Facile synthesis of oligoyne amphiphiles and their rotaxanes

Article abstract of DOI:10.1039/c4sc03154g

Carbon-rich organic compounds containing a series of conjugated triple bonds (oligoynes) are relevant synthetic targets, but an improved access to oligoynes bearing functional groups would be desirable. Here, we report the straightforward synthesis of two

Full text of DOI:10.1039/c4sc03154g

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Facile Synthesis of Oligoyne Amphiphiles and their Rotaxanes
Stephen Schrettl,1,‡ Emmanuel Contal,1,‡ Tobias N. Hoheisel,1,2 Martin Fritzsche,1
Sandor Balog,3 Ruth Szilluweit,1 Holger Frauenrath1,*
1 Ecole Polytechnique Fédérale de Lausanne (EPFL)
Institute of Materials
Laboratory of Macromolecular and Organic Materials
EPFL – STI – IMX – LMOM
MXG 037, Station 12
1015 Lausanne, Switzerland
holger.frauenrath@epfl.ch
2 ETH Zürich
Department of Materials
Vladimir-Prelog-Weg 1-5/10
8093 Zurich, Switzerland
3 Adolphe Merklé Institute
Route de l'Ancienne Papeterie, CP209
1723 Marly, Switzerland
‡ both authors contributed equally to this publication

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Abstract
Carbon-rich organic compounds containing a series of conjugated triple bonds (oligoynes) are relevant
synthetic targets, but an improved access to oligoynes bearing functional groups would be desirable. Here,
we report the straightforward synthesis of two series of oligoynes amphiphiles with glycoside or
carboxylate polar head groups, investigate their self-assembly behavior in aqueous media, and their use as
precursors for the formation of oligoynes rotaxanes with cyclodextrin hosts. To this end, we employed
mono-, di-, or triacetylenic building blocks that gave access to the corresponding zinc acetylides in situ and
allowed for the efficient elongation of the oligoyne segment in few synthetic steps via a Negishi coupling
protocol. Moreover, we show that the obtained oligoynes derivatives can be deprotected to yield the
corresponding amphiphiles. Depending on their head groups, the supramolecular self-assembly of these
amphiphiles gave rise to different types of carbon-rich colloidal aggregates in aqueous media.
Furthermore, their amphiphilicity was exploited for the preparation of novel oligoyne cyclodextrin
rotaxanes using simple host-guest chemistry in water.
1

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Introduction
Carbon-rich organic compounds containing a series of conjugated triple bonds (oligoynes) have
attracted considerable interest because they were found in a variety of natural products,1,2 are under
consideration as molecular wires,3,4 show intriguing non-linear optical properties,5,6 and have recently
been used as molecular precursors for the preparation of carbon nanomaterials at room temperature.7-9
Moreover, homologous series of oligoynes have been investigated spectroscopically in an oligomer
approach towards the properties of the elusive carbon allotrope carbyne (C≡C)∞.5,10-15 Terminal
substituents with a high steric demand have been employed as protecting groups that hinder the
metastable16,17 conjugated triple bonds from coming into close contact. In this way, derivatives of ever
increasing length have been prepared. Notable examples include the investigations by Bohlmann,18
Jones,19 Walton,20,21 Gladysz,12,22 Hirsch,10,11,23 Cox,17 and, in particular, Tykwinski5,14 who recently
introduced the supertrityl protecting group that provided sufficient steric hindrance to stabilize oligoynes
with up to 22 conjugated C≡C bonds. Since the oligoynes in these examples did not carry any labile
functional groups, harsh reagents and conditions were typically employed in their preparation, such as
the Fritsch-Buttenberg-Wiechell rearrangement.24-28 In order to gain access to oligoynes bearing
functional groups, significantly milder reaction conditions are required, and synthetic approaches have
traditionally been based on transition-metal-catalyzed couplings such as the Cadiot-Chodkiewicz11,29-34
and Sonogashira35-41 reaction. The direct bond formation between sp-hybridized carbon atoms by these
methods has been successfully applied in the synthesis of diynes.1 The preparation of unsymmetric higher
oligoynes, however, is typically plagued by low conversions, selectivity issues, and side product formation,
as alkynes and haloalkynes are prone to undergo oxidative, and reductive homocoupling reactions under
these conditions. The Negishi reaction42-44 offers a viable alternative but has rarely been applied in the
direct cross-coupling of sp-hybridized carbons.45,46 We recently reported a heterocoupling protocol based
on the Negishi coupling that allowed us to prepare unsymmetric glycosylated oligoynes.47 The required
zinc acetylide was prepared in situ from a stable trimethylsilyl derivative and coupled with a
bromoacetylene to yield the desired heterocoupling products up to the tetrayne in high yields. When
further extending our approach to oligoynes beyond the tetrayne, however, we experienced issues of
product stability that we now found to be associated to the use of a single methylene group as a spacer
and the lability of the chosen trimethylsilyl protecting group at the oligoyne terminus.
