A shape-persistent alleno-acetylenic macrocycle with a modifiable periphery: Synthesis, chiroptical properties and H-bond-driven self-assembly into a homochiral columnar structure

Article abstract of DOI:10.1039/c3cc44101f

A shape-persistent alleno-acetylenic macrocycle, peripherally decorated with eight phenolic rings, has been synthesized in enantiomerically pure form. Its electronic circular dichroism spectrum features a strong chiroptical response. In the solid state, the macrocycle stacks in pillars to form channels and the stacks undergo further self-assembly into a three-dimensional porous architecture through lateral intermolecular hydrogen-bonding. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3cc44101f

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A shape-persistent alleno-acetylenic macrocycle with a
modifiable periphery: synthesis, chiroptical properties
and H-bond-driven self-assembly into a homochiral
columnar structure†
Cite this: DOI: 10.1039/c3cc44101f
Received 31st May 2013,
Accepted 3rd July 2013
DOI: 10.1039/c3cc44101f
Manolis D. Tzirakis, Nicolas Marion, W. Bernd Schweizer and François Diederich*
www.rsc.org/chemcomm
A shape-persistent alleno-acetylenic macrocycle, peripherally decorated
with eight phenolic rings, has been synthesized in enantiomerically
pure form. Its electronic circular dichroism spectrum features a
strong chiroptical response. In the solid state, the macrocycle stacks
in pillars to form channels and the stacks undergo further self-
assembly into a three-dimensional porous architecture through
lateral intermolecular hydrogen-bonding.
By virtue of the unique properties arising from their rigid, non-
collapsible backbone, shape-persistent macrocycles (SPMs) are
frequently employed in supramolecular chemistry for the modular
construction of well-defined, three-dimensional assemblies, including
extended tubular channels, receptors for guest complexation, discotic
liquid crystals and porous organic solids.1 Non-racemic chiral SPMs
Fig. 1 (a) 1,3-Diethynylallenes (DEAs) used in our previous studies4 and (b) new DEAs
used for the construction of a chiral (c) octaphenol-substituted shape-persistent alleno-
acetylenic macrocycle (SPAAM). PG = protecting group; TIPS = triisopropylsilyl.
with a rigid asymmetric backbone, such as 1,10-binaphthyl-derived Herein, we report our preliminary results of the exocyclic function-
cyclophanes2 and metallacyclophanes,3 as well as allenoacetylenic alisation of SPAAMs with the aim of building novel, chiral
macrocycles4–6 and allenophanes,5–8 hold great promise for diverse supramolecular assemblies in solution and the solid state.
applications ranging from chiral analysis and separation, to chiral
sensing and asymmetric catalysis.9
Our first approach towards the lateral functionalisation of
1,3-DEAs included the replacement of one of the methyl groups in
In the past years, we devoted ourselves to the construction of the tert-butyl moieties by a phenolic group, while maintaining two
novel, chiral shape-persistent alleno-acetylenic macrocycles (SPAAMs), methyl groups to preserve the steric shielding of the allene moiety
and showed that a D4-symmetric tetramer exhibits outstanding (2; Fig. 1). The phenolic groups are highly suited for triggering
chiroptical properties.4 Although we envisioned SPAAMs as highly self-association of the resulting macrocycles (3; Fig. 1) through
suitable molecular structures for further elaboration into chiral H-bonding,10 while they also offer substantial versatility for
supramolecular assemblies, such studies were so far precluded by synthetic post-functionalisation. Indeed, this novel macrocycle
the lack of appropriate, self-assembly-inducing functionality in the self-assembles into columnar super-structures and further into
periphery of their all-carbon framework. In essence, studies on a 3D microporous architecture via lateral H-bonding in the
SPAAMs were limited to only one example, where the repeating unit solid state, whereas in solution, it exhibits a remarkably high
in the macrocyclic frame is an optically pure 1,3-diethynylallene chiroptical response.
