Dynamic chirality, chirality transfer and aggregation behaviour of dithienylethene switches

Article abstract of DOI:10.1016/j.tet.2008.05.129

The synthesis and characterisation of a series of chiral and achiral low molecular weight organogelators (LMWGs) based on bis-amide substituted dithienylethene photochromic switches is reported. The LMWGs gelate a range of solvents depending on the specific functionalisation of the hydrogen bonding amide groups. In mixtures of chiral and achiral LMWGs the stereochemical outcome of the chiral aggregation is determined by the chiral LMWG molecules in most cases. However, for the first time we demonstrate that the stereochemical outcome of the aggregation can be influenced by the achiral LWMG molecules in some cases. Furthermore specific π-π (and/or van der Waals) interactions of chiral LMWGs 1-3o with the solvent allow the solvent to influence the control of chirality of aggregation. This influence of the solvent has a dramatic effect on whether four- or two-gel states are available.

Full text of DOI:10.1016/j.tet.2008.05.129

Tetrahedron 64 (2008) 8324–8335
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Dynamic chirality, chirality transfer and aggregation behaviour
of dithienylethene switches
Jaap J.D. de Jong a, Patrick van Rijn a, Theodora D. Tiemersma-Wegeman a, Linda N. Lucas a,
,
Wesley R. Browne a, Richard M. Kellogg b, Kingo Uchida c, Jan H. van Esch a, Ben L. Feringa a
*
a Stratingh Institute for Chemistry and Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
b Syncom, Kadijk 3, 9747 AT Groningen, The Netherlands
c Ryukoku University, Faculty of Science and Technology, Department of Chemistry of Materials, CREST JST, Shiga 5202194, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis and characterisation of a series of chiral and achiral low molecular weight organogelators
(LMWGs) based on bis-amide substituted dithienylethene photochromic switches is reported. The
LMWGs gelate a range of solvents depending on the specific functionalisation of the hydrogen bonding
amide groups. In mixtures of chiral and achiral LMWGs the stereochemical outcome of the chiral ag-
gregation is determined by the chiral LMWG molecules in most cases. However, for the first time we
demonstrate that the stereochemical outcome of the aggregation can be influenced by the achiral LWMG
Received 7 March 2008
Received in revised form 17 May 2008
Accepted 30 May 2008
Available online 5 June 2008
Keywords:
molecules in some cases. Furthermore specific p–p (and/or van der Waals) interactions of chiral LMWGs
Supramolecular
Photochromic switching
Diarylethene
1–3o with the solvent allow the solvent to influence the control of chirality of aggregation. This influence
of the solvent has a dramatic effect on whether four- or two-gel states are available.
Ó 2008 Published by Elsevier Ltd.
Amide gel
1. Introduction
our continuing program of research on smart responsive materials
based on functional LMWGs, recently, we reported a series of per-
The dynamic self-assembly of molecules into supramolecular
systems, a phenomenon that is the basis of life itself, has at once
inspired us to develop even more complex architectures and at the
same time perplexed us in our efforts to understand the funda-
mental driving forces guiding these processes.1 The control of the
organisational processes involved in self-assembly by chemical or
physical means represents a major scientific challenge and is key to
the development of supramolecular devices of nanoscale di-
mensions. Smart molecular materials, based on small molecules
into which responsive units are integrated, hold considerable
promise in achieving molecular level control over micro- and in-
deed macroscopic structure. Central to the application of responsive
molecular systems to smart supramolecular materials are proper-
ties such as rapid response and fatigue resistance. Photochromic
molecular components2 that react, reversibly, upon irradiation with
different wavelengths of light, offer considerable opportunities to
control the self-assembly of individual molecules into supramo-
lecular structures. Low molecular weight organic gelators
(LMWGs),3 containing responsive perhydrodithienylcyclopentene
photochromic switches (Fig. 1), offer such functionality.4 As part of
hydrodithienylcyclopentene photochromic switches (e.g., Fig. 1),
which incorporate hydrogen bonding (chiral) amide units to drive
supramolecular assembly.5 The primary focus of our earlier studies
rested on the interrelationship between molecular and supramo-
lecular chirality and how photochemically induced changes in the
behaviour of the (LMWG) gelators can drive complex changes in
supramolecular gel structures (Fig. 2).
Introducing chiral units into the structure of the gel forming
monomers offers an additional point of control and can allow for
new properties to be accessed.6 Previously we have demonstrated
transfer of chirality, using the sergeant soldier principal,5a where
a chiral ‘sergeant’ molecule guides a racemic compound to form
a chiral supramolecular co-assembled structure exhibiting dynamic
chirality, e.g., an LMWG gel fibre.5a The supramolecular chirality of
the assembly itself was found to be essential in transferring the
chirality of the chiral sergeant molecules to the achiral soldiers.
This prompted us to explore chirality transfer via supramolec-
ular assemblies in different environments, i.e., by varying the sol-
dier molecules and solvents employed, to further our
understanding of the effect of chiral selection during induction of
aggregation. The solvent’s ability to direct chiral assembly was
found to be critically dependent on the substitution pattern of the
sergeant and soldier molecules and as a result aggregation can
result in a four state5c (Fig. 2) or two state aggregated system
* Corresponding author. Tel.: þ31 50 363 4235; fax: þ31 50 363 4279.
E-mail address: b.l.feringa@rug.nl (B.L. Feringa).
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.05.129

J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
8325
Figure 1. Structure of a chiral dithienylethene photochromic switch in the open 1o and closed 1c state.
depending on the combinations employed. These studies demon-
strated the delicate balance involved in, and the opportunities
available to alter and control, (chiral) aggregation.
using N-methylmorpholine and 2-chloro-4,6-dimethoxytriazine
(Fig. 3). Compounds 1–15 differ in the substituent on the amide
nitrogen (Fig. 3) ranging from linear alkyl chains to cyclic alkanes
and aromatic amines. All compounds were characterised by HRMS,
1H and 13C NMR spectroscopies and exhibit the expected photo-
chemical conversion from the open state to the closed state upon
irradiation with UV (312 nm) light, which is reversed by visible ir-
radiation (>400 nm, Fig.1). In methanol solution at lexc 312 nm, the
photostationary state (PSS) reached is >95% in favour of the closed
state with the exception of 1 (77%) and 6 (87%) (for 8, 14 and 15 the
PSS in methanol could not be determined). Clear isosbestic points
were maintained over three switching cycles. This indicates that
amide derived perhydrodithienylcyclopentene switches show good
switching behaviour in methanol solution.10 For 11, 13 and 14,
which bear aromatic groups attached directly to the amide nitrogen
atom, a w10 and 20 nm bathochromic shift in the lmax of the lowest
absorption bands of the open and closed form, respectively, are
observed compared with the alkyl substituted amide switches
(1–10, 12 and 15), Table 1.
In the present contribution we report the synthesis and charac-
terisation of a series of perhydrodithienylcyclopentene photochro-
mic switches bearing (chiral) amide side groups (Fig. 3). In these
systems the gelation of organic solvents, from aprotic apolar to protic
polar, is effected through intermolecular hydrogen bonding in-
teractions between the amide units, but is influenced heavily by both
steric and electronic properties of the amide substituents. We find
that a soldier bearing non-innocent phenyl derived side groups could
influence the direction of chiral induction, presumably through p–p
interactions. Furthermore, it appears that van der Waals interactions
can direct chiral aggregation of the soldiers through specific in-
teractions with the chiral side-groups of the sergeant.
2. Results and discussion
Compounds 1–157 were obtained, in good yields, by coupling8 of
dithienylcyclopentene diacid A,9 with the corresponding amine
Compound 8 is insufficiently soluble in methanol to obtain an
UV/vis spectrum. For 14 and 15 accurate determination of the PSS
by 1H NMR spectroscopy was precluded by low solubility. Molar
Δ
absorptivities in parentheses (
3
¼ꢀ104).
Δ
Gel (α) 1o
Gel (β) 1o
Vis
Gel (β) 1c PSS
Sol 1o
*
cooling
Δ
heating
*
UV
Vis
UV
*
Δ
2.1. Gelation behaviour
Sol 1c PSS
Gel (α) 1c PSS
Δ
The aggregation (gelation) behaviour3 of 1–15 was examined in
a series of solvents (Table 2). It is apparent that the amide func-
tionalized dithienylethene switches in the open state are capable of
gelating both apolar and aprotic solvents with gelation occurring
spontaneously upon cooling.11 The driving force for gelation is
expected to be due primarily to the hydrogen bonding interactions
between the amide functional groups. Indeed it is clear that steric
hindrance in proximity to the hydrogen bonding component (i.e.,
Figure 2. The four-gel-state cycle. The stable gel states formed by cooling solutions of
the open form (1o) (gel state ) or at the PSS365 nm (gel state ) are distinct. Once in the
gel state the structure is effectively ‘locked’ so that a stable gel formed by cooling 1o
results in formation of gel ( ) 1o, which can then be irradiated to the meta-stable gel
state ( ) 1c. Upon heating to dissolution and subsequent cooling to regelate the so-
lution the stable gel ( ) 1c is formed, which can then be irradiated with UV light to
meta-stable gel ( ) 1o and finally converted via a heating-cooling cycle to the original
gel state (
). PSS¼photostationary state, the suffixes ‘o’ and ‘c’ denote the open and
closed forms of the photochromic switches. and refer to two distinct gel states.
a
b
a
a
b
b
a
a
b
Figure 3. The switchable amide based gelators 1–15 were prepared from methylthiophene.9 (i) 2 equiv 2-chloro-4,6-dimethoxytriazine, 4 equiv N-methylmorpholine, 2 equiv of
the appropriate amine, DCM, 0 ꢁC. See Section 4 for details.