2

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Figure 1. a) Oligoyne derivatives TAG2–6 and TPC2–6 with glycoside and carboxylate functional groups can be deprotected to
obtain b) the corresponding amphiphilic oligoyne derivatives GLU6-TIPS and MEC6-TIPS. These may either be used to prepare
carbon-rich colloidal aggregates or c) oligoyne cyclodextrin rotaxanes GLU6GLU ∙ 2 CD.
Here, we demonstrate the straightforward synthesis of two series of oligoynes TAG2–6 and TPC2–6
(Figure 1) bearing glycoside and carboxylate groups that we were able to successfully prepare up to the
hexayne derivatives on the multi-gram scale. To this end, we synthesized derivatives with an extended
spacer length between the oligoynes and the functional group, and used a sterically more demanding TIPS
protecting group at the oligoyne terminus. Moreover, we employed mono-, di-, or triacetylenic building
blocks that could be conveniently prepared on a large scale, gave access to the corresponding zinc
acetylides in situ, were compatible with the Negishi protocol, and thus allowed for the efficient and
concise elongation of the oligoyne segment in few synthetic steps. We found that the obtained oligoyne
derivatives could be deprotected to yield the corresponding amphiphiles, such as the hexayne glucoside
GLU6-TIPS or the methyl carboxylate MEC6-TIPS (Figure 1). These amphiphiles gave rise to carbon-rich
colloidal aggregates by supramolecular self-assembly in aqueous media. Finally, we exploited their
amphiphilicity for the preparation of the novel hexayne cyclodextrin rotaxane GLU6GLU ∙ 2 CD (Figure 1)
using simple host-guest chemistry in water. Hence, we have developed the tools to access and handle
amphiphilic oligoynes derivatives with labile functional groups despite their inherent chemical reactivity,
which may in turn be utilized for the further preparation of carbon-rich compounds or nanomaterials.
3

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Results and Discussion
Synthesis of Oligoyne Derivatives with Functional Groups
The synthetic approach we have applied here for the preparation of oligoynes bearing labile functional
groups extends upon the facile coupling of bromoacetylenes with zinc acetylides similar to the Negishi
coupling conditions developed previously in our laboratory.47 During scale-up of our previously reported
approach, we noticed a significantly decreased yield for large (>10 g) batch sizes and oligoynes longer
than tetraynes. For the present investigation, we therefore reduced the electronic effects of the
substituents on the oligoyne moiety by increasing the spacer length, and used the sterically more
demanding triisopropylsilyl (TIPS) group for the preparation of longer oligoynes. Moreover, we decided to
utilize the silyl-protected oligoyne zinc acetylides R-(C≡C)m-ZnCl 1–3 (R = TIPS, TMS; m = 1–3) as building
blocks in order to reduce the number of synthetic steps. To this end, the silylated precursors TIPS-C≡C-H
and TIPS-(C≡C)2-H were deprotonated with n-BuLi followed by the addition of ZnCl2 in THF to furnish
TIPS-C≡C-ZnCl
1
and TIPS-(C≡C)2-ZnCl 2a. Similarly, the precursors TIPS-(C≡C)2-TMS,48
TMS-(C≡C)2-TMS,49,50 and TIPS-(C≡C)3-TMS48 were monolithiated by the selective removal of one TMS
