Switching Process Consisting of Three Isomeric States of an Azobenzene Unit

Article abstract of DOI:10.1021/jacs.7b05316

Azobenzene and its derivatives are among the most commonly used switching units in organic chemistry. The switching process consists of two states, in which the trans isomer has a stretched and the cis isomer a compact form. Here, we have designed a syste

Full text of DOI:10.1021/jacs.7b05316

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Article
Switching Process Consisting of Three Isomeric States of an Azobenzene Unit
Abdulselam Adam, and Gebhard Haberhauer
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 22 Jun 2017
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Switching Process Consisting of Three Isomeric States of an Azobenzene Unit
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Abdulselam Adam† and Gebhard Haberhauer*†
† Institut für Organische Chemie, Universität DuisburgꢀEssen, Universitätsstr. 7, Dꢀ45117
Essen, Germany
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Eꢀmail: gebhard.haberhauer@uniꢀdue.de
ABSTRACT: Azobenzene and its derivatives are one of the most commonly used switching
units in organic chemistry. The switching process consists of two states, in which the trans
isomer has a stretched and the cis isomer a compact form. Here, we have designed a
system in which all isomeric states of an azobenzene moiety (trans → cisꢀ(M) → cisꢀ(P)) are
passed step by step. The first step involves the change in the distance between the benzene
units, which is common for azobenzene derivatives; in the second step an inversion of the
helicity (M → P) of the cis azobenzene unit takes place; the third step leads back to the
stretched trans isomer. This switching cycle is achieved by coupling the azobenzene unit
with two chiral clamps and with a further azobenzene switching unit.
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Introduction
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Photochromic molecules that can be reversibly switched between two isomers of different
structures are of great interest for the development of molecular hostꢀguest systems and
molecular machines.1ꢀ4 One of the most commonly used switching unit is azobenzene and its
derivatives:5ꢀ16,The trans isomer has a stretched and the cis isomer a compact form. Usually,
the trans → cis isomerization takes place by UV light and the cis → trans back relaxation by
visible light or heat.5,17 The reasons for the popularity of azobenzene derivatives as a
switching units are the high reversibility, the simple synthesis and the high photostability,
which allows a large number of switching cycles. The high range of variation in excitation
wavelength, stability and movement pattern are other crucial features of these compounds.
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Scheme 1. a) Lightꢀinduced switching process of azobenzene (1) consisting of the two
states: transꢀ1 and cisꢀ1 (racemate). b) Lightꢀinduced switching processes of a chiral
azobenzene cage consisting of the three states transꢀ2, cisꢀ(M)ꢀ2 and cisꢀ(P)ꢀ2. Compound 2
shows – additionally to the azobenzene unit – a further switching element (blue or green
rectangle); the black ellipses in compound 2 represents the chiral clamp 3 (for the detailed
chemical structure of compounds 2 and 3 see Scheme 2).
The use of suitable substituents on the benzene units allows the variation of the thermal cis
→ trans back isomerization,18 the orthogonal switching of azobenzene double switches19 and
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the switching with visible light.20ꢀ26 The latter feature is of particular importance for in vivo
switching processes27 or those of biomolecules28ꢀ29. Recently, it has also been shown that the
cis → trans back isomerization can be accelerated by electrochemical catalysis.30 The form
of the motion (rotation around the N=Nꢀbond or inversion on a nitrogen atom) can be
controlled by incorporation into polycyclic structures.31ꢀ33 A closer look at the switching
process of azobenzene (1) shows that the trans → cis isomerization implies not only a
structural change but also a generation of helical chirality: the cis isomer is an enantiomeric
pair of cisꢀ(M)ꢀ1 and cisꢀ(P)ꢀ1 (Scheme 1a). In the literature there are some examples in
which the conformation of the cis or the trans isomers is controlled by chiral bridges.34ꢀ37,33,38
But a system in which all three isomers are incorporated into a switching cycle consisting of
three states has to the best of our knowledge not yet been described in the literature. The
design of such a system would be a very worthwhile goal and would add invaluable insight
into the rich photophysical processes and properties of azobenzene based molecular
switches and machines. The process would consist on the one hand of a switching between
the stretched and the compact form (trans and cis) and on the other hand of a switching
between the helicities of the cis isomers (M and P arrangement). Here we describe the
synthesis and the investigation of a system which can adopt all three different states of an
azobenzene unit. In the following we will call this system as triple switch.
