46, H 8.47, N 13.07; found: C 73.62, H
8.33, N 12.17.
CC19: A solution of 7 (0.64 g, 1.71 mmol) in CH2Cl2 (30 mL) was
added slowly via Pasteur pipette onto a solution of TFB (0.18 g,
1.11 mmol) in CH2Cl2 (35 mL) and left standing at room tempera-
ture for 7 d. After this time, a white precipitate was observable.
The volume of CH2Cl2 was reduced by half under vacuum (<208C)
and the precipitate isolated by vacuum filtration, washed with
methanol (2ꢂ10 mL) and dried under vacuum to yield CC18 as
CC17: Route 1. To a suspension of (1S,2S,4R,5R)-4,5-diaminocyclo-
hexane-1,2-diol dihydrochloride (0.40 g, 1.83 mmol) in methanol
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[11] a) M. J. Bojdys, M. E. Briggs, J. T. A. Jones, D. J. Adams, S. Y. Chong, M.
Schmidtmann, A. I. Cooper, J. Am. Chem. Soc. 2011, 133, 16566–16571;
b) T. Hasell, J. L. Culshaw, S. Y. Chong, M. Schmidtmann, M. A. Little, K. E.
Jelfs, E. O. Pyzer-Knapp, H. Shepherd, D. J. Adams, G. M. Day, A. I.
Cooper, J. Am. Chem. Soc. 2014, 136, 1438–1448.
[12] a) N. Giri, C. E. Davidson, G. Melaugh, M. G. Del Pꢄpolo, J. T. A. Jones, T.
Hasell, A. I. Cooper, P. N. Horton, M. B. Hursthouse, S. L. James, Chem.
Sci. 2012, 3, 2153; b) G. Melaugh, N. Giri, C. E. Davidson, S. L. James,
M. G. Del Pꢄpolo, Phys. Chem. Chem. Phys. 2014, 16, 9422–9431; c) N.
Giri, M. G. Del Pꢄpolo, G. Melaugh, R. L. Greenaway, K. Rꢅtzke, T. Ko-
schine, L. Pison, M. F. C. Gomes, A. I. Cooper, S. L. James, Nature 2015,
527, 216–220.
a powdery white solid (0.57 g, 0.21 mmol, 77%). H NMR (400 MHz,
CDCl3) d=8.15 (s, 12H, CH=N), 7.93 (s, 12H, ArH), 3.68 (m, 12H,
CHꢀO), 3.37 (m, 12H, CHꢀN), 1.79 (m, 24H, CH2), 0.87 (s, 108H,
CH3), 0.09 (s, 36H, CH3), 0.07 ppm (s, 36H, CH3); 13C NMR
(100.6 MHz, CDCl3) d=159.9, 136.5, 130.0, 74.4, 72.7, 40.3, 26.2,
18.3, ꢀ3.7, ꢀ4.6 ppm; FT-IR (neat): v˜ =2953, 2929, 2857, 1648,
1472, 1388, 1251, 1164, 1053, 1006, 964 cmꢀ1; MS (MALDI-TOF,
DCTB): m/z: 2680 [M+H]+; elemental analysis calcd. (%) for
C144H252N12O12Si12: C 64.52, H 9.48, N 6.27; found: C 63.03, H 9.43, N
6.13.
[13] a) S. I. Swamy, J. Bacsa, J. T. A. Jones, K. C. Stylianou, A. Steiner, L. K.
Ritchie, T. Hasell, J. A. Gould, A. Laybourn, Y. Z. Khimyak, D. J. Adams,
M. J. Rosseinsky, A. I. Cooper, J. Am. Chem. Soc. 2010, 132, 12773–
12775; b) Y. Jin, B. A. Voss, R. McCaffrey, C. T. Baggett, R. D. Noble, W.
Zhang, Chem. Sci. 2012, 3, 874; c) M. Kitchin, K. Konstas, C. J. Sumby,
M. L. Czyz, P. Valente, M. R. Hill, A. Polyzos, C. J. Doonan, Chem.
Commun. 2015, 51, 14231–14234.
[14] M. Liu, M. A. Little, K. E. Jelfs, J. T. A. Jones, M. Schmidtmann, S. Y.
Chong, T. Hasell, A. I. Cooper, J. Am. Chem. Soc. 2014, 136, 7583–7586.
[15] M. W. Schneider, I. M. Oppel, A. Griffin, M. Mastalerz, Angew. Chem.