group using MeLi ⋅ LiBr,51 and transmetalation with ZnCl2 gave TIPS-(C≡C)2-ZnCl 2a, TMS-(C≡C)2-ZnCl 2b,
as well as TIPS-(C≡C)3-ZnCl 3, respectively. The resulting solutions of the zinc acetylides were then added
to solutions containing the palladium catalyst and the bromoacetylenes.39,40,52 In this way, we were able to
synthesize the series of diynes to tetraynes carrying the protected tetra-O-acetyl β-D-glucosides TAG2–4
(Scheme 1), in only two steps from commercial precursors, and in isolated yields for the final coupling
step of 87%, 78%, and 51% on a 1 g scale. In the same way, the corresponding tritylphenyl carboxylates
TPC2–4 (Scheme 2) were obtained in isolated yields of 68% (1 g scale), 51% (9 g scale), and 65% (1 g
scale), respectively. The key to access the higher homologues was the efficient conversion of the
bromoalkynes 5 or 9 to the corresponding TMS-protected triynes 6 and 10 (77% and 71% on a 10 g scale,
respectively) by Negishi coupling reactions with TMS-(C≡C)2-ZnCl 2b, and their subsequent desilylative
bromination39,40 to the desired bromotriynes 7 and 11, respectively. As both bromotriynes were found to
rapidly degrade in the solid state,53 we prepared 7 directly before applying it to subsequent coupling
steps, and 11 was even only generated in situ. The final Negishi coupling reactions with either the diyne
2a or the triyne 3 then furnished the tetra-O-acetyl β-D-glucosyl pentaynes and hexaynes TAG5–6 (42%
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and 55% on reaction scales of 1 g and 0.5 g, respectively) as well as the corresponding tritylphenyl
carboxylates TPC5–6 (59% and 44% over two steps on reaction scales of 0.3 g and 2 g, respectively). We
furthermore increased the batch size for the preparation of TAG6 to 6.5 g to test the scalability of the
employed procedure and obtained the desired hexayne in 43% yield.
AcO
AcO
AcO
AcO
O
O
b), c), or d)
O
O
R
TIPS
n
AcO
OAc
AcO
OAc
4
5
R = H
R = Br
TAG2 n = 2
TAG3 n = 3
TAG4 n = 4
a)
e)
AcO
AcO
AcO
AcO
O
O
g), h)
O
O
R
3
TIPS
n
AcO
OAc
AcO
OAc
R = TMS
R = Br
TAG5 n = 5
TAG6 n = 6
6
7
f)
Scheme 1. Synthesis of glycosylated oligoynes TAG2–6 up to the hexaynes. Reagents and conditions: a) AgNO3, NBS, MeCN,
93%; b) TIPS-C≡C-ZnCl 1, PdCl2(dppf) ⋅ DCM, THF/toluene, 87%; c) TIPS-(C≡C)2-ZnCl 2a, PdCl2(dppf) ⋅ DCM, THF/toluene, 78%;
d) TIPS-(C≡C)3-ZnCl 3, PdCl2(dppf) ⋅ DCM, THF/toluene, 51%; e) TMS-(C≡C)2-ZnCl 2b, PdCl2(dppf) ∙ DCM, THF/toluene, 72%; f)
AgF, NBS, MeCN, 81%; g) TIPS-(C≡C)2-ZnCl 2a, PdCl2(dppf) ∙ DCM, THF/toluene, 42%; h) TIPS-(C≡C)3-ZnCl 3, PdCl2(dppf) ∙ DCM,
THF/toluene, 55%.
O
O
b), c), or d)
O
R
O
TIPS
n
8
9
R = H
R = Br
TPC2 n = 2
TPC3 n = 3
TPC4 n = 4
a)
e)
O
O
g), h)
O
TIPS
O
R
n
3
10 R = TMS
11 R = Br
TPC5 n = 5
TPC6 n = 6
f)
Scheme 2. Synthesis of oligoyne tritylphenyl carboxylates TPC2–6 up to the hexaynes. Reagents and conditions: a) AgNO3, NBS,
DCM/MeCN, 96%; b) TIPS-C≡C-ZnCl 1, PdCl2(dppf) ⋅ DCM, THF/toluene, 68%; c) TIPS-(C≡C)2-ZnCl 2a, PdCl2(dppf) ⋅ DCM,
THF/toluene, 51%; d) TIPS-(C≡C)3-ZnCl 3, PdCl2(dppf) ⋅ DCM, THF/toluene, 65%; e) TMS-(C≡C)2-ZnCl 2b, PdCl2(dppf) ∙ DCM,
THF/toluene, 71%; f) AgF, NBS, DCM; g) TIPS-(C≡C)2-ZnCl 2a, PdCl2(dppf) ∙ DCM, THF/toluene, 59% over two steps starting from
10; h) TIPS-(C≡C)3-ZnCl 3, PdCl2(dppf) ∙ DCM, THF/toluene, 44% over two steps starting from 10.