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Results and Discussion
a) Concept and synthesis of the triple switch
For the design of a switching system, which can adopt all three different states of an
azobenzene unit, a dilemma arises: In order to switch from the trans isomer to only one of
the cis isomers (for example: into the cis-(M) isomer of the azo switch 2 in Scheme 1b), it is
necessary to implement a chiral unit, which energetically excludes the formation of the cisꢀ
(P) isomer. However, this chiral induction – which is necessary for the first step – prevents
the second switching process to the cisꢀ(P) isomer. In order to solve this problem, the
introduction of a second switching unit into the system 2 is absolutely necessary. This should
also be present in a stretched (blue rectangle in Scheme 1b) or in a compact form (green
rectangle in Scheme 1b). The switching cycle should proceed as following: 1) In the trans
isomer of 2, the trans azobenzene unit is connected to two chiral clamps (black ellipses in
Scheme 1b). These are subsequently necessary for the chirality induction in the formation of
the cisꢀ(M) isomer. However, due to their chirality they also cause, that the trans azobenzene
unit is fixed at a certain angle α (α < 90°; Scheme 1b) relative to the lower chiral clamp. The
second switching element (blue rectangle in Scheme 1b) is present in a stretched form.
Therefore, the distance d between the clamps is large. 2) In the cisꢀ(M) isomer, the
azobenzene unit and the second switching element are present in the compact form; the
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distance between the clamps d' is accordingly reduced considerably compared to d in the
trans isomer. The chiral induction of the two clamps leads to the fact, that the cisꢀ(M)
conformation of the azobenzene is energetically much more preferred than the cisꢀ(P)
conformation. 3) In order to obtain the cisꢀ(P) conformation of 2, the following trick is applied:
The second switching element is switched from the compact (green) to the stretched state
(blue), whereby the distance d'' between the clamps becomes larger (d'' > d'). The greater
distance favors the cisꢀ(P) conformation of the azobenzene unit. This assumption seems to
be irritating at first glance, because cisꢀ(M) and cisꢀ(P) azobenzene have the same sizes.
However, the spatial fixation of the azobenzene unit and the relative position to further units
(e.g. the linking sites) must also be taken into account. This can be easily illustrated by
holding one of the two benzene units of cisꢀ(M) and cisꢀ(P) azobenzene (1) at a fixed angle α
(α < 90°) relative to the plane a (see Scheme 2a and Figure S1). The distance of plane a to
the second plane b, which also touches the azobenzene, is significantly larger for the cisꢀ(P)
isomer than for the cisꢀ(M) isomer (d'' > d').
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Hence, if the distance of the chiral clamps in 2 is increased by the second switching element
(Scheme 1b), the actual preference of the chiral clamps for the cisꢀ(M) conformation is
reversed. In this step, an inversion of the helicity of the cis azobenzene unit occurs.
Scheme 2. a) The spatial fixation of an azobenzene unit relative (α <90 °) to plane a leads to
different distances (d'' > d') to the second plane b for the two enantiomers cisꢀ(M) and cisꢀ(P)
azobenzene (1). Both planes (a and b) should touch the azobenzene unit. b) Synthesis of the
chiral azobenzene cage trans,transꢀ2. Reaction conditions: i) Cs2CO3, CH3CN, ꢀ, 27%.