8326
J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
Table 1
13o shows a benefit of reducing such interactions in terms of
gelation.
The flexibility of the side group has a considerable effect on
gelation behaviour. The cyclohexyl substituted LMWGs, 2o
(–CH(CH3)C6H11), 9o (–C6H11) and 10o (–CH2C6H11), demonstrate
the importance of steric interactions in achieving gelation. Com-
pounds 2o and 9o, both of which are substituted at the amide ni-
trogen with secondary carbon centres, are capable of gelating
a broad range of solvents, whilst for 10o gelation behaviour similar
to that of 5o (C3H7) is observed.
Similar trends with regard to the effect of steric crowding
around the amide nitrogen atom can be seen in the alkyl phenyl
derivatised LMWGs. Whereas for the alkyl phenyl bearing gelators
1o, 3o and 15o, in which the amide nitrogen is substituted with
a secondary carbon centre, very good gelation characteristics are
observed (Table 1), a reduction in steric crowding at the C1 position
(i.e., 12o (–CH2C6H5)) results in a near complete loss in gelation
strength. For 4o, bearing a tert-butyl group, gelation is inhibited,
resulting in either precipitation or improved solubility at room
temperature, indicating that over-crowding at the C1 position in-
creases intermolecular separation and reduces potential hydrogen
bonding interactions.
Overall, it is apparent that the ability of the compounds shown
in Figure 3 to engage in gelation is critically dependent on the
nature of the C1 atom of the alkyl amide substituent. Indeed the
introduction of a methyl group at this position, e.g., 1–3o and 15o,
introduces sufficient rigidity for hydrogen bonding between the
amide units to form gel fibres.
UV/vis maxima for 1–15o and 1–15c in MeOH solution
PSS
Open
Isosbestic points
(nm)
Closed
lmax (nm)
l
lmax (nm)
1
2
3
4
5
6
7
9
10
11
12
13
14
15
0.77
0.95
0.95
0.96
0.99
0.87
0.99
0.99
0.99
0.99
0.95
0.99
n.d.
262 (2.8)
262 (2.0)
262 (2.9)
261 (2.5)
261 (2.7)
260 (2.4)
261 (2.5)
260 (2.7)
262 (2.1)
280 (3.1)
262 (2.8)
284 (2.8)
283 (2.0)
268 (3.6)
315
311
312
285
311
310
310
312
312
233, 241, 329
313
235, 248, 332
224, 331
314
350 (0.51), 520 (0.57)
349 (0.44), 510 (0.54)
348 (0.69), 520 (0.76)
348 (0.63), 520 (0.70)
348 (0.74), 514 (0.79)
347 (0.56), 517 (0.59)
348 (0.67), 518 (0.71)
345 (0.67), 511 (0.74)
347 (0.54), 520 (0.59)
312 (1.3), 350 (1.1), 541 (1.1)
350 (0.65), 520 (0.68)
316 (1.2), 353 (1.2), 539 (1.1)
357, 540
n.d.
350, 514
the amide group) has a considerable influence on the gelation be-
haviour observed. Overall, reducing steric hindrance at the -po-
sition facilitates gelation (1o–3o, 9o, 11o, 13o–15o). This holds for
further reduction in the steric hindrance also (5o–9o, 12o), albeit
with higher minimum gelation concentrations and a reduction in
solvent scope.
Solvents are ordered according to dielectric constant.
P¼precipitate, S¼solution, C¼crystallisation, VS¼viscous solution,
G¼gel. Number in bracket indicates minimal gelation concentration
in milligrams per millilitre.
a
In our earlier studies we demonstrated that molecular chirality
can be extended to control chirality in supramolecular systems and
vice versa.5 In the following sections we will examine chiral ag-
gregation phenomena in these remarkable LMWG based systems to
attempt to understand how the stereochemical properties of the
gel fibres, and hence the gel formed, is controlled by the stereo-
chemistry at the amide-C1 position and what importance can we
place on secondary interactions between the side chains in dic-
tating the stereochemical outcome.
2.2. Effect of steric crowding on gelation by LMWGs
For the linear alkyl substituted LMWGs, 5–8o, an increase in
chain length results in a change in behaviour from gelation/pre-
cipitation for 5o (C3H7), to gelation for 6o (C6H13), to mostly viscous
solutions for 7o (C12H25) and 8o (C18H37) indicating that, overall,
gelation is disrupted by an increase in the contribution of van der
Waals interactions between the alkyl chains. This is in agreement
with recent findings for gelators derived from cyclohexane bis-
ureas and bis-amides,12 where the increase in chain length en-
hances the gelation properties, only where it facilitates anisotropic
fibre growth.
Substitution at the amide position by an aromatic group (11o,
13o and 14o) provides for good gelation characteristics; however,
direct comparison with the alkyl based gelators should be made
with caution as the electronic effect (vide supra) of the aromatic
substituent on the amide group and its affect on hydrogen bond
strengths cannot be ignored. The contribution of secondary in-
2.3. Soldier effect of 5–12o on the chiral aggregation of 1–3o
In our earlier reports we demonstrated that the chirality of the
amide component of the LMWGs could be transferred to the pho-
tochromic component via the supramolecular structure of the gel
fibres.5a In the present study, the transfer of the chirality of the
amide component to the photochromic components of achiral
LMWGS co-assembled within the same gel fibres, the effect of
solvent on the transfer and the interaction between chiral and
achiral molecular units of the gel fibres is examined.
teractions, in particular p–p stacking, are unlikely to be significant
considering the negligible effect that tert-butyl substitution on
the phenyl ring has on gelation. Indeed comparison of 11o and
LMWGs (chiral) 1o–3o were co-assembled with achiral LMWGs
5o–12o. The chirality is expected to be controlled by the chiral
Table 2
Gelation characteristics for dithienyl cyclopentenes 1o–15o
Solvent
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Hexadecane
Cyclohexane
Phenyloctane
Toluene
Decalin
Dibutylether
Benzene
P
G (1)
G (1)
G (1)
G (1)
G (1)
G (5)
G (3)
G (3)
G (8)
G (8)
P
G (1)
G (1)
G (1)
G (3)
G (1)
G (1)
G (10)
S
S
P
P
S
P
P
P
P
P
P
S
S
S
S
S
S
S
P
P
C
G (10)
VS
VS
VS (10)
VS (10)
VS
VS
VS (10)
P
P
S
S
S
VS (10)
S
VS (10)
VS (32)
VS (22)
VS (12)
VS (10)
s
P
P
P
S
P
G (5)
G (2)
G (5)
G (3)
G (2)
G (2)
G (10)
G (5)
P
P
C
S
S
P
P
P
P
P
P
P
P
P
P
G (2)
G (2)
G (1)
G (3)
G (2)
G (2)
G (10)
G (2)
P
G (2)
G (2)
G (1)
P
G (2)
P
G (10)
G (3)
P
P
P
P
P
G (4)
G (2)
G (1)
G (5)
G (2)
G (2)
G (10)
G (2)
S
G (4)
G (2)
G (1)
G (1)
G (2)
G (2)
G (4)
S
S
S
S
S
G (2)
G (5)
G (4)
G (2)
G (10)
G (10)
G (4)
S
G (2)
G (1)
S
G (1)
G (1)
G (3)
P
G (3)
G (3)
G (1)
G (3)
G (3)
G (3)
S
S
S
S
S
G (2)
P
P
S
C
C
P
S
C
G (10)
Tetralin
S
S
S
S
S
S
G (2)
1,4-Dioxane
Butylacetate
1,2-DCE
2-Octanol
Ethanol
S
S
S
S
S
VS (10)
S
S
VS (10)
S
S
G (10)
S
P
P
S
S
S
S
S