5

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The developed synthetic pathway has, hence, allowed for the facile synthesis of unsymmetric oligoynes
up to the hexaynes with different functional groups on the preparative scale. The new acetylenic building
blocks significantly facilitated the procedure, and the obtained products were found to be considerably
more stable than the previously reported oligoynes with a methylene spacer and a TMS protecting
group.47 No decomposition was observed in the neat state, except for the hexayne TAG6 that slowly
degraded at 4 °C in the bulk over a period of six weeks and was, therefore, stored in a dilute Et2O solution
at –20 °C. Due to the expected general sensitivity of higher oligoynes a storage at temperatures of –20 °C is
nonetheless generally advisable to ensure the integrity of the compounds over the long term.
Spectroscopic Properties of the Oligoyne Derivatives
The NMR, UV-Vis, Raman, and IR spectra of the tetra-O-acetyl β-D-glucosyl oligoynes TAG2–6 and the
corresponding tritylphenyl carboxylates TPC2–6 showed trends similar to what had previously been
described for series of symmetric oligoynes.5,11,13 The UV-Vis spectra for the respective members of the
two series TAG2–6 in acetonitrile and TPC2–6 in cyclohexane were almost identical (Figure 2a,b), and
plots of the highest wavelength absorptions according to Lewis and Calvin10,20 (Figure 2c,d) as well as
extrapolations of the highest wavelength absorptions according to Wegner54 gave results in excellent
agreement with previously published values. The solid state Raman spectra of TAG2–6 and TPC2–6
(Figure 3a,b) revealed bands at positions that matched reasonably well with the vibronic fine structure
observed in the optical spectra. Consistent with previously reported data,6,11 the positions of the Raman
bands shifted toward lower wavenumbers with an increasing number of triple bonds, as illustrated by the
plots of the Raman shifts versus the inverse number of triple bonds 1/n (Figure 3c,d). The solid state IR
spectra of corresponding members of the TAG2–6 and TPC2–6 series exhibited the same peak patterns
for the oligoyne vibrations in the range of 2250–2050 cm–1 (Figure 3e,f). Finally, the 13C-NMR spectra of
these series revealed resonances for the internal acetylene carbons converging to chemical shifts between
65 and 60 ppm (Figure 4). In both series, the signals of the two acetylene carbons next to the silyl end
groups appeared above 80 ppm, while the resonances of the two acetylene carbons neighboring the
propylene spacer were observed at chemical shifts of 66 and 78–82 ppm, respectively.
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Figure 2. a) UV-Vis spectra of the tetra-O-acetyl β-D-glucosyl oligoynes TAG2–6 in acetonitrile (concentrations in the range of
c = 3.03–4.21 ꢀmol/L), and b) of the corresponding tritylphenyl carboxylates TPC2–6 in cyclohexane (concentrations in the range
of c = 5.86–6.55 ꢀmol/L). c,d) Lewis-Calvin plots of the UV-Vis absorption maxima of the two series with linear regressions with
slopes of k = 12.2 103 and 12.4 103 nm2 (R2 = 0.996 and 0.991). e,f) Plots of the energy of the optical transition versus
1/(n+0.5), with the number of triple bonds n. An extrapolation of the linear regression to n = ∞ yields values of 480 nm (2.6 eV)
and 498 nm (2.5 eV), respectively, for the saturation wavelength of an infinitely long chain of conjugated triple bonds (R2 = 0.999
in both cases).
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Figure 3. IR and Raman spectra for the series of tetra-O-acetyl β-D-glucosyl oligoynes TAG2–6 and the corresponding
tritylphenyl carboxylates TPC2–6. a,b) Solid-state Raman spectra, c,d) plots of the Raman band positions versus 1/n (the lines
serve as guides to the eye), and e,f) solid-state IR spectra of TAG2–6 and TPC2–6.
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Figure 4. Acetylene region of the 13C NMR spectra of a) the glucosylated oligoynes TAG2–6 and b) the corresponding
tritylphenyl carboxylates TPC2–6. The resonances for the internal acetylene carbons converged to chemical shifts between 65–
60 ppm (black), the acetylene carbons neighboring the TIPS group appeared above 80 ppm (orange), and the acetylene carbons
next to the propylene spacer were observed at chemical shifts of 66 and 78–82 ppm (red), respectively (glucoside and
tritylphenyl peaks highlighted in blue; * = denotes residual solvent signals from either CD2Cl2 or CDCl3).