2013, 52, 3611–3615.
[16] a) F. Grepioni, D. Savoia, J. Org. Chem. 1997, 62, 4180–4182; b) F. Gre-
pioni, S. Grilli, G. Martelli, D. Savoia, J. Org. Chem. 1999, 64, 3679–3683;
c) Y. N. Belokon, J. Fuentes, M. North, J. W. Steed, Tetrahedron 2004, 60,
3191–3204.
[17] a) G. Alvaro, S. Grilli, G. Martelli, D. Savoia, Eur. J. Org. Chem. 1999, 7,
1523–1526; b) S. Grilli, G. Martelli, D. Savoia, C. Zazzetta, Adv. Synth.
Catal. 2002, 344, 1068–1072; c) D. Savoia, D. Balestri, S. Grilli, M.
Monari, Eur. J. Org. Chem. 2014, 9, 1907–1914.
Acknowledgements
We thank the Engineering and Physical Sciences Research
Council (EPSRC) for financial support (EP/H000925/1), Diamond
Light Source for access to beamline I19 (MT11231), and G.
Smith (University of Manchester) for MALDI-TOF MS analysis.
We thank the Advanced Light Source, supported by the Direc-
tor, Office of Science, Office of Basic Energy Sciences, of the
U.S. Department of Energy under Contract No. DE-AC02-
05CH11231, and S. J. Teat and K. J. Gagnon for their assistance.
We acknowledge computational time on ARCHER, funded by
the EPSRC (EP/L000202/1). T.H. and K.E.J. are Royal Society Uni-
versity Research Fellows.
[18] E. J. Corey, A. Venkateswarlu, J. Am. Chem. Soc. 1972, 94, 6190–6191.
[19] V. Suresh, J. J. P. Selvam, K. Rajesh, V. Shekhar, D. C. Babu, Y. Venkates-
warlu, Synthesis 2010, 2010, 1763–1765.
Keywords: cage compounds · cycloimination · gas sorption ·
microporous materials
[20] S. Hanessian, R. Margarita, A. Hall, S. Johnstone, M. Tremblay, L. Parlanti,
J. Am. Chem. Soc. 2002, 124, 13342–13343.
[1] T. Tozawa, J. T. A. Jones, S. I. Swamy, S. Jiang, D. J. Adams, S. Shake-
speare, R. Clowes, D. Bradshaw, T. Hasell, S. Y. Chong, C. Tang, S. Thomp-
son, J. Parker, A. Trewin, J. Bacsa, A. M. Slawin, A. Steiner, A. I. Cooper,
Nat. Mater. 2009, 8, 973–978.
[2] a) M. Brutschy, M. W. Schneider, M. Mastalerz, S. R. Waldvogel, Adv.
Mater. 2012, 24, 6049–6052; b) J.-H. Zhang, S.-M. Xie, L. Chen, B.-J.
Wang, P.-G. He, L.-M. Yuan, Anal. Chem. 2015, 87, 7817–7824; c) J.-K.
Sun, W.-W. Zhan, T. Akita, Q. Xu, J. Am. Chem. Soc. 2015, 137, 7063–
7066; d) T. Uemura, R. Nakanishi, S. Mochizuki, S. Kitagawa, M. Mizuno,
Angew. Chem. Int. Ed. 2016, 55, 6443–6447; Angew. Chem. 2016, 128,
6553–6557.
[3] T. Hasell, S. Y. Chong, K. E. Jelfs, D. J. Adams, A. I. Cooper, J. Am. Chem.
Soc. 2012, 134, 588–598.
[4] T. Hasell, M. Schmidtmann, C. A. Stone, M. W. Smith, A. I. Cooper, Chem.
Commun. 2012, 48, 4689–4691.
[5] Q. Song, S. Jiang, T. Hasell, M. Liu, S. Sun, A. K. Cheetham, E. Sivaniah,
A. I. Cooper, Adv. Mater. 2016, 28, 2629–2637.
[21] a) D. Xu, R. Warmuth, J. Am. Chem. Soc. 2008, 130, 7520–7521; b) K. E.
Jelfs, X. Wu, M. Schmidtmann, J. T. A. Jones, J. E. Warren, D. J. Adams,
A. I. Cooper, Angew. Chem. 2011, 50, 10653–10656; c) P. Skowronek, B.
Warzajtis, U. Rychlewska, J. Gawronski, Chem. Commun. 2013, 49, 2524–
2526.