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Looking for suitable chiral clamps and a second switching element, we have carried out a
series of preliminary calculations. Among the different chiral systems we have used for
chirality induction,39ꢀ41 the imidazoleꢀcontaining clamp 342 was the one with the greatest
prospect of success (Scheme 2b). This clamp has already been used in many other
unidirectional switching processes.43ꢀ46 As a second switching element, we have decided for
a further azobenzene unit. The advantage of azobenzene is the already mentioned
reversibility, easy switchability and the great structural difference between the isomers. The
disadvantage of the use of azobenzene as a second switch is the indistinguishability of the
two switching units. Thus, the six possible states in which the chiral azobenzene cage 2 can
be present are: trans,trans, cis,transꢀ(M), cis,transꢀ(P), cis,cisꢀ(M,M), cis,cisꢀ(M,P) and
cis,cisꢀ(P,P). The states of the desired threeꢀstep switching process are: trans,trans,
cis,transꢀ(P) and cis,cisꢀ(M,M).
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The synthesis of the switching system 2 takes places from the chiral clamp 342 and the
dibromide 447 (Scheme 2b). Both can be synthesized in only few steps from commercially
available compounds. After the synthesis of 2, three isomers are obtained which are
according to the HPLC chromatogram present in the ratio of 71:27:2 (see Figure S19).
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According to the symmetry of the signals in the H NMR spectra, these are the isomers:
trans,trans (71%), cis,trans (27%) and cis,cis (2%). Using NMR spectroscopy (1H NMR and
NOESY spectra), a determination of the conformation (M or P) of the cis azobenzene units
could not be achieved (see Figures S10ꢀ15).
b) Structural investigation of the states of the triple switch 2
To clarify whether the system has the desired switching properties, a series of isomers were
optimized by means of the B3LYP48ꢀ50 functional and the 6ꢀ31G*51ꢀ52 basis set (Figures 1 and
S2). Subsequently, the energies of the isomers were computed by using B3LYPꢀD353ꢀ54 and
the basis set def2ꢀTZVP55ꢀ56. The calculations show that the distance between the two chiral
clamps strongly depends on the configuration (trans or cis) and also on the conformation (M
or P). The size of trans,transꢀ2 (14.7 Å) is significantly larger than that of cis,cisꢀ(P,P)ꢀ2 (12.1
Å) and cis,cisꢀ(M,M)ꢀ2 (10.7 Å). The difference between the two cis,cis isomers matches well
with the above mentioned hypothesis for the different space requirements of the cis isomers
(Scheme 2a and Figure S1). The size of cis,transꢀ(P)ꢀ2 and cis,transꢀ(M)ꢀ2 is about 12.3 Å
and is approximately as large as that of cis,cisꢀ(P,P)ꢀ2 (12.1 Å). This means that the cisꢀ(M)
moiety differs strongly, whereas the cisꢀ(P) moiety differs only slightly from its "ideal"
geometry. The calculated energy differences verify the success of this strategy: cis,cisꢀ
(M,M)ꢀ2 is much more stable than cis,cisꢀ(P,P)ꢀ2 (42.7 kJ/mol), whereas the cis,trans
isomers show a reversed preference. However, the difference between cis,transꢀ(P)ꢀ2 and
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cis,transꢀ(M)ꢀ2 is with 2.0 kJ/mol relatively small. A "mixed" cis,cisꢀ(M,P) isomer could not be
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Figure 1. Molecular structures of trans,transꢀ2 (left), cis,cisꢀ(M,M)ꢀ2 (middle) and cis,transꢀ
(P)ꢀ2 (right) calculated with B3LYP/6ꢀ31G*. All hydrogen atoms are omitted for the sake of
clarity.
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Figure 2. UV spectra of trans,transꢀ2 (blue), cis,transꢀ2 (red) and cis,cisꢀ2 (green) in
methanol/water (95/5) (c = 1.0 × 10ꢀ5
).