9

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Preparation of Carbon-Rich Amphiphiles and Supramolecular Self-Assembly
The obtained oligoynes serve as protected precursors of oligoyne amphiphiles that undergo
supramolecular self-assembly into carbon-rich colloidal aggregates in aqueous dispersion and can be used
for the formation of novel oligoynes rotaxanes with cyclodextrin hosts.7,8 We first investigated the
complete deprotection of the tetra-O-acetyl β-D-glucosyl hexayne TAG6, that is, the deacetylation of the
glucosyl head group by treatment with substoichiometric amounts of NaOMe in methanol according to
Zemplén,55 and the simultaneous or subsequent desilylation with cesium fluoride (Scheme 3). Solutions of
the desilylated compound Glu6-H, however, quickly turned dark brown, indicating the fast degradation of
the hexayne moieties. While this highlighted the propensity of the deprotected hexaynes to possibly
undergo carbonization after deprotection, the rapid process was difficult to control. We therefore decided
to investigate the presumably less reactive derivatives with a deprotected hydrophilic head group but an
intact terminal silyl group. To this end, the hexaynes TAG6 and TPC6 were both deprotected using
NaOMe in MeOH-containing solutions, resulting in the glucosylated amphiphile GLU6-TIPS and the
methyl carboxylate MEC6-TIPS, respectively (Scheme 3).
HO
O
a)
b)
c)
HO
O
H
6
HO
OH
AcO
AcO
GLU6-H (dec.)
O
O
TIPS
6
HO
HO
AcO
OAc
TAG6
O
O
TIPS
6
HO
OH
GLU6-TIPS
O
O
O
TIPS
MeO
TIPS
6
6
MEC6-TIPS
TPC6
Scheme 3. Synthesis of oligoyne amphiphiles. Reagents and conditions: a) CsF, NaOMe, dioxane/MeOH, r.t., 2 h; b) NaOMe,
dioxane/MeOH, r.t., 2 h; then Amberlite (H+), 30 min; c) NaOMe, DCM/MeOH, r.t., 5 h; then Amberlite (H+), 1 h. Conversions were
quantitative in all cases, but the products were kept in solution and isolated yields not determined.
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Figure 5. a) Comparison of the solid-state IR spectra of the protected hexaynes TAG6 and TPC6 with the corresponding
deprotected glucosyl hexaynes GLU6-TIPS and methyl carboxylates MEC6-TIPS. b) Solution-phase UV-Vis spectra of deprotected
glucosyl hexayne GLU6-TIPS and c) of the hexayne methyl carboxylates MEC6-TIPS in acetonitrile (black, c = 3.83 µmol/L,
c = 4.97 µmol/L, respectively), in aqueous dispersion at the same concentration (blue, c = 3.83 µmol/L, c = 4.97 µmol/L,
respectively), and upon diluting the latter with a three-fold excess of MeCN (red, c = 0.96 µmol/L, c = 1.24 µmol/L, respectively;
shown four times magnified, for the sake of comparison).
Our investigations by IR and UV-Vis spectroscopy (Figure 5), first of all, confirmed that the hexayne
segments remained intact in both cases. Moreover, UV-Vis spectroscopy proved that both molecules
underwent a reversible aggregation without premature degradation of the hexayne moiety in aqueous
media. Thus, both the glucosylated hexayne GLU6-TIPS and the methyl carboxylate MEC6-TIPS showed
the UV-Vis absorption bands characteristic for molecularly disperse solutions in MeCN, which gave way to
a broad and less intense signal with a poorly defined fine structure in aqueous dispersion (Figure 5b,c).
Diluting these dispersions with a three-fold excess of MeCN re-established the spectroscopic fine structure
of the molecularly disperse species in both cases, proving the reversibility of the process. While the
protected oligoyne derivatives TAG6 and TCP6 were completely insoluble in aqueous media, both the
glucosylated hexayne GLU6-TIPS and the methyl carboxylate MEC6-TIPS readily formed opalescent
colloidal dispersions in water, as corroborated by dynamic light scattering (DLS) experiments in
combination with cryogenic transmission electronic microscopy (cryo-TEM) imaging. From DLS, we
determined particle sizes of 59 (±2) nm (PDI 0.230) for GLU6-TIPS (Figure 6a) and depolarized dynamic
light scattering on the dispersions was practically zero, so that shape anisotropy can be excluded.