[22] M. W. Schneider, I. M. Oppel, H. Ott, L. G. Lechner, H. J. Hauswald, R.
Stoll, M. Mastalerz, Chem. Eur. J. 2012, 18, 836–847.
[23] H. Nowell, S. A. Barnett, K. E. Christensen, S. J. Teat, D. R. Allan, J. Syn-
chrotron Radiat. 2012, 19, 435–441.
[24] a) G. M. Sheldrick, University of Gçttingen, Germany 2008; b) L. Krause,
R. Herbst-Irmer, G. M. Sheldrick, D. Stalke, J. Appl. Crystallogr. 2015, 48,
3–10.
[25] G. Sheldrick, Acta Crystallogr. Sect. D 2010, 66, 479–485.
[26] G. Sheldrick, Acta Crystallogr. Sect. A 2015, 71, 3–8.
[27] G. Sheldrick, Acta Crystallogr. Sect. A 2008, 64, 112–122.
[28] G. Sheldrick, Acta Crystallogr. Sect. C 2015, 71, 3–8.
[6] a) L. Chen, P. S. Reiss, S. Y. Chong, D. Holden, K. E. Jelfs, T. Hasell, M. A.
Little, A. Kewley, M. E. Briggs, A. Stephenson, K. M. Thomas, J. A. Arm-
strong, J. Bell, J. Busto, R. Noel, J. Liu, D. M. Strachan, P. K. Thallapally,
A. I. Cooper, Nat. Mater. 2014, 13, 954–960; b) A. Kewley, A. Stephen-
son, L. Chen, M. E. Briggs, T. Hasell, A. I. Cooper, Chem. Mater. 2015, 27,
3207–3210; c) T. Hasell, M. Miklitz, A. Stephenson, M. A. Little, S. Y.
Chong, R. Clowes, L. Chen, D. Holden, G. A. Tribello, K. E. Jelfs, A. I.
Cooper, J. Am. Chem. Soc. 2016, 138, 1653–1659.
[7] G. Zhang, O. Presly, F. White, I. M. Oppel, M. Mastalerz, Angew. Chem.
Int. Ed. 2014, 53, 1516–1520; Angew. Chem. 2014, 126, 1542–1546.
[8] K. Ono, K. Johmoto, N. Yasuda, H. Uekusa, S. Fujii, M. Kiguchi, N. Iwasa-
wa, J. Am. Chem. Soc. 2015, 137, 7015–7018.
[29] O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H. Pusch-
mann, J. Appl. Crystallogr. 2009, 42, 339–341.
[30] E. Harder, W. Damm, J. Maple, C. Wu, M. Reboul, J. Y. Xiang, L. Wang, D.
Lupyan, M. K. Dahlgren, J. L. Knight, J. W. Kaus, D. S. Cerutti, G. Krilov,
W. L. Jorgensen, R. Abel, R. A. Friesner, J. Chem. Theory Comput. 2016,
12, 281–296.
[31] J. VandeVondele, M. Krack, F. Mohamed, M. Parrinello, T. Chassaing, J.
Hutter, Comput. Phys. Commun. 2005, 167, 103–128.
[32] J. VandeVondele, J. Hutter, J. Chem. Phys. 2007, 127, 114105.
[33] S. Grimme, J. Antony, S. Ehrlich, H. Krieg, J. Chem. Phys. 2010, 132,
154104.
[9] A. Avellaneda, P. Valente, A. Burgun, J. D. Evans, A. W. Markwell-Heys, D.
Rankine, D. J. Nielsen, M. R. Hill, C. J. Sumby, C. J. Doonan, Angew. Chem.
2013, 52, 3746–3749.
Received: July 28, 2016
[10] A. G. Slater, A. I. Cooper, Science 2015, 348, DOI: 10.1126/scien-
ce.aaa8075.
Published online on && &&, 0000
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FULL PAPER
&
Microporous Materials
P. S. Reiss, M. A. Little, V. Santolini,
S. Y. Chong, T. Hasell, K. E. Jelfs,
M. E. Briggs,* A. I. Cooper*
&& – &&
Cage decorating: Imine porous organic
cages that possess a range of chemical
functionalities on the cage periphery
were prepared. The use of different
functionalized diamine precursors led to
cage compounds of different sizes and
porosities, including one cage with the
potential for further post-synthetic
modification.
Periphery-Functionalized Porous
Organic Cages
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!