J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
8327
Table 3
Sign of CD signal (
and 9o–12o (1:1) in toluene
‘sergeant’ molecules (i.e., 1o–3o), which guide the assembly of the
achiral ‘soldier’ molecules (i.e., 4–15). The combination of sergeant
LMWGs (1o–3o, 1 mg/ml) and soldier LMWGs (5o–7o, 9o–12o) to
form gels in a 1:1 ratio in toluene was examined and the chirality of
the supramolecular assembly formed was determined by CD
spectroscopy (Fig. 4 and Table 3).
It appears that after co-gelation of 1o with the series of achiral
gelators, 5o–7o and 9o–12o, in toluene, the CD signal observed
indicates that the helicity of the gel fibres is the same as observed
for gels of 1o alone (i.e., negative). This indicates that 1o is directing
the chirality of the aggregates by chiral induction during co-ag-
gregation occurring in the same manner in each case.
For 2o a different situation is observed. Gel formation with 2o
shows positive helicity, however, the sign of the CD signal of the co-
assemblies varies considerably with 5o, 6o, 10o, 11o and 12o
showing negative helicity and 7o and 9o positive helicity. This in-
dicates that the chiral selection inverts for some of the soldier
LMWGs. In the absence of strong interactions, over and above the
hydrogen bonding amide groups of 7o and 9o, it is most probable
that specific van der Waals interactions between the side chains has
a considerable effect.
For 3o, which shows positive helicity in the gel state in toluene,
the sign of the CD absorption can be tuned upon addition of dif-
ferent (soldier) switches bearing either aromatic auxiliary groups
(11o–12o, negative helicity) or non-aromatic auxiliary groups (5o–
7o, 9o–10o, positive helicity). It appears that when the soldier
gelator is given a means to interact strongly with the sergeant, for
l
¼318 nm) for mixtures of sergeants 1o–3o and soldiers 5o–7o
5
6
7
9
10
11
12
1
2
3
ꢂ
ꢂ
þ
ꢂ
ꢂ
þ
ꢂ
þ
þ
ꢂ
þ
þ
ꢂ
ꢂ
þ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
inherently chiral (amide) dithienylethenes. Switches 1o–3o, each
incorporating different chiral amide side groups, were examined in
a series of solvents to assess whether the expression of molecular
chirality upon aggregation in the supramolecular assembly could
be influenced by solvent (Fig. 5 and Table 4).
For all solvents examined, gels formed by 1o show a negative
exciton coupling (Fig. 2a) and although the intensity of the signal
varies dramatically over the series of solvents, the maximum
(l
¼ 320 nm) is relatively invariant.13 This indicates that for 1o, the
helicity of the aggregates is solvent independent, which was con-
firmed by HPLC analysis of 1c obtained by irradiation of gels of 1o in
toluene (ꢂ94% de), benzene (ꢂ53% de), decaline (ꢂ96% de), dibu-
tylether (ꢂ93% de), and cyclohexane (ꢂ96% de). For all solvents
examined, the UV/vis absorption shows a red shift upon aggrega-
tion (gelation), however, most of the absorption spectra are ob-
scured at 300–320 nm due to the high gelator concentrations
required to form gels.
In contrast to 1o, for 2o the sign of the CD absorption changes
depending on the solvent employed (Fig. 5, centre).14 For 2o the CD
absorption inverts (negative exciton coupling) upon changing from
cyclohexane (ꢂ77% de), hexadecane (ꢂ25% de) or dibutylether
(ꢂ44% de) to (positive exciton coupling) toluene (91% de), phe-
nyloctane (85% de) or decaline (70% de). For 2o the intensity of the
signal varies considerably depending on the solvent employed, al-
though the lmax (317 nm) of the absorption is unaffected. It was
anticipated that the change in signal would correspond to an in-
version of the chirality of the diastereomer of 2c obtained upon
photochemical ring closure in the gel state. Indeed in each case the
sign of the CD signal observed correlates well with the di-
astereomer of 2c obtained, as determined by HPLC, although with
varying maximum yields of induction. A simple correlation of CD
exciton coupling sign and solvent properties, i.e., change in di-
electric constant, aromatic versus non-aromatic, etc., is not
apparent.15
example, via
p–p interactions of the phenyls, it is not the chiral
compound that is directing aggregation, but the achiral compound.
This indicates that the phenyl derivatised switches 11 and 12 are
capable of shielding the phenyl group of 3o from the solvent,
allowing it to assist in aggregation and lead to an inversion of the
chiral selection. This is remarkable since the solvent is present in
large excess compared to both 11o and 12o, but nevertheless the
achiral LMWGs are still capable, presumably by means of pre-as-
sembly with 3o, to orientate the helicity in a direction opposite to
that obtained on its own.
It is apparent that secondary interactions of the gelator side
groups are capable of tipping a delicate balance and thereby in-
fluence the helicity of the gel fibres formed. These results (Table 2)
and our earlier reports,5 open the possibility of combining changes
in solvent properties with chiral dithienylethene switches 1o–3o to
determine the specific interactions present in the aggregated state.
The diastereomers of 2c can be observed by 1H NMR spectros-
copy through the appearance of characteristic absorptions at 6.65
and 6.63 ppm (in chloroform-d1) upon irradiation of 2o with UV
light. Irradiation of gels in either cyclohexane or toluene lead to the
appearance of an intense purple colour. 1H NMR spectra in chlo-
roform-d1, of the purple solid obtained by evaporation of the
2.4. Solvent effect on chiral aggregation of 1–3
The observation that secondary interactions between different
gelator units can influence chiral self-assembly, it was anticipated
that solvent could show a similar influence on the aggregation of
Figure 4. CD spectra for mixtures of 5o–12o with (a) 1o, (b) 2o, and (c) 3o in toluene (1 mg/ml, 1:1 ratio). For (a) 1o all signals show negative sign (top to bottom 12, 5, 7, 9, 6),
whereas for (b) 2o (top to bottom 7, 2 (only), 9, 10, 6, 12) and (c) 3o (top to bottom 9, 3 (only), 10, 7, 12) the sign changes from positive to negative. Spectra for compound 1o have
been reported earlier in Ref. 5c (and Fig. 2 therein).