According to representative cryogenic transmission electron microscopy (cryo-TEM) images (Figure 6b),
the dispersions contained a mixture of unilamellar and multilamellar spherical vesicles with a broad
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variation of diameters in the range of 20–120 nm. These vesicles exhibited a uniform wall thickness on the
order of 4–5 nm, suggesting that the vesicle membranes were formed from bilayers of the molecules. By
contrast, dispersions of MEC6-TIPS contained significantly larger spherical particles with a diameter of
172 (±6) nm (PDI 0.177) according to DLS (Figure 6c) and depolarized DLS. Cryo-TEM images of these
dispersion revealed what looked like filled nanospheres with a broad distribution of diameters in the
range of 20–250 nm. Since the latter are up to two orders of magnitude larger than the extended
molecular length of MEC6-TIPS of about 2.6 nm, one has to conclude that these nanospheres can not be
micelles but represent compact droplets of MEC6-TIPS. This implies that the amphiphilicity of the methyl
carboxylates was not sufficient to stabilize well-defined colloidal structures.
Figure 6. a) Dynamic light scattering (DLS) size distributions by intensity of aqueous dispersions of the glucosylated hexayne
GLU6-TIPS indicated the presence of colloidal aggregates with sizes of 59 (±2) nm (PDI 0.230). b) Cryogenic transmission
electron microscopy (cryo-TEM) images of aqueous dispersions of GLU6-TIPS revealed the presence of a mixture of unilamellar
and multilamellar spherical vesicles with a broad variation of diameters. c) DLS of the methyl carboxylate MEC6-TIPS in aqueous
dispersion showed colloidal aggregates with a size of 172 (±6) nm (PDI 0.177). d) Cryo-TEM images of these dispersions showed
filled nanospheres that supposedly represent compact droplets of MEC6-TIPS.
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Rotaxane Formation with
α-Cyclodextrin in Aqueous Solution
Rotaxanes of π-conjugated oligomers and polymers had previously been investigated as potential
“insulated molecular wires”,56 and cyclodextrins have frequently been used as hosts for small linear
hydrophobic guests.57-60 The stabilization of oligoynes by encapsulation via rotaxane formation had also
been previously discussed,56,61 but only few examples are known to date.62-64 In contrast to the previously
reported examples of oligoyne rotaxanes that relied on the coordination of the copper catalyst to the
macrocyclic host, we demonstrate here that the amphiphilic nature of the deprotected oligoynes can be
exploited for the straightforward preparation of oligoyne rotaxanes by simple host-guest chemistry with
α-cyclodextrin in hydrophilic media.
AcO
AcO
RO
RO
OR
OR
O
O
O
a)
O
O
O
TMS
3
AcO
OAc
RO
OR
RO
OR
TAG6TAG R = Ac
GLU6GLU R = H
b)
6
c)
HO
OH
O
O
O
OH
HO
HO
OH
HO
OH
O
O
O
O
OH
HO
O
HO
HO
OH
HO
HO
HO
OH
OH
O
O
HO
HO
OH
OH
O
O
O
OH
HO
OH
O
HO
O
d)
O
O
O
O
O
O
H
3
O
O
OH
OH
HO
HO
OH
HO
O
HO
OH
GLU3-H
O
HO
OH
HO
OH
HO
HO
OH
O
OH
O
O
O
OH
OH
HO
HO
HO
OH
O
GLU6GLU • 2 CD
Scheme 4. Synthesis of hexayne rotaxane GLU6GLU ∙ 2 CD and hexayne GLU6GLU. Reactions and conditions: a) CsF, THF/H2O;
then Cu(OAc)2, 2,6-Lutidine, DCM, 73%; b) NaOMe, 1,4-Dioxane/MeOH (5:1), r.t., 3 h (yield not determined); c) NaOMe,
Et2O/MeOH (4:1), r.t., 2 h; then Amberlite (H+) (product not isolated); d) α-cyclodextrin (0.1 M in H2O), 45°C, 3 h; then CuBr2,
TMEDA, r.t., 2 d, 21% over two steps.