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For a more detailed structural investigation, the single HPLC peaks were collected and
measured within few minutes by means of UV and CD spectroscopy. The fact that the
collected fractions are indeed the pure isomers could be confirmed as following: After
collection and a waiting time of about 20 minutes, HPLC chromatograms of the single
fractions were recorded. These chromatograms show that the isomers are present in purities
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of 91ꢀ98% (see Figures S16ꢀ18). The UV and CD spectra of the three isomers are depicted
in Figures 2 and 3. As anticipated, the trans,trans isomer exhibits the highest absorption
band at 330 nm and the cis,cis isomer the lowest one (Figure 2). This absorption band
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corresponds to the
π→π* transition and its change is typical for isomerization of azobenzene
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derivatives. On the other side, the n→
π* transition at ca. 450 nm is more pronounced for the
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cis,cis isomer than for the other isomers. This is consistent with the UV spectra of other
simple alkylꢀsubstituted cis azobenzenes. The isosbestic point for the three isomers can be
found at 284 nm.
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Figure 3. a) CD spectra of trans,transꢀ2 (blue), cis,transꢀ2 (red) and cis,cisꢀ2 (green) in
methanol/water (95/5) (c = 1.0 × 10ꢀ5
). b) By means of TDꢀB3LYP/6ꢀ31G* calculated CD
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spectra of trans,transꢀ2 (blue), cis,cisꢀ(M,M)ꢀ2 (green) and cis,transꢀ(P)ꢀ2 (red). c) By means
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of TDꢀB3LYP/6ꢀ31G* calculated CD spectra of cis,cisꢀ(P,P)ꢀ2 (green) and cis,transꢀ(M)ꢀ2
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(red).
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A major advantage in the interpretation of CD spectra of simple alkylꢀsubstituted cis
azobenzenes is the fact, that the conformation (M or P) can be directly identified from the
sign of the Cotton effect at 450 nm. This is due to the fact, that this area is dominated by only
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one transition (n→π*). Previous investigations have shown that the cisꢀ(M) isomer has a
positive and the cisꢀ(P) isomer exhibits a negative Cotton effect in this region (see also
Figure S3).34
For a better assignment and interpretation, the CD spectra of trans,transꢀ2, cis,transꢀ(M)ꢀ2,
cis,transꢀ(P)ꢀ2, cis,cisꢀ(M,M)ꢀ2 and cis,cisꢀ(P,P)ꢀ2 were calculated by means of timeꢀ
dependent density function theory57 (TDꢀB3LYP) and the 6ꢀ31G* basis set (Figure 3). A
comparison of the simulated and the experimentally determined CD spectrum of trans,transꢀ
2 shows a good agreement between theory and experiment (Figure 3). The spatial fixation of
the two trans azobenzene units can be recognized by the positive Cotton effect for the n→π*
transition and especially by the intense CD pair at about 340 nm. For the interpretation, the
exciton chirality method can be applied:58 Because of the positive band at a higher
wavelength (350 nm) and the negative band at a lower wavelength (315 nm), the two trans
azobenzene units are fixed at an angle
α < 90° relative to the chiral clamps (Figure S1).
The experimentally determined spectrum of the cis,trans isomer matches only with the
simulated spectrum of cis,transꢀ(P)ꢀ2, but not with that of cis,transꢀ(M)ꢀ2. For the
experimentally determined and the simulated spectra of cis,transꢀ(P)ꢀ2 the Cotton effect for
the n→π* transition is negative and for the π→π* transitions positive. The latter one can be
find in the area at about 320 nm. In comparison, cis,transꢀ(M)ꢀ2 has a strongly positive
Cotton effect at 500 nm and a negative Cotton effect at 300 nm. The CD spectrum of cis,cisꢀ
2 can be interpreted analogously: The Cotton effects for the n→π* and the π→π* transitions
clearly indicate the presence of the cis,cisꢀ(M,M) isomer, while the cis,cisꢀ(P,P) can be
excluded.
c) Investigation of the Switching Process
The switching processes were investigated by means of UV and NMR spectroscopy as well
as with HPLC in methanol as solvent (Figures 4, S4ꢀS7 and S19ꢀS23).