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J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
Table 4
(a)
50
0
Sign in the CD spectrum of the exciton coupling for 1o–3o in the gel state and ob-
served diastereomeric ratio for 1c–3c by HPLC
-50
1
2
3
Benzene
Decalin
ꢂ
ꢂ53%
ꢂ96%
ꢂ93%
nd
þ
ꢂ
þ
ꢂ
ꢂ
þ
nd
70%
þ
ꢂ
ꢂ
þ
ꢂ
ꢂ
þ
40%
-100
-150
-200
-250
-300
-350
-400
-450
ꢂ
ꢂ77%
ꢂ63%
92%
ꢂ23%
ꢂ92%
55%
Dibutylether
Phenyloctane
Hexadecane
Cyclohexane
Toluene
ꢂ
ꢂ44%
ng
ng
ꢂ
85%
ꢂ25%
ꢂ77%
91%
ꢂ96%
ꢂ96%
H
N
H
N
ꢂ
S
S
O
ng¼gelation not observed. nd¼not determined due to the high concentration re-
quired for gelation. Note that the sign of the diastereomer observed has been as-
signed arbitrarily and is not related to the observed exciton coupling.
O
1o
300
320
340
Wavelength (nm)
360
380
400
Compound 3o shows a solvent dependence of the CD spectra of
its gels (Fig. 5c). The high concentrations of 3o and hence high UV
absorption precluded observation of the entire CD exciton band of
3o gel. Nevertheless the sign of the CD signal could be determined
from the red edge of the CD signal and trends were observed. For
aromatic solvents such as toluene, benzene and phenyloctane,
a positive exciton coupling was observed, whereas for non-aro-
matic solvents such as decalin, n-dibutylether, cyclohexane and
n-butylacetate, the exciton coupling was negative. This suggests
that the phenyl side groups of 3o play an important role in de-
termining aggregation behaviour, as was observed in the behaviour
of 3o with achiral substituted dithienylethenes also (vide supra). If
the aromatic side groups are shielded by the solvent, e.g., the
120
100
80
(b)
H
N
H
N
60
S
S
O
O
2o
40
20
0
-20
-40
-60
-80
phenyl can give
p–p interactions with the aromatic solvent, the
sign of the aggregates changes from negative to positive. Probably
for 3o, in contrast to 1o, the more flexible longer C2 spacer posi-
tions the phenyl further away from the chiral groups adjacent to the
amide functionality, which allows for control of the chiral induction
300
320
340 360
Wavelength (nm)
380
400
exclusively by the chiral a-carbon in combination with the amide.
(c)
Irradiation of gels of 3o in benzene (40% de), phenyloctane (92% de)
and toluene (55% de) results in stereochemical induction with an
opposite sense to that of gels of cyclohexane (ꢂ92% de), decaline
(ꢂ77% de), hexadecane (ꢂ23% de) and dibutyether (ꢂ61% de).
Again verification of the differences in the diastereomers formed
was obtained by 1H NMR spectroscopy. Gels of 3o in either cyclo-
50
0
-50
-100
-150
-200
-250
-300
-350
hexane or toluene were irradiated with
l
¼312 nm light and the
H
N
H
solvent removed by evaporation to yield purple powders. The 1H
NMR spectra (in CDCl3) of the powders showed that a different
diastereomer (de >90%) of 3c was formed (absorption at 6.60 ppm)
N
S
S
O
O
3o
in the toluene gel than that formed in
a cyclohexane gel
(6.58 ppm).16
In summary for 1o, in all solvents examined, the sign of the CD
absorption upon aggregation is always negative, and a single di-
astereomer is formed upon irradiation with UV light. For 2o the
sign for the CD absorption appears to be sensitive to van der Waals
interactions while for 3o in aromatic solvents positive exciton
couplings are observed whereas in non-aromatic solvents an ab-
sorption with a negative exciton coupling is observed upon ag-
gregation. The influence of achiral solvent on not only the
formation of a gel state but also the supramolecular chirality of the
gel is remarkable. In the next section we discuss how this influence
could affect the four-gel-state chiral aggregation system reported
recently.5c
300
320
340
Wavelength (nm)
360
380
400
Figure 5. CD spectra for gels of (a) 1o, (b) 2o and (c) 3o in selected solvents. Although
the intensity changes dramatically for 1o depending on the solvent employed, a neg-
ative exciton coupling is observed in every case. From bottom to top: phenyloctane,
decaline, butylether, benzene and tetraline. For 2o the CD absorption inverts upon
changing from hexadecane or dibutylether (negative exciton coupling) to phenyl-
octane or decaline (positive exciton coupling). Tetraline, butylacetate, dioxane, and
benzene all give very small CD signals even though the induced de is very high (vide
infra). CD spectra for 3o (lower) in selected solvents, phenyloctane ( ), benzene ( ),
hexadecane ( ), n-dibutylether ( ) and decaline ( ).
solvent, show that for the gels prepared from toluene a single di-
astereomer (de >90%) is obtained as is evident from the absorp-
tions for 2c (thiophene proton) at 6.65 ppm and for the gels
prepared from cyclohexane at 6.63 ppm. This is in agreement with
HPLC data (vide supra) and indicates that the inversion in the sign
of the CD signal is indeed correlated to the formation of a specific
diastereomer.
2.5. Four-gel states versus two-gel states
The clear differences in the solvent dependence of the aggre-
gation of 1o–3o prompted us to investigate if the four different gel
states found for 1 in toluene could be observed for compounds 2
and 3 also in other solvents. In addition to toluene used previously
for 1, cyclohexane was an obvious choice. It has a wider electronic

J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
8329
spectral window compared to toluene, but more importantly, it is
possible to observe if the inversion of sign of CD signal for 2o and 3o
(using either toluene or cyclohexane as solvent) correlates with the
differences in helicity in 2c and 3c upon photochemical ring closure
in the aggregated states. Figure 6 shows the results obtained for 1 in
cyclohexane,17 and Figures 7 and 8 and 9 and 10 show the results of
similar experiments in both toluene and cyclohexane for 2 and 3,
respectively.
chirality is observed. Hence in contrast to 1, for 2 in toluene only
two aggregation states can be addressed. It is interesting to note
that the UV/vis absorption spectra of the closed forms are not
significantly different in the gel or solution state, especially in
comparison with the changes observed for 1.
The solubility of 2o in cyclohexane is poor compared to that in
toluene, however, CD spectra could be obtained for all four states
(Fig. 8). The CD spectra appear similar to those of 1 and the signal
for 2c in cyclohexane inverts as expected. This indicates that the
results obtained for the solvents examined indeed correlates to the
sign of the stable open form. Depending on the direction of chiral
selection either two or four chiral states can be addressed for 2. In
contrast to 2 in toluene, in cyclohexane, the UV/vis absorption
spectra show significant changes for 2c in the aggregated state.
Very similar behaviour is observed for 3 in toluene (Fig. 9) and
cyclohexane (Fig. 10) as observed for 2. This indicates that the
amide group by itself is not wholly responsible for the aggregation
phenomena observed, and that a secondary interaction is involved,
in particular in obtaining the four chiral gel states. For 1 and 3 the
As described previously for gels of 1 formed in toluene,5c in
cyclohexane (Fig. 6) the CD spectra after solvent gelation are similar
in sign to those observed in toluene. Assembly of 1o into the gel
state in cyclohexane is stereoselective, leading to CD absorptions
with a negative exciton coupling. Upon irradiation with UV light
(
l
¼312 nm) the supramolecular chirality inverts to a meta-stable
state (Fig. 6c and d, dashed line), and heating and subsequent
cooling to release and reform the 1c aggregates results in an in-
version of helicity (Fig. 6c and d, solid line). It was thus possible to
observe the inversion of chirality for cyclohexane gels containing
1c, which leads to the four-gel states as described earlier5c for this
system in toluene.
secondary interactions are most probably
p–p interactions, how-
In toluene, 2o assembles as gel fibres with P helicity (Fig. 7) as
opposed to the M helicity of gel fibres formed by 1o, despite both
compounds having chiral side groups of R configuration. Upon ir-
ever, for 2 this is not so apparent. The difference might be attributed
to van der Waals interactions between the cyclohexane group or
a steric effect, and this is currently under investigation.
radiation (
l
¼312 nm) of the gel of 2o an absorption appears at
The sequential processes shown in Figures 6, 8 and 10 complete
a full cycle of four addressable chiral aggregated states and together
comprise a four state chiroptical supramolecular switch (see Fig. 2).
Despite the fact that there is no stereoselectivity in solution, after
formation of chiral aggregates of 1o–3o the molecular chirality can
longer wavelengths, and after heating and subsequent cooling to
release and reform the gel fibres the CD absorption changes but
does not invert. Subsequent irradiation with visible light
(l > 420 nm) leads to a gel containing 2o, however, no inversion of
Figure 6. UV/vis (a/b) and CD spectra (c/d) of 1 in cyclohexane; (a/c) gel
apparent for both CD and UV/vis spectra that the electronic character of the open and closed forms with respect to in solution are affected differently by incorporation into either
the or gel states. The UV/vis spectra of (a) 1o (dotted line) and (b) 1c (dotted line) in solution are shown for comparison.
a 1odsolid line, gel b 1oddashed line. (b/d) gel a 1cddashed and gel b 1cdsolid line (4 mg/ml). It is
a
b