To this end, the reaction of the TMS-protected triyne 6 with NaOMe in an ether/methanol mixture (4:1)
resulted in the complete deacetylation and simultaneous desilylation, furnishing the corresponding
glucoyslated triyne amphiphile GLU3-H after neutralization with Amberlite ion exchange resin
(Scheme 4). The highly reactive amphiphile was not isolated but immediately added into an aqueous
solution containing an excess of α-cyclodextrin at 45 °C. The resulting mixture was stirred for several
hours in order to ensure the formation of the corresponding triyne pseudo-rotaxane. However, all
attempts to isolate the pseudo-rotaxane failed in our hands, possibly due to de-threading of the
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α-cyclodextrin from the triyne upon work-up. Therefore, we decided to perform an in situ oxidative
homocoupling under Glaser-Galbraith conditions with a solution of GLU3-H in the presence of
α-cyclodextrin by the addition of CuBr2 and TMEDA followed by stirring of the mixture for 48 h at room
temperature (Scheme 4).65,66 After purification by Sephadex column chromatography in water and
preparative reverse-phase HPLC in water/acetonitrile, we thus obtained the corresponding [3]rotaxane
GLU6GLU ∙ 2 CD in 21% isolated yield, which features two α-cyclodextrin hosts threaded onto one
diglucosylated hexayne guest. For comparison, we also prepared the analogous free diglucosylated
TAG6TAG by desilylation of 6 and simultaneous homocoupling with Cu(OAc)2. The latter was then
converted into the deprotected hexayne GLU6GLU by deacetylation with NaOH/MeOH (Scheme 4).
Figure 7. a,b) MALDI-TOF mass spectrum of GLU6GLU ∙ 2 CD; the lowest mass peak of m/z 2553.2 Dalton ([M+Na]+) matched
the expected monoisotopic mass of the proposed [3]rotaxane. c) The comparison of the 1H-NMR spectra (400 MHz, 297.2 K, D2O)
of the native α-cyclodextrin (top) and the [3]rotaxane GLU6GLU ∙ 2 CD (bottom) highlighted the shifts of the α-cyclodextrin
proton signals that can be attributed to the threading onto the π-conjugated guest.
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Figure 8. Structure of the [3]rotaxane GLU6GLU ∙ 2 CD and the corresponding 2D NMR spectra (all 400 MHz, 297.2 K, D2O). a)
The proposed structure features a tail-to-tail arrangement of the two threaded α-cyclodextrin hosts. The assignment of the
1
signals in the 1H and 13C-NMR spectra was established by means of b) the H,1H-COSY NMR spectrum, c) the 1H,13C-HSQC NMR
spectrum, and d) the 1H,13C-HMBC NMR spectrum. e) The 1H,1H-ROESY NMR spectrum of the [3]rotaxane GLU6GLU ∙ 2 CD
revealed through-space contacts between H3’ of the wider 2,3-rim of the α-cyclodextrin host with the protons H9, H8, and H3 of
the hexayne glycosyl host. See Supplementary Figures S1–S4 for enlarged versions and further details.
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The structure of the [3]rotaxane GLU6GLU ∙ 2 CD was unambiguously proven by mass spectrometry
and NMR spectroscopy. Thus, MALDI–TOF mass spectra exhibited a lowest mass peak with a matching
monoisotopic mass of m/z 2553.2 Dalton ([M+Na]+) and the expected peak distribution (Figure 7a,b). The
1H NMR spectra in D2O (Figure 7c) showed the peaks of the α-cyclodextrin hosts and the amphiphilic
hexayne guest with integration values (α-cyclodextrin/hexayne 2:1) consistent with the proposed
molecular structure of GLU6GLU ∙ 2 CD. The anomeric H1’ signal of native α-cyclodextrin at δ = 4.99 ppm
had been shifted downfield to δ = 5.11 ppm, which can be attributed to the threading of the α-cyclodextrin
onto the π-conjugated guest. Moreover, the number of peaks in the 13C NMR spectra of the product was
consistent with a symmetric (head-to-head or tail-to-tail) arrangement of the two threaded α-cyclodextrin
hosts. All 1H and 13C NMR signals were unambiguously assigned by means of 1H,1H correlation
spectroscopy (COSY), heteronuclear single quantum coherence (HSQC) spectroscopy, and heteronuclear
multiple-bond correlation (HMBC) spectroscopy (Figure 8a–c). Notably, the diastereotopic protons in the
CH2 groups at C6 and C6’ of both the guest and host as well as the one at C7 of the propylene spacer
showed a strong splitting not observed in the free molecules. Moreover, rotating-frame nuclear
Overhauser effect correlation spectroscopy (ROESY) measurements proved through–space contacts
between H3’ of the wider 2,3-rim of the α-cyclodextrin host with the two proton pairs H8 and H9 of the