The UV spectra obtained during the switching processes are as anticipated: The UV
spectrum of the triple switch 2 after UV irradiation with
cis,cis isomer (Figures 2 and S23). After irradiation with visible light (
mentioned increase of the * transition at 330 nm is observed and the spectrum is similar
λ
= 365 nm resemble that of the
λ
= 530 nm) the above
π→π
to the UV spectrum of the isolated cis,trans isomer. A subsequent irradiation with UV light of
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the wavelength
λ
= 405 nm results in an even more pronounced increase of the π→π* band
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at 330 nm. This spectrum matches with the UV spectrum of the trans,trans isomer (Figures 2
and S23). Using UV spectroscopy, a quantitative determination of the ratio of the three
isomers is not reasonable. For this purpose, NMR spectroscopy and HPLC are more
appropriate. However, the determination of the isomer ratios by NMR studies was difficult, as
the relevant peaks of the single isomers partly overlap with other peaks. Due to the multitude
of signals in the 1H NMR spectrum of 2, we wanted to check if all signals belong to the triple
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switch 2. Therefore, compound 2 was dissolved in C2D2Cl4 (c = 10−2
M) and heated stepwise
to a temperature of 120 °C (Figure 4). Beside a slight upfield shift, all signals except those
belonging to the trans,trans isomer disappeared. After cooling down to 20 °C, only the
signals of the thermodynamic most stable the trans,trans isomer are present (Figure 4).
Hence, the multitude of signals in the 1H NMR spectrum indeed can be assigned to the triple
switch 2.
Figure 4. Section from the 1H NMR spectra (protons Hb and Hc; for assignment see Scheme
1) of the chiral cage 2 at 500 MHz in C2D2Cl4 (10−2
M) in the temperature range from 20 (a) to
120 °C (f) in steps of 20 °C and after cooling to 20 °C (g).
The switching process was investigated by NMR spectroscopy and HPLC in methanol.
1
Please note that the H NMR signals in methanol (especially the signals of the trans,trans
isomer) are strongly shifted compared to those measured in C2D2Cl4 (Figures 4ꢀ5). The ratio
for the three isomers determined by NMR differs from that obtained by HPLC (Figures 5, S4ꢀ
S7 and S19ꢀS22). This discrepancy is due to the fact that the isomerization caused by the
used LEDs is dependent on the concentration. The lower the concentration of the
azobenzene, the higher is the switching rate (Figures S6 and S7). As the HPLC experiments
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were carried out at significantly lower concentrations (10ꢀ4
M), higher degrees of
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isomerization were obtained. Hereinafter, only the values obtained by HPLC are discussed.
In order to obtain the ratios for the three isomers by HPLC as accurate as possible, the
wavelength of the detector was set to 284 nm. This is the isosbestic point for the three
isomers (Figure 2).
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8.00
ppm (t1)
7.50
7.00
1
Figure 5. Section from the H NMR spectra (protons Hb and Hc) of the chiral azobenzene
cage 2: (a) after synthesis, (b) after UV irradiation with = 365 nm, (c) after irradiation with
visible light ( = 530 nm) and (d) after subsequent UV irradiation with = 405 nm (MeOD,
500 MHz, 10ꢀ2
). The protons Hb and Hc of the isomers trans,transꢀ2 (blue), cis,cisꢀ(M,M)ꢀ2
(green) and cis,transꢀ(P)ꢀ2 (red) are marked.
λ
λ
λ
M
After the synthesis, the chiral azobenzene cage 2 is predominantly present as trans,trans
isomer (ratio of trans,trans / cis,transꢀ(P) / cis,cisꢀ(M,M) amounts to 71:27:2 see Figure S19).