8330
J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
Figure 7. UV/vis (a/b) and CD spectra (c/d) for 2 in toluene (1 mg/ml). (a/c) solid line is gel
spectra for (a) 2o and (b) 2c in solution are also shown (dotted lines).
a 2o, dashed is gel b 2o. (b/d) gel a 2oddashed line and gel b
2cdsolid line.20 The UV/vis
be locked subsequently with near absolute stereocontrol in the
aggregates. In turn, the molecular chirality obtained governs both
the stability and helicity of the aggregate. Transfer of molecular
chirality to supramolecular chirality and back is thus established. Of
particular significance is that meta-stable chiral aggregates can be
obtained in a reversible manner and that the aggregation process
can be controlled by an externaldi.e., lightdsignal.
interplay of molecular and supramolecular chirality. In the present
study the presence of a photo-reponsive unit, i.e., the dithienyl-
ethene unit, in the LMWGs presents a distinct opportunity in un-
derstanding such delicate processes through the ability to switch
between stable and meta-stable states in a fully reversible light
controlled manner. The meta-stable states, which are inaccessible
via direct aggregation are especially attractive as components in
functional materials. Furthermore the control of chirality at several
hierarchical levels in a synthetic system allows for furthering of
our understanding of complex (bio-)molecular supramolecular
processes.
3. Conclusions
It is demonstrated in this study for the first time that the
stereochemical outcome of the supramolecular aggregation of
LMWG can be influenced by an achiral LMWG as well as the
nature of the solvent. Compounds 2 and 3 show different (i.e.,
solvent dependent) aggregation during chiral dynamic selection,
which reveals that the (phenyl) side group is important during
chiral selection. For 3o in aromatic solvents the phenyl side
4. Experimental section
4.1. General
Reagents and solvents were obtained from commercial sour-
ces (Aldrich, Acros Chimica, Fluka) and used without further
purification unless stated otherwise. Melting points were de-
termined using a Bu¨chi melting point apparatus and are un-
corrected. 1H NMR spectra were recorded on a Varian VXR-300
spectrometer (at 300 MHz) or a Varian 500 spectrometer (at
500 MHz) at ambient temperature. The splitting patterns are
designated as follows: s (singlet); d (doublet); dd (doublet of
doublets); t (triplet); q (quartet); m (multiplet) and br (broad
peak). 13C NMR spectra were recorded on a Varian VXR-300 (at
group is presumed to have
p–p interaction with the solvent,
leaving this auxiliary group unable to participate in the selection
upon aggregation. This leads to chiral selection exclusively by
the chirality adjacent to the amide functionality in combination
with the hydrogen bonding between amides. In non-aromatic
solvents the phenyl side groups are free to participate in chiral
selection together with the amides, leading to the four-state-gel
system. Although it is unclear at present what the additional
interaction is for 2, it shows similar solvent dependent
behaviour.
75.4 MHz). Chemical shifts are denoted in
d (ppm) referenced to
The delicate balance that exists between molecular chirality and
the stability of supramolecular aggregates in natural systems, such
as actin filaments and the process of protein folding, relies on the
the residual protic solvent peaks. Coupling constants J, are
denoted in hertz. Masses were recorded with an MS-Jeol mass
spectrometer, with ionisation according to CIþ, DEI or EIþ

J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
8331
Figure 8. UV/vis (a/b) and CD spectra (c/d) for 2 in cyclohexane (1 mg/ml). (a/c) gel
UV/vis spectra of (a) 2o and (b) 2c in solution are also shown (dotted lines).
a
2odsolid line, gel
b
2oddashed line. (b/d) gel
a
2oddashed line and gel
b
2cdsolid line. The
procedures. Aldrich, silica gel, Merck grade 9385, (230–400 mesh)
was used for column chromatography. Solvents were distilled and
dried before use, if necessary, using standard methods. For all
spectroscopic measurements Uvasol (Merck) grade solvents or
better were employed. The compounds synthesised are light
sensitive and were handled, therefore, exclusively in the dark
using brown glassware, and column chromatography was per-
formed under yellow light. Irradiations were performed with
a high pressure mercury/xenon lamp (200 W, Oriel) or a xenon
lamp (300 W, Oriel) and the appropriate highpass or bandpass
filters (Andover corporation). Additionally, UV light was obtained
from a spectroline longlife filter nominally at 312 and 365 nm.
UV/vis measurements were performed on a Hewlett–Packard HP
8453 diode array spectrophotometer. CD spectra were recorded
on a JASCO J-715 spectropolarimeter. Electrochemical data were
obtained as reported earlier.18
carried out until either a gel was no longer obtained or until the
total volume exceeded 1.0 ml.
4.3. Syntheses
4.3.1. Compound 1, 1,2-bis(20-methyl-50-{[((R)-1-phenylethyl)-
amino]carbonyl}thien-30-yl)cyclopentene
1,2-Bis[50-carboxylic-acid-20-methyl-thien-30-yl]cylopentene
(A) (0.50 g,1.44 mmol) was suspendedin CH2Cl2 (5 ml) andplaced in
an ice bath. Subsequently N-methylmorpholine (0.31 ml, 2.9 mmol)
was added and the suspension became a solution. Then 2-chloro-
4,6-dimethoxytriazine (0.50 g, 2.9 mmol) was added, and a white
precipitate was formed immediatelyafter this addition. The reaction
mixture was stirred for 2 h at 0 ꢁC, and then another 2 equiv of
N-methylmorpholine (0.31 ml, 2.9 mmol) was added followed by
(R)-phenylethylamine (0.37 ml, 2.9 mmol). Stirring was continued
for 1 h at 0 ꢁC. The reaction mixture was stirred overnight at room
temperature. CH2Cl2 (50 ml) was added and the solution was
washed with, respectively, 1 M aq HCl (2ꢀ20 ml), brine (1ꢀ20 ml),
saturated aqueous bicarbonate solution (1ꢀ20 ml) and H2O
(1ꢀ20 ml). The organic phase was dried (Na2SO4) and evaporation of
the solvent afforded a solid product. After purification by column
chromatography (silica gel, CH2Cl2/MeOH 60:1) and stirring in ex-
4.2. Determination of critical gelation concentration
The following procedure was used for all compounds and
solvents. A 2 ml vial with screw cap was charged with 1.0 mg of
compound and 0.10 ml of solvent was added. The mixture was
heated until the powder dissolved with subsequent cooling to
room temperature resulting in gelation (G), precipitation (P),
crystallisation (C) or the compound remaining dissolved (S). By
inverting the vial, ‘the inverted test tube method’,19 it could be
established if gelation was successful. Gelation is considered
successful if the solvent showed no gravitational flow during
inversion. If successful, a subsequent addition of 0.10 ml of the
appropriate solvent and repetition of the previous steps was
cessetherwithafewdrops ofMeOH, an off-whitesolid wasobtained
23
(0.28 g, 35%), mp 207 ꢁC (dec); [
a
]
D
ꢂ83.5 (c 0.99, MeOH); 1H NMR
(300 MHz, CDCl3): dH 1.55 (d, J¼6.9 Hz, 6H), 1.90 (s, 6H), 1.97–2.07
(m, 2H), 2.74 (t, J¼7.4 Hz, 4H), 5.19–5.29 (m, 2H), 7.18 (s, 2H), 7.26–
7.38 (m, 10H); 13C NMR (75.4 MHz, CDCl3): dC 14.7 (q), 21.7 (q), 22.8
(t), 38.5 (t), 49.1 (t), 126.3 (d), 127.5 (d), 128.7 (d), 129.4 (d), 134.2 (s),
134.7 (s), 136.3 (s), 139.9 (s), 143.0 (s), 160.8 (s); MS (EI): 554 [Mþ];
HRMS calcd for C33H34N2O2S2 554.206, found 554.205.