(1,3-DEA 1; Fig. 1) building block bearing tert-butyl moieties
The syntheses of 1,3-DEA building block 2 and macrocycle 3 are
to provide steric shielding of the rather delicate allene core.4 outlined in Schemes 1 and 2, respectively. Ynone 4 was accessed from
commercially available 4-hydroxybenzyl cyanide in 40% overall yield
via a previously reported 6-step synthetic route.11 Treatment of 4 with
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Laboratorium fur Organische Chemie, ETH Zurich, Honggerberg, HCI, 8093 Zurich,
Switzerland. E-mail: diederich@org.chem.ethz.ch; Fax: +41 44 632 1109;
Tel: +41 44 632 2992
TIPS-protected lithium acetylide in THF, followed by quenching of
the incipient alkoxide with pentafluorobenzoyl chloride, furnished
bispropargylic ester 5 in a one-pot fashion in 70% overall yield. The
allene moiety was then introduced by a Pd-catalysed SN20-type
reaction of 5 with 2-methyl-3-butyn-2-ol in toluene. 1,3-DEA 6 bears
two terminal alkyne units masked with orthogonally cleavable
† Electronic supplementary information (ESI) available: Synthesis and spectral
characterisation of new compounds. Copies of 1H NMR, 13C NMR, UV/vis and
ECD spectra. Concentration-dependent 1H NMR and ECD studies. CCDC 926014
and 926015. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c3cc44101f
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H-bonds in the solid state of (M)-2, with OꢂꢂꢂO distances of ca.
2.64 and 2.75 Å, respectively (Fig. S7, ESI†).
With the required precursors (P)- and (M)-2 in hand, the
stepwise construction of the desired tetrameric macrocycle was
undertaken. Only the synthesis of the all-(P)-configured macro-
cycle is presented here; the all-(M)-enantiomer was obtained in an
equivalent way, starting from (M)-(ꢁ)-2 (Scheme 2). Initially, the
phenolic groups in (P)-(+)-2 were selectively protected by MOMCl in
a mixture of H2O–MTBE in the presence of a phase-transfer catalyst
(Adogens 464; methyltrioctylammonium chloride).13 Alcohol (P)-(+)-8
was unstable upon solvent evaporation and storage under ambient
conditions. Therefore, (P)-(+)-8 was subjected immediately, without
isolation, to oxidative homocoupling under standard Hay conditions.
By following this protocol, homodimer (P,P)-(+)-9 was isolated in 70%
yield over two steps. Complete deprotection of the terminal alkynes in
(P,P)-(+)-9 by dry NaOH in toluene at 90 1C furnished (P,P)-(+)-10
in 70% yield. Subsequently, in the key step of this synthesis, the
D4-symmetric tetrameric macrocycle (P,P,P,P)-(ꢁ)-11 ((P)4-11) was
obtained in 65% yield via oxidative dimerisation–macrocyclisation
of (P,P)-(+)-10, using a modified Eglinton–Galbraith variant under
high-dilution conditions. Finally, the phenolic MOM ethers in (P)4-11
were cleaved under acidic conditions to afford the desired
octahydroxyl macrocycle (P)4-3 in 90% yield.
Scheme 1 Synthesis of the 1,3-DEA derivative (ꢀ)-2. Reagents and conditions:
(i) 1. ethynyltriisopropylsilane, nBuLi, THF, ꢁ78 1C to RT, 30 min; 2. 4, ꢁ78 1C, 2 h;
3. C6F5COCl, ꢁ78 1C to 20 1C, 70%; (ii) 2-methyl-3-butyn-2-ol, [Pd(PPh3)4], CuI,
iPr2NEt, toluene, 80 1C, 60%; (iii) HCl, THF–H2O 2 : 1, 2 h; (iv) nBu4NF, THF, 0 1C,
65% for 2 steps. For details of individual steps, see ESI.† THF = tetrahydrofuran,
THP = 2-tetrahydropyranyl, TIPS = triisopropylsilyl.