The first step in the switching cycle is the irradiation with UV light of the wavelength
nm, which leads to an isomerization to the cis,cisꢀ(M,M) isomer. A trans,trans / cis,transꢀ(P) /
cis,cisꢀ(M,M) ratio of 4:29:68 is achieved in the photostationary state at = 365 nm (Figure
λ = 365
λ
S20). The finding of the optimal trigger for the second step of the switching cycle, in which
one azobenzene unit is switched from cis to trans and the second azobenzene unit
undergoes an inversion of its helicity, was difficult. The best results are obtained when the
solution is irradiated with visible light of the wavelength
λ = 530 nm for only a few seconds.
The ratio trans,trans / cis,transꢀ(P) / cis,cisꢀ(M,M) is then changed to 20:66:14 (Figure S21).
The third step of the switching cycle leads back to the initial state trans,transꢀ2 and is
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realized by irradiation with UV light of the wavelength
λ
= 405 nm. In the photostationary
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state at
λ
= 405 nm, a trans,trans / cis,transꢀ(P) / cis,cisꢀ(M,M) ratio of 80:18:3 is achieved
6
7
(Figure S22).
Experiments for the determination of the halfꢀlife of the energetically most unfavorable
cis,cisꢀ(M,M) isomer have shown that this has a value of 14 days (346 h) at 5 °C and 69 h at
25 °C (Figures S8, S9 and S24ꢀS26). Accordingly, the single isomers are stable for a long
time and rapid back relaxation does not occur. Here, the cis,cis isomer is slowly converted to
the cis,trans isomer and the latter is obtained with a higher ratio than by the irradiation with
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visible light of the wavelength
λ = 530 nm (Figure S8ꢀS9 and S24). These results show that
the cis,trans isomer can also be obtained from the cis,cis isomer by a certain temperature
increase. The amount of the trans,trans isomer remains unchanged at about 8%, even after
one month after irradiation.
Conclusion
In summary, we have shown that we have designed a system having a switching cycle that
passes through all three isomeric azobenzene states (trans → cisꢀ(M) → cisꢀ(P)). This was
achieved by means of two chiral clamps and the introduction of a further azobenzene
switching unit. As the system can be synthesized in only few steps, a further substitution of
the azobenzene unit should be possible. Therefore, it should be possible in the future to
switch both the distance between two substituents and the relative position of the two units in
space (inversion of the helicity). As compound 2 passes through a cycle of states showing
reversed helicity, it is per se a chiroptical switch with inverted Cotton effects at 450 nm.
Furthermore, modification of the substituents at the azobenzene unit should allow the design
of molecular motors – which pass through the three isomeric states of the azobenzene – and
of lightꢀinduced selective hosting of different chiral guests.
Acknowledgements
This work was generously supported by the Deutsche Forschungsgemeinschaft (DFG; HA
2973/9ꢀ1). The authors thank Katrin Steiger for her help in recording the HPLC
chromatograms.
Supporting Information
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Synthesis of the new compounds, H NMR and 13C NMR spectra of the new compounds,
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calculated molecular structures, NMR, HPLC, and UV spectra, cartesian coordinates and
absolute energies of all calculated compounds.
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References
(1) Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007, 46, 72ꢀ191.
(2) Molecular Switches 2nd ed.; Feringa, B. L., Browne, W. R., Eds.; WileyꢀVCH: Weinheim,
2011.
(3) ErbasꢀCakmak, S.; Leigh, D. A.; McTernan, C. T.; Nussbaumer, A. L. Chem. Rev. 2015,
115, 10081ꢀ10206.
(4) Qu, D.ꢀH.; Wang, Q.ꢀC.; Zhang, Q.ꢀW.; Ma, X.; Tian, H. Chem. Rev. 2015, 115, 7543ꢀ
7588.
(5) Rau, H. Angew. Chem., Int. Ed. 1973, 12, 224ꢀ235.
(6) Mathews, M.; Zola, R. S.; Hurley, S.; Yang, D.ꢀK.; White, T. J.; Bunning, T. J.; Li, Q. J.
Am. Chem. Soc. 2010, 132, 18361ꢀ18366.