8332
J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
Figure 9. UV (a/b) and CD spectra (c/d) for 3 (1 mg/ml) in toluene. (a/c) solid line is gel
spectra of (a) 3o and (b) 3c in solution are also shown (dotted lines).
a 3o, dashed is gel b 3o, (b/d) dashed is gel a 3c and solid line is gel b 3c for 3. The UV/vis
4.3.2. Compound 2, 1,2-bis(20-methyl-50-{[((R)-1-cyclohexylethyl)-
amino]carbonyl}thien-30-yl)cyclopentene
4.3.4. Compound 4, 1,2-bis(50[(tert-butylamino)carbonyl]-
20-methyl-thien-30-yl)cyclopentene
As for 1, except from A (1.34 g, 3.85 mmol) and (R)-cyclohexyl-
amine (1.1 ml, 7.7 mmol). After purification by column chroma-
tography (silica gel, CH2Cl2/MeOH 60:1) and stirring in excess ether
with a few drops of MeOH, an off-white solid was obtained (0.59 g,
44%), mp 209 ꢁC (dec); 1H NMR (300 MHz, CDCl3): dH 0.93 (d,
J¼5.6 Hz, 2H),1.15–1.46 (m, 8H),1.22 (d, J¼4.4 Hz, 6H),1.62–1.77 (m,
12H), 1.94 (s, 6H), 2.00–2.10 (m, 2H), 2.78 (t, J¼7.2 Hz, 4H), 3.93–
4.02 (m, 2H), 5.52 (d, J¼9.0 Hz, 2H), 7.17 (s, 2H); 13C NMR (74.5 MHz,
CDCl3): dC 14.7 (q),17.9 (q), 22.9 (t), 26.2 (t), 26.4 (t), 29.1 (t), 38.4 (t),
43.2 (d), 49.8 (d), 129.1 (d), 134.6 (s), 134.8 (s), 136.3 (s), 139.4 (s),
161.0 (s); MS (EI): 566 [Mþ]; HRMS calcd for C33H46N2O2S2 566.300,
found 566.299.
As for 1, except from A (0.50 g, 1.44 mmol) and tert-butylamine
(0.32 ml, 3.0 mmol). After purification by column chromatography
(silica gel, CH2Cl2/MeOH 25:1) and stirring in excess ether with
a few drops of MeOH, an off-white solid was obtained (0.32 g, 48%),
mp 143 ꢁC; 1H NMR (300 MHz, CDCl3): dH 1.41 (s, 18H), 1.92 (s, 6H),
1.99–2.09 (m, 2H), 2.76 (t, J¼7.5 Hz, 4H), 5.56 (s, 2H), 7.09 (s, 2H);
13C NMR (75.4 MHz, CDCl3): dC 14.7 (q), 28.9 (q), 38.4 (t), 51.8 (t),
124.0 (s), 128.8 (d), 134.7 (s), 135.7 (s), 136.2 (s), 139.4 (s), 161.1 (s);
IR: n
1535, 1559, 1622, 2851, 2913, 2958, 3291 cmꢂ1; MS (DEI): 458
[Mþ]; HRMS calcd for C25H34S2N2O2 458.206, found 458.205.
4.3.5. Compound 5, 1,2-bis(50-[(propylamino)carbonyl]-20-methyl-
thien-30-yl)cyclopentene
As for 1, except from A (0.75 g, 2.4 mmol) and propylamine
(0.28 g, 4.8 mmol). After purification, column chromatography (silica
gel, CH2Cl2/MeOH 100:1) and stirring in excess ether with a few
drops of MeOH, an off-white solid was obtained (158 mg, 0.37 mmol,
15%), mp176.0–177.9 ꢁC; 1H NMR (500 MHz, CDCl3): dH 0.93 (t,
J¼7.5 Hz, 6H), 1.54–1.62 (m, 4H), 1.92 (s, 6H), 2.03 (m, 2H), 2.76 (t,
J¼7.2 Hz, 4H), 3.32 (m, 4H), 5.77 (m, 2H), 7.16 (s, 2H); 13C NMR
(75.4 MHz, CDCl3): dC 11.4 (q), 14.7 (q), 22.8 (t), 22.9 (t), 23.0 (t), 38.4
(t), 41.6 (t), 129.2 (d), 134.4 (s), 134.7 (s), 136.2 (s), 139.6 (s), 161.7 (s),
4.3.3. Compound 3, 1,2-bis(50-[((R)-(ꢂ)-1-methyl-3-phenylpropyl-
amino)carbonyl]-20-methyl-thien-30-yl)cyclopentene
As for 1, except from A (0.75 g, 2.4 mmol) and (R)-(ꢂ)-1-methyl-
3-phenylpropylamine (0.72 g, 4.8 mmol). After purification by col-
umn chromatography (silica gel, CH2Cl2/MeOH 100:1) and stirring
in excess ether with a few drops of MeOH, an off-white solid was
obtained (308 mg, 0.50 mmol, 21%), mp 159.4–160.8 ꢁC; 1H NMR
(300 MHz, CDCl3): dH 1.97 (s, 6H), 2.11 (m, 2H), 2.73 (t, J¼7.5 Hz, 2H),
2.83 (t, J¼7.5 Hz, 2H), 4.22 (m, 2H), 5.58 (d, J¼8.4 Hz, 2H), 7.16 (s,
2H), 7.23 (d, J¼7.2 Hz, 4H), 7.31 (m, 6H); 13C NMR (75.4 MHz,
CDCl3): dC 14.7 (q), 21.0 (q), 22.9 (t), 32.4 (t), 38.5 (t), 38.6 (t), 45.7
(d), 125.9 (d), 128.3 (d), 128.5 (d), 129.2 (d), 134.5 (s), 134.7 (s), 136.3
IR:
n
1308, 1362, 1460, 1560, 1623, 2873, 2962, 3067 cmꢂ1; MS (EI):
430 [Mþꢂ1]; HRMS calcd for C23H30S2N2O2 430.174, found 430.175.
4.3.6. Compound 6, 1,2-bis(50-[(hexylamino)carbonyl]-20-methyl-
thien-30-yl)cyclopentene
As for 1, except from A (0.500 g, 1.44 mmol) and hexylamine
(0.22 ml, 2.9 mmol). After purification, column chromatography
(s), 139.6 (s), 141.7 (s), 161.1 (s); IR:
n 1308, 1460, 1560, 1623, 2873,
2962, 3067 cmꢂ1; MS (EI): 610 [Mþ]; HRMS calcd for C37H42S2N2O2
610.269, found 610.267.

J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
8333
Figure 10. UV (a/b) and CD spectra (c/d) for 3 (3 mg/ml) in cyclohexane. (a/c) solid line is gel
vis spectra of (a) 3o and (b) 3c in solution are also shown (dotted lines).
a
3o, dashed is gel
b
3o, (b/d) dashed is gel
a
3c and solid line is gel
b
3c for 3. The UV/
(silica gel, CH2Cl2/MeOH 10:1) and stirring in excess hexane with
a few drops of MeOH, an off-white solid was obtained (0.386 g,
0.75 mmol, 52%), mp 124–127 ꢁC (dec); 1H NMR (500 MHz, CDCl3):
dH 0.87 (t, J¼6.8 Hz, 6H), 1.27–1.36 (m, 12H), 1.52–1.58 (m, 6H), 1.98
(s, 6H), 2.01–2.07 (m, 2H), 2.75–2.80 (m, 4H), 3.33–3.37 (m, 4H),
5.72 (t, J¼5.5 Hz, 2H), 7.16 (s, 2H); 13C NMR (75.4 MHz, CDCl3): dC
14.0 (q), 14.7 (q), 22.5 (t), 22.9 (t), 26.6 (t), 29.6 (t), 31.5 (t), 38.4 (t),
40.0 (t),129.2 (d),134.4 (s), 134.7 (s), 136.2 (s), 139.5 (s),161.7 (s); IR:
116 ꢁC; 1H NMR (300 MHz, CDCl3): dH 0.86 (t, J¼6.3 Hz, 6H), 1.24 (m,
60H), 1.29 (m, 4H), 1.91 (s, 6H), 1.99–2.08 (m, 2H), 2.76 (t, J¼7.5 Hz,
4H), 3.35 (q, J¼6.6 Hz, 4H), 5.77 (t, J¼5.1 Hz, J¼5.4 Hz, 2H), 7.18 (s,
2H); 13C NMR (75.4 MHz, CDCl3): dC 14.1 (q), 14.7 (q), 22.7 (t), 22.9
(t), 29.3 (t), 29.4 (t), 29.6 (t), 29.7 (t, m), 31.9 (t), 38.5 (t), 40.0 (t),
129.3 (d),134.4 (s),134.7 (s),136.3 (s),139.5 (s),161.7 (s); MS (EI): 851
[Mþ].
n
1306, 1373, 1535, 1616, 2855, 2954, 3064, 3295 cmꢂ1; MS (EI): 514
4.3.9. Compound 9, 1,2-bis(50-[(cyclohexylamino)carbonyl]-
20-methyl-thien-30-yl)cyclopentene
[Mþ]; HRMS calcd for C29H42N2O2S4 514.269, found 514.269.
As for 1, except from A (0.500 g, 1.44 mmol) and cyclohexyl-
amine (0.31 ml, 2.9 mmol). After purification, column chromatog-
raphy (silica gel, CH2Cl2/MeOH 60:1) and stirring in excess ether
with a few drops of MeOH, an off-white solid was obtained
(0.068 g, 0.13 mmol, 9%), mp 256–260 ꢁC (dec); 1H NMR (500 MHz,
CDCl3): dH 1.14–1.23 (m, 8H), 1.34–1.43 (m, 4H), 1.61 (q, J¼4.3 Hz,
4H),1.63–1.69 (m, 4H),1.91 (s, 6H),1.96 (d, 4H), 2.05 (m, 2H), 2.76 (t,
J¼7.5 Hz, 4H), 3.83–3.90 (m, 2H), 5.55 (d, J¼7.5 Hz, 2H), 7.15 (s, 2H);
13C NMR (75.4 MHz, DMSO): dC 14.2 (q), 22.3 (t), 24.9 (t), 25.2 (t),
32.5 (t), 38.3 (d), 48.2 (t), 128.6 (d), 134.0 (s), 136.0 (s), 138.5 (s),
4.3.7. Compound 7, 1,2-bis(50[(dodecylamino)carbonyl]-20-methyl-
thien-30-yl)cyclopentene
As for 1, except from A (0.200 g, 0.6 mmol) and dodecylamine
(0.26 ml, 1.2 mmol). After purification, column chromatography
(silica gel, CH2Cl2/MeOH 40:1) and stirring in excess ether with
a few drops of MeOH, an off-white solid was obtained (0.22 g, 53%),
mp 102 ꢁC; 1H NMR (300 MHz, CDCl3): dH 1.41 (t, J¼6.6 Hz, 6H), 1.24
(m, 18H), 1.56 (m, 4H), 1.92 (s, 6H), 1.97–2.07 (m, 2H), 2.77 (t,
J¼7.5 Hz, 4H), 3.35 (m, 4H), 5.77 (m, 2H), 7.17 (s, 2H); 13C NMR
(75.4 MHz, CDCl3): dC 14.1 (q),14.6 (q), 22.7 (t), 22.8 (t), 26.8 (t), 26.9
(t), 29.3 (t), 29.4 (t), 29.5 (t, 2ꢀ), 29.6 (t, 2ꢀ), 31.9 (t), 38.4 (t), 40.0
146.2 (s), 159.9 (s); IR:
n 1324, 1374, 1529, 1613, 2850, 2925, 3075,
3275 cmꢂ1; MS (EI): 510 [Mþ]; HRMS calcd for C29H38N2O2S4
510.237, found 510.237.
(t), 129.3 (d), 134.4 (s), 134.7 (s), 136.2 (s), 139.5 (s), 161.8 (s); IR:
n
1535, 1561, 1618, 2852, 2922, 3298 cmꢂ1; MS (DEI): 682 [Mþ];
HRMS calcd for C41H66S2N2O2 682.457, found 682.452.
4.3.10. Compound 10, 1,2-bis(50-[(1-cyclohexylmethylamino)-
carbonyl]-20-methyl-thien-30-yl)cyclopentene
4.3.8. Compound 8, 1,2-Bis(20-methyl-50-octyldecylcarbonyl-thien-
30-yl)cyclopentene
As for 1, except from A (0.50 g, 1.44 mmol) and octyldecylamine
(0.77 g, 2.9 mmol). After purification, column chromatography (sil-
ica gel, CH2Cl2/MeOH 40:1) and stirring in excess ether with a few
drops of MeOH, an off-white solid was obtained (0.55 g, 45%), mp
As for 1, except from A (0.450 g, 1.29 mmol) and cyclo-
hexylmethylamine (0.30 ml, 2.6 mmol). After purification, column
chromatography (silica gel, CH2Cl2/MeOH 100:1) and stirring in
excess hexane with a few drops of MeOH, an off-white solid was
obtained (0.180 g, 0.32 mmol, 51%), mp 215–217 ꢁC (dec); 1H NMR
(500 MHz, CDCl3): dH 0.94 (q, J¼11.7 Hz, 4H), 1.13–1.23 (m, 4H), 1.54