propylene spacers and H3 of the guest’s glucosyl residue (Figure 8d). Thus, the observed through-space
contacts combined with the absence of desymmetrization in the 1D spectra allowed us to unambiguously
conclude that the isolated product exclusively comprised the isomer with a tail-to-tail arrangement of the
two threaded α-cyclodextrin hosts, while the other two possible isomers with a head-to-head or
head-to-tail arrangement of the α-cyclodextrin hosts were absent. Although the low isolated yield of the
GLU6GLU ∙ 2 CD product did not allow us to exclude the formation of the other isomers, a similarly
specific formation of only one of the three possible isomers of a [3]rotaxane had already been
demonstrated in previous examples of α-cyclodextrin host complexes with π-conjugated guests.67,68
In marked contrast to the free hexayne GLU6GLU, the corresponding [3]rotaxane GLU6GLU ∙ 2 CD was
remarkably stable and did not show any signs of decomposition in aqueous solution or in bulk over
months at room temperature, at elevated temperatures, or upon extended exposure to daylight. In order
to further elucidate this stabilizing effect of the rotaxane formation, we subjected aqueous solutions of
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GLU6GLU and GLU6GLU ∙ 2 CD to intense UV irradiation using a 250 W Ga-doped medium pressure
mercury lamp, and recorded their UV-Vis spectra after different irradiation times (Figure 9). As expected,
the solution of GLU6GLU showed a drastic color change from yellow to brown over time, and the
corresponding UV-Vis spectra confirmed its decomposition. In marked contrast, solutions of the hexayne
[3]rotaxane GLU6GLU ∙ 2 CD did not show a color change even after 24 h of UV irradiation. Moreover, the
intensity, shape, and fine structure of its UV absorption band remained unaltered. Apparently, the
α-cyclodextrin hosts served as a sheath and thus effectively prevented any photo-degradation or
polymerization of the hexayne moieties.
Figure 9. UV-Vis spectra of aqueous solutions of a) free hexayne GLU6GLU and b) the corresponding [3]rotaxane
GLU6GLU ∙ 2 CD upon UV irradiation after different irradiation times (ambient conditions, 250 W Ga-doped medium-pressure Hg
lamp, 250–600 nm). While the unprotected hexayne moiety of GLU6GLU underwent photo-degradation, GLU6GLU ∙ 2 CD was
stable under these conditions (the apparent increase in absorption is due to partial evaporation of the solvent).
Conclusions
In conclusion, we developed a concise synthetic pathway that allowed us to prepare two novel series of
unsymmetric oligoyne derivatives bearing functional groups up to the hexaynes on the multi-gram scale.
The improved molecular design and the newly introduced acetylenic building blocks that complement our
Negishi coupling protocol allowed for the efficient and concise elongation of the oligoyne segment,
significantly facilitating the synthetic access to this class of compounds. Moreover, we were able to
deprotect the obtained molecules to obtain reactive, carbon-rich amphiphiles with different polar head
groups that self-assembled to form carbon-rich colloidal aggregates in aqueous dispersion. Furthermore,
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the amphiphilicity of the glucose oligoynes was used for the preparation of a water-soluble hexayne
rotaxane with two threaded α-cyclodextrin hosts. This encapsulation in a host-guest complex was found
to fully shield and stabilize the otherwise reactive oligoyne segments against photochemical degradation
or cross-linking. The oligoyne amphiphiles described here may hence serve as carbon-rich precursors for
the low-temperature preparation of novel types of carbon nanostructures from colloidal dispersions or
self-assembled monolayers. Alternatively, their facile self-assembly into host-guest complexes in polar
media represents a novel paradigm for the stabilization of compounds with conjugated triple bonds. This
may pave the way for the preparation of shielded molecular wires based on oligoynes that may further
serve as protected oligomer models for carbyne.
Acknowledgments
Funding from the European Research Council (ERC Grant 239831) and ETH Zürich (ETH Research Grant
ETH-05 08-2) is gratefully acknowledged.
Notes and References
Electronic Supplementary Information (ESI) available: Supplementary Figures S1–S4 and
a
comprehensive account of all experimental details, including synthetic procedures, analytical data, and
NMR spectra of all novel compounds.
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