(7) Beharry, A. A.; Woolley, G. A. Chem. Soc. Rev. 2011, 40, 4422ꢀ4437.
(8) Bandara, H. M.; Burdette, S. C. Chem. Soc. Rev. 2012, 41, 1809ꢀ1825.
(9) Merino, E.; Ribagorda, M. Beilstein J. Org. Chem. 2012, 8, 1071ꢀ1090.
(10) Natali, M.; Giordani, S. Chem. Soc. Rev. 2012, 41, 4010ꢀ4029.
(11) Wang, Y.; Urbas, A.; Li, Q. J. Am. Chem. Soc. 2012, 134, 3342ꢀ3345.
(12) Li, Y.; Wang, M.; White, T. J.; Bunning, T. J.; Li, Q. Angew. Chem. Int. Ed. 2013, 52,
8925ꢀ8929.
(13) Sun, R.; Xue, C.; Ma, X.; Gao, M.; Tian, H.; Li, Q. J. Am. Chem. Soc. 2013, 135, 5990ꢀ
5993.
(14) Abendroth, J. M.; Bushuyev, O. S.; Weiss, P. S.; Barrett, C. J. ACS Nano 2015, 9, 7746ꢀ
7768.
(15) Fihey, A.; Perrier, A.; Browne, W. R.; Jacquemin, D. Chem. Soc. Rev. 2015, 44, 3719ꢀ
3759.
(16) Bisoyi, H. K.; Li, Q. Chem. Rev. 2016, 116, 15089ꢀ15166.
(17) Griffiths, J. Chem. Soc. Rev. 1972, 1, 481ꢀ493.
(18) Schweighauser, L.; Strauss, M. A.; Bellotto, S.; Wegner, H. A. Angew. Chem., Int. Ed.
2015, 54, 13436ꢀ13439.
(19) Zhao, F.; Grubert, L.; Hecht, S.; Bléger, D. Chem. Commun. 2017, 53, 3323ꢀ3326.
(20) Siewertsen, R.; Neumann, H.; BuchheimꢀStehn, B.; Herges, R.; Näther, C.; Renth, F.;
Temps, F. J. Am. Chem. Soc. 2009, 131, 15594ꢀ15595.
(21) Beharry, A. A.; Sadovski, O.; Woolley, G. A. J. Am. Chem. Soc. 2011, 133, 19684ꢀ
19687.
12
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Journal of the American Chemical Society
1
2
3
4
5
(22) Bleger, D.; Schwarz, J.; Brouwer, A. M.; Hecht, S. J. Am. Chem. Soc. 2012, 134, 20597ꢀ
20600.
(23) Wegner, H. A. Angew. Chem., Int. Ed. 2012, 51, 4787ꢀ4788.
(24) Bushuyev, O. S.; Tomberg, A.; Friscic, T.; Barrett, C. J. J. Am. Chem. Soc. 2013, 135,
12556ꢀ12559.
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(25) Knie, C.; Utecht, M.; Zhao, F.; Kulla, H.; Kovalenko, S.; Brouwer, A. M.; Saalfrank, P.;
Hecht, S.; Bléger, D. Chem. Eur. J. 2014, 20, 16492ꢀ16501.
(26) Konrad, D. B.; Frank, J. A.; Trauner, D. Chem. Eur. J. 2016, 22, 4364ꢀ4368.
(27) Samanta, S.; Beharry, A. A.; Sadovski, O.; McCormick, T. M.; Babalhavaeji, A.;
Tropepe, V.; Woolley, G. A. J. Am. Chem. Soc. 2013, 135, 9777ꢀ9784.
(28) Kienzler, M. A.; Reiner, A.; Trautman, E.; Yoo, S.; Trauner, D.; Isacoff, E. Y. J. Am.
Chem. Soc. 2013, 135, 17683ꢀ17868.
(29) Schweighauser, L.; Häussinger, D.; Neuburger, M.; Wegner, H. A. Org. Biomol. Chem.