Single crystals of (P)4-3, suitable for X-ray diffraction, were grown
by slow evaporation of a mixture of CH2Cl2–n-heptane 1 : 1. Only one
C2-symmetric conformer was found in the crystal lattice of (P)4-3
which adopts a crown-like conformation (Fig. 2a; see also Fig. S8a,
ESI†).4b,c Besides the rigid diethynylallene skeleton and the bulky
4-isopropylphenol moieties, the crystal structure of (P)4-3 revealed a
remarkable mode of molecular packing. Macrocycles are stacked on
top of each other, resulting in one-dimensional channels running
along the b-axis, where the empty void space (5.2 ꢃ 7.1 Å) is filled by
guest n-heptane molecules (Fig. 2b; see also Fig. S8b and c, ESI†).
The phenolic –OH groups at the periphery of individual macrocycles
interact via lateral, intermolecular H-bonds with HO-groups
from neighbouring macrocycles of different stacks, with Oꢂ ꢂ ꢂO
distances in the range 2.6–2.7 Å; dichloromethane molecules
are also incorporated in cavities between neighbouring rings
Scheme 2 Synthesis of macrocycle (P)4-3. Reagents and conditions: (i) NaOH,
MOMCl, MTBE–H2O (2 : 1), Adogens 464; (ii) CuCl/TMEDA, air, acetone, RT, 2 h,
70% for 2 steps; (iii) NaOH, toluene, 90 1C, 6 h, 70%; (iv) CuCl, CuCl2, pyridine, Ar, RT,
then addition of 10 over 24 h, 65%; (v) HCl, THF, RT, 12 h, 90%. For details of individual
steps, see ESI.† MOMCl = methoxymethyl chloride, MTBE = methyl tert-butyl ether,
Adogens 464 = methyltrioctylammonium chloride, TMEDA = N,N,N0,N0-tetramethyl-
ethylenediamine, THF = tetrahydrofuran.
protecting groups to allow selective deprotection and subsequent
dimerisation in the later stages of this synthesis. The key building
block (ꢀ)-2, a phenol-substituted 1,3-DEA, was obtained by a two-
step, sequential removal of the tetrahydropyranyl (THP; - (ꢀ)-7)
and triisopropylsilyl (TIPS) protecting groups in 65% overall yield.12
Optical resolution of (ꢀ)-2 by HPLC on a chiral stationary phase
afforded the pure (P)-(+) and (M)-(ꢁ) enantiomers (Fig. S1, ESI†).
Absolute configurational assignments were obtained as reported in
the literature (see ESI†).
Fig. 2 X-ray structure of (P)4-3: (a) side view of a single macrocycle highlighting the
Interestingly, 1H NMR measurements of both (ꢀ)-7 and (ꢀ)-2 crown-like conformation of the central macrocyclic all-carbon framework (magenta); (b)
top view of a space-filling representation of channels formed by axial stacking of
in CDCl3 or 1,1,2,2-tetrachloroethane-d2 showed an unusual
concentration-dependent behaviour in solution (Fig. S2–S4, ESI†),
which points toward a H-bond-driven self-assembly process in
macrocycles. The intramolecular distance between the van der Waals surfaces of C12
and C13a is 7.1 Å, and between C5 and C6a is 5.2 Å; (c) microporous architecture
formed by lateral self-assembly of columnar stacks viewed along the b-axis; the atom-
solution. These findings were further supported by X-ray studies,
to-atom distance of C12–C13a is 10.5 Å, and C5–C6a is 8.6 Å. Solvent molecules and
which, in turn, revealed an extended network of HOꢂꢂꢂHO hydrogen atoms are omitted for clarity. Colour code: red = O, grey = C.
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channels, which further self-assemble through lateral, intermole-
cular H-bonding interactions into a 3D microporous architecture.
To the best of our knowledge, this arrangement, reinforced by
extensive C–HꢂꢂꢂO hydrogen-bonding networks, represents the first
example of a homochiral, molecular organic porous crystal. In
solution, the enantiopure macrocycles exhibit remarkably intense
Cotton effects. We anticipate that the alleno-acetylenic macrocycle
3 will serve as an excellent platform for further funtionalisation
aimed at further stabilizing the discotic-type stacking in solution.