8334
J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
(s, 4H), 1.65 (d, 2H), 1.73 (d, J¼6.3 Hz, 8H), 1.94 (s, 6H), 2.04 (t,
J¼7.5 Hz, 2H), 2.75 (t, J¼7.5 Hz, 4H), 3.20 (t, J¼6.5 Hz 4H), 5.76 (t,
J¼6.0 Hz, 2H), 7.16 (s, 2H); 13C NMR (75.4 MHz, CDCl3): dC 14.7 (q),
22.9 (t), 25.8 (t), 26.4 (t), 30.8 (t), 38.0 (d), 38.4 (t), 46.1 (t), 129.3 (d),
4.3.15. Compound 15, 1,2-bis(20-methyl 50-{[((R)-(þ)-1-
naphthylethyl)amino]carbonyl}-thien-30-yl)cyclopentene
As for 1, except from A (0.500 g, 1.44 mmol) and R-(þ)-naph-
thylethylamine (0.186 ml, 2.9 mmol). After purification, column
chromatography (silica gel, CH2Cl2/MeOH 30:1) and stirring in ex-
cess ether with a few drops of MeOH, an off-white solid was
obtained (0.073 g, 0.11 mmol, 19%), mp 244–247 ꢁC (dec); 1H NMR
(500 MHz, CDCl3): dH 1.72 (d, J¼11 Hz, 6H), 1.84 (s, 6H), 1.90–2.15
(m, 2H), 2.68 (t, J¼12.3 Hz, 4H), 5.90 (d, J¼12.5 Hz, 2H), 6.03 (t,
J¼7.3 Hz, 2H), 7.09 (s, 2H), 7.40–7.52 (m, 8H), 7.81 (q, J¼16.2 Hz, 4H),
8.12 (d, J¼12.5 Hz, 2H); 13C NMR (75.4 MHz, CDCl3): dC 14.7 (q), 20.8
(q), 22.8 (t), 38.5 (t), 45.1 (d), 122.7 (d), 123.4 (d), 125.2 (d), 125.9 (d),
126.7 (d), 128.5 (d), 128.8 (d), 129.4 (d), 131.1 (s), 133.9 (s), 134.1 (s),
134.4 (s), 134.7 (s), 136.3 (s), 139.6 (s), 161.8 (s); IR:
n 1308, 1372,
1533, 1612, 2849, 2960, 3057, 3240 cmꢂ1; MS (EI): 538 [Mþ]; HRMS
calcd for C31H42N2O2S4 538.269, found 538.269.
4.3.11. Compound 11, 1,2-bis(50-(anilinocarbonyl)-20-methyl-thien-
30-yl)cyclopentene
As for 1, except from A (0.50 g, 1.44 mmol) and aniline (0.28 ml,
2.9 mmol). After purification, column chromatography (silica gel,
CH2Cl2/MeOH 50:1) and stirring in excess ether with a few drops
of MeOH, an off-white solid was obtained (0.27 g, 37%), mp 150 ꢁC
(dec); 1H NMR (300 MHz, CDCl3): dH 2.01 (s, 6H), 2.04–2.14 (m,
2H), 2.82 (t, J¼7.5 Hz, 4H), 7.12 (t, J¼7.2 Hz, 4H), 7.33 (t, J¼7.2 Hz,
4H), 7.51 (s, 2H), 7.56 (d, J¼7.8 Hz, 2H); 13C NMR (75.4 MHz,
CDCl3): dC 14.7 (q), 22.9 (t), 38.4 (t), 127.6 (d), 127.9 (d), 128.7 (d),
129.5 (d), 134.0 (s), 134.7 (s), 136.3 (s), 138.1 (s), 140.1 (s), 161.6 (s);
MS (DEI): 498 [Mþ]; HRMS calcd for C29H26S2N2O2 498.144, found
498.143.
134.6 (s), 136.2 (s), 138.0 (s), 140.0 (s), 160.7 (s); IR:
n 1334, 1371,
1530, 1615, 2842, 2947, 3050, 3280 cmꢂ1; MS (EI): 654 [Mþꢂ1];
HRMS calcd for C41H38N2O2S2 654.236, found 654.237.
Acknowledgements
The work was supported by the MSCþ dieptestrategie program
of the Zernike Institute for Advanced Materials. The authors thank
A. Kiewiet for recording of mass spectra.
4.3.12. Compound 12, 1,2-bis(50-[(benzylamino)carbonyl]-
20-methyl-thien-30-yl)cyclopentene
References and notes
This compound was prepared as described for 1, starting from A
(0.50 g, 1.44 mmol) and benzylamine (0.31 ml, 2.9 mmol). After
purification, column chromatography (silica gel, CH2Cl2/MeOH
50:1) and stirring in excess ether with a few drops of MeOH, an off-
white solid was obtained (0.18 g, 23%), mp 204 ꢁC (dec); 1H NMR
(300 MHz, CDCl3): dH 1.92 (s, 6H), 1.99–2.07 (m, 2H), 2.75 (t,
J¼7.5 Hz, 4H), 4.57 (d, J¼5.4 Hz, 4H), 6.02 (t, J¼7.3 Hz, 2H), 7.19 (s,
2H), 7.28–7.36 (m, 10H); 13C NMR (75.4 MHz, CDCl3): dC 14.8 (q),
22.9 (t), 38.4 (t), 43.9 (t), 120.1 (d), 124.4 (d), 129.0 (d), 130.2 (d),
134.5 (s), 134.9 (s), 136.6 (s), 137.7 (s), 140.9 (s), 159.9 (s); MS (DEI):
526 [Mþ]; HRMS calcd for C31H030S2N2O2 526.175, found 526.174.
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Philp, D.; Stoddart, J. F. Angew. Chem., Int. Ed. 1996, 35, 1154–1196; (c) Steed,
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Weinheim, 2001.
3. (a) van Esch, J. H.; Feringa, B. L.; de Jong, J. J. D. Responsive Molecular Gels. In
Molecular Gels; Weiss, R. G., Terech, P., Eds.; Springer: Dordrecht, The
Netherlands, 2005; ISBN 1-4020-3352-4, Chapter 26; (b) Fages, F. Low Molec-
ular Mass Gelators; Springer: Heidelberg, 2005; ISBN 3-540-25321-1; (c)
Abdallah, D. J.; Weiss, R. G. Adv. Mater. 2000, 12, 1237–1247; (d) de Loos, M.;
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J. Am. Chem. Soc. 2005, 127, 13804–13805; (b) de Jong, J. J. D.; Hania, P. R.;
Pugzlys, A.; Lucas, L. N.; de Loos, M.; Kellogg, R. M.; Feringa, B. L.; Duppen, K.;
van Esch, J. H. Angew. Chem., Int. Ed. 2005, 2373–2376; (c) de Jong, J. J. D.;
Lucas, L. N.; Kellogg, R. M.; van Esch, J. H.; Feringa, B. L. Science 2004, 304, 278–
281; (d) Lucas, L. N.; van Esch, J.; Feringa, B. L.; Kellogg, R. M. Chem. Commun.
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6. (a) Brizard, A.; Oda, R.; Huc, I. Top. Curr. Chem. 2005, 256, 167–218; (b) Ihara, H.;
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Langmuir 2002, 18, 7120–7123; (c) Koga, T.; Matsuoka, M.; Higashi, N. J. Am.
Chem. Soc. 2005, 127, 17596–17597; (d) Hirst, A. R.; Huang, B.; Castelletto, V.;
Hamley, I. W.; Smith, D. K. Chem.dEur. J. 2007, 13, 2180–2188; (e) Hirst, A. R.;
Smith, D. K.; Feiters, M. C.; Geurts, H. P. M. Chem.dEur. J. 2004, 10, 5901–5910;
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Chem.dEur. J. 2003, 9, 5567–5580; (g) Iwaura, R.; Shimizu, T. Angew. Chem.,
Int. Ed. 2006, 25, 4601–4604.
4.3.13. Compound 13, 1,2-bis(50-[((p)-tert-butylphenylamino)-
carbonyl]-20-methyl-thien-30-yl)cyclopentene
As for 1, except from A (0.500 g, 1.44 mmol) and (p)-tert-butyl-
phenylamine (0.37 ml, 2.9 mmol). After purification, column chro-
matography (silica gel, CH2Cl2/MeOH 30:1) and stirring in excess
ether with a few drops of MeOH, a white solid was obtained
(0.092 g, 0.15 mmol, 26%), mp 160–174 ꢁC (dec); 1H NMR (500 MHz,
CDCl3): dH 1.26–1.31 (m,18H), 2.00 (s, 6H),1.96–2.15 (m, 2H), 2.79 (t,
J¼7.5 Hz, 4H), 7.29 (s, 2H), 7.32 (q, J¼3.7 Hz, 4H), 7.46 (q, J¼6.8 Hz,
4H); 13C NMR (75.4 MHz, CDCl3): dC 14.8 (q), 22.9 (t), 31.3 (q), 34.4
(t), 38.3 (s), 119.9 (d), 125.9 (d), 130.0 (d), 134.6 (s), 134.9 (s), 1345.0
(s), 136.5 (s), 140.7 (s), 147.4 (s), 159.7 (s); IR:
n 1319, 1362, 1526,
1646, 2868, 2962, 3057, 3387 cmꢂ1; MS (EI): 610 [Mþ]; HRMS calcd
for C37H42N2O2S2 610.269, found 610.268.
4.3.14. Compound 14, 1,2-bis(50-[((m)-(m)-di-tert-butylphenyl-
amino)carbonyl]-20-methyl-thien-30-yl)cyclopentene
7. For 2 only the R- and S-enantiomer and for 3 only the R-enantiomer were pre-
pared. However, for 1 the racemic, R- and S-enantiomer of the compound, which
were examined previously5c were prepared. For both 1 and 2 the S-enantiomer
showed similar (but as expected opposite) behaviour to the R-enantiomers. For
clarity only the R-enantiomer will be discussed in the present work.
8. Kaminski, Z. J. Tetrahedron Lett. 1985, 26, 2901–2904.
As for 1, except from A (0.500 g, 1.44 mmol) and (2,5)-di-tert-
butylphenylamine (0.237 mg, 2.9 mmol). After purification, column
chromatography (silica gel, CH2Cl2/MeOH 30:1) and stirring in ex-
cess ether with a few drops of MeOH, an off-white solid was
obtained (0.039 g, 0.05 mmol, 7%), mp 214–215 ꢁC (dec); 1H NMR
(500 MHz, DMSO): dH 1.24–1.31 (m, 36H), 1.93 (s, 6H), 2.08 (m, 2H),
2.84 (t, J¼8.7 Hz, 4H), 7.13 (s, 2H), 7.57 (s, 4H), 7.79 (s, 2H), 9.79 (s,
2H); 13C NMR (188.5 MHz, DMSO): dC 13.8 (q), 22.1 (t), 30.7 (q), 30.8
(q), 30.8 (q), 34.1 (t), 38.0 (s), 114.3 (d), 114.4 (s), 114.4 (d), 116.4 (d),
116.8 (s), 117.1 (d), 129.1 (s), 129.3 (d), 133.9 (s), 135.5 (s), 135.6 (s),
9. Lucas, L. N.; de Jong, J. J. D.; Kellog, R. M.; van Esch, J. H.; Feringa, B. L. Eur. J. Org.
Chem. 2003, 155–166.
10. For electrochemical properties compounds 1–13 show very similar behavior.
For all compounds in the open state an irreversible wave at 1.29 (3) V (vs SCE)
was observed, which did not result in switching to the closed form, with the
exception of 11o, where the oxidation falls outside the potential window of
methanol. In the closed state all compounds, including 11c, show a quasi re-
versible oxidation at 0.74 (2) V (vs SCE) and an irreversible oxidation at 0.83
(2) V (vs SCE).
137.6 (s), 139.3 (s), 150.1 (s), 158.9 (s); IR:
n 1322, 1361, 1513, 1630,
2865, 2961, 3079, 3249 cmꢂ1; MS (EI): 723 [Mþꢂ1]; HRMS calcd for
11. 30–120 s after cooling to rt, and even faster by quenching in either ice-water
C
45H58N2O2S2 722.393, found 722.394.
(0 ꢁC), cold methanol (ꢂ40 ꢁC) or even liquid nitrogen (ꢂ192 ꢁC).