Such architectures may pave the way to novel, homochiral
porous organic materials with large channels that can be used,
for example, to encapsulate guests and facilitate their reactions
in an enantioselective manner.
Fig. 3 ECD spectra of enantiopure monomers (2), dimers (10), and tetrameric
macrocycles (11 and 3) measured in MeCN at 25 1C.
and participate in two O–Hꢂ ꢂ ꢂCl interactions with an average
Oꢂ ꢂ ꢂCl distance of 2.8 Å (Fig. S8b, ESI†). As a result of this
extended H-bonding network, the columnar stacks self-assem-
ble further into a 3D microporous architecture (Fig. 2c; see also
Fig. S8c, ESI†)14 that gives rise to contiguous, remarkably large
solvent channels in the crystal (Fig. S9, ESI†).15 The tetrameric
macrocycle (P)4-3 also undergoes hydrogen-bond-driven self-
assembly in solution, as suggested by the characteristic downfield
This work was supported by the ERC Advanced Grant No.
246637 (‘‘OPTELOMAC’’). We thank Dr. Pablo Rivera-Fuentes
for comments on the manuscript.
Notes and references
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¨
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1
shift of the OH protons in the H NMR spectra in CDCl3 upon
raising the concentration (Fig. S5 and S6, ESI†). The structure of
these assemblies in solution is under further investigation.
¨
2 For selected examples, see: (a) A. Bahr, A. S. Droz, M. Pu¨ntener,
U. Neidlein, S. Anderson, P. Seiler and F. Diederich, Helv.
Chim. Acta, 1998, 81, 1931; (b) T. Kawase, T. Nakamura,
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3 S. J. Lee and W. Lin, Acc. Chem. Res., 2008, 41, 521.
ECD spectroscopy was finally employed to probe the chiroptical
properties of the enantiopure macrocycles 11 and 3 (Fig. 3; see also
Fig. S10–S15, ESI†). In MeCN, both macrocycles show intense
Cotton effects centred at 257 (De = ꢀ415 Mꢁ1 cmꢁ1, 11) and
254 nm (De = ꢀ375 Mꢁ1 cmꢁ1, 3). While these values remain very
large, they are reduced with respect to the tetrameric macrocycle
peripheꢁra1lly garnered by eight tert-butyl groups (253 nm, De =
ꢀ790 M cmꢁ1 in n-hexane) (Fig. S16, ESI†).4b This reduced
intensity of the Cotton effects correlates with a reduction in the
molar extinction coefficients, presumably induced by the phe-
nolic substituents, which also increase the conformational
flexibility of the macrocycle (Fig. S16–S18, ESI†).4d Despite the
reduction in Cotton effects, the Demax-values of the tetrameric
macrocycles (P)4-3 and (M)4-3 are still approximately 42 times
larger than those of the corresponding monomers (P)-2 and
(M)-2 and roughly 8 times higher than those of the dimers
(P,P)-10 and (M,M)-10. Similar conclusions can be drawn for the
corresponding macrocycles (P)4-11 and (M)4-11 (Fig. 3; see also
Fig. S10–S13, ESI†). Also, consistent with our previous studies,
both tetrameric macrocycles display a Cotton effect centred
between 305 and 311 nm, which splits into three maxima due to
vibronic coupling.4b,c Chiral amplification as a result of self-
assembly was not observed in solution in either a polar solvent
(i.e. MeCN) or a more appropriate, apolar solvent such as
1,1,2,2-tetrachloroethane in the concentration range between
1 ꢃ 10ꢁ4 and 1 ꢃ 10ꢁ5 M (Fig. S19, ESI†).
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In summary, the bisphenol-substituted DEA derivatives (P)- and
(M)-2 have been prepared in enantiomerically pure form and further
reacted to afford the tetrameric macrocycles (P)4- and (M)4-3 bearing
eight lateral phenolic groups around the central alleno-acetylenic
all-carbon core, all available for H-bonding interactions. Thus,
consistent with our initial objectives, X-ray crystallography
revealed that (P)4-3 stacks in pillars in the solid state to form
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Chem. Commun.