J.J.D. de Jong et al. / Tetrahedron 64 (2008) 8324–8335
8335
12. Zweep, N. Ph.D. thesis, University of Groningen: Groningen, The Netherlands,
2006.
16. Irradiation of 3o in chloroform-d1 and in hot toluene showed racemic 3c with
signals for the thiophene proton matching those of the gels.
13. The zero point crossing on the y-axis is obsecured by the solvent absorp-
17. For the spectrum of 1o in toluene see Ref. 5c.
tion, but extrapolation of the lines point to
a
common CD minimum at
18. The absorbance between 325–380 nm is close to the limit of the dynamic range
l
¼297 nm.
of the spectrophotometer; the unusual shape of the CD signal for gel
to the high absorbance.
b 2c is due
14. All samples were prepared similarly, although at different minimal gelation
concentrations according to Table 1. The concentrations needed for gelation of
2o in benzene, tetralin, 1,4-dioxane and butylacetate are too high to allow for
measurement of CD spectra.
15. As for 1o, the zero point crossing on the y-axis is obsecured by the solvent
absorption for 2o, but extrapolation of the lines point to a common CD mini-
19. For redox properties of related diarylcyclopentenes in solution, see: (a) Browne,
W. R.; de Jong, J. J. D.; Kudernac, T.; Walko, M.; Lucas, L. N.; Uchida, K.; van Esch,
J. H.; Feringa, B. L. Chem.dEur. J. 2005, 11, 6414–6429; (b) Browne, W. R.; de
Jong, J. J. D.; Kudernac, T.; Walko, M.; Lucas, L. N.; Uchida, K.; van Esch, J. H.;
Feringa, B. L. Chem.dEur. J. 2005, 11, 6430–6441.
mum at
l¼295 nm.
20. Terech, P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133–3159.