2014, 12, 3371ꢀ3379.
(30) GouletꢀHanssens, A.; Utecht, M.; Mutruc, D.; Titov, E.; Schwarz, J.; Grubert, L.; Bléger,
D.; Saalfrank, P.; Hecht, S. J. Am. Chem. Soc. 2017, 139, 335ꢀ341.
(31) Rau, H.; Lueddecke, E. J. Am. Chem. Soc. 1982, 104, 1616ꢀ1620.
(32) Pancur, T.; Renth, F.; Temps, F.; Harbaum, B.; Kruger, A.; Herges, R.; Nather, C. Phys.
Chem. Chem. Phys. 2005, 7, 1985ꢀ1989.
(33) Haberhauer, G.; Kallweit, C.; Wölper, C.; Bläser, D. Angew. Chem., Int. Ed. 2013, 52,
7879ꢀ7882.
(34) Haberhauer, G.; Kallweit, C. Angew. Chem., Int. Ed. 2010, 49, 2418ꢀ2421.
(35) Takaishi, K.; Kawamoto, M.; Tsubaki, K.; Furuyama, T.; Muranaka, A.; Uchiyama, M.
Chem. Eur. J. 2011, 17, 1778ꢀ1782.
(36) Takaishi, K.; Muranaka, A.; Kawamoto, M.; Uchiyama, M. J. Org. Chem. 2011, 76, 7623ꢀ
7628.
(37) Takaishi, K.; Muranaka, A.; Kawamoto, M.; Uchiyama, M. Org. Lett. 2011, 14, 276ꢀ279.
(38) Núñez, I.; Merino, E.; Lecea, M.; Pieraccini, S.; Spada, G. P.; Rosini, C.; Mazzeo, G.;
Ribagorda, M.; Carreño, M. C. Chem. Eur. J. 2013, 19, 3397ꢀ3406.
(39) Haberhauer, G.; Oeser, T.; Rominger, F. Chem. Commun. 2005, 2799ꢀ2801.
(40) Pintér, Á.; Haberhauer, G.; HylaꢀKryspin, I.; Grimme, S. Chem. Commun. 2007, 3711ꢀ
3713.
(41) Pintér, Á.; Haberhauer, G. Synlett 2009, 3082ꢀ3098.
(42) Haberhauer, G. Angew. Chem., Int. Ed. 2007, 46, 4397ꢀ4399.
(43) Haberhauer, G. Angew. Chem., Int. Ed. 2008, 47, 3635ꢀ3638.
(44) Haberhauer, G. Angew. Chem., Int. Ed. 2010, 49, 9286ꢀ9289.
(45) Haberhauer, G. Angew. Chem., Int. Ed. 2011, 50, 6415ꢀ6418.
13
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Page 14 of 15
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2
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4
5
(46) Burkhart, C.; Haberhauer, G. Eur. J. Org. Chem. 2017, 1308ꢀ1317.
(47) Sudesh Kumar, G.; Savariar, C.; Saffran, M.; Neckers, D. Macromolecules 1985, 18,
1525ꢀ1530.
6
7
8
(48) Becke, A. D. Phys. Rev. A 1988, 38, 3098ꢀ3100.
9
(49) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785ꢀ789.
(50) Miehlich, B.; Savin, A.; Stoll, H.; Preuss, H. Chem. Phys. Lett. 1989, 157, 200ꢀ206.
(51) Ditchfield, R.; Hehre, W. J.; Pople, J. A. J. Chem. Phys. 1971, 54, 724ꢀ728.
(52) Hehre, W. J.; Ditchfield, R.; Pople, J. A. J. Chem. Phys. 1972, 56, 2257ꢀ2261.
(53) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys. 2010, 132, 154104.
(54) Grimme, S. Chem. Eur. J. 2012, 18, 9955ꢀ9964.
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14
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18
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(55) Schäfer, A.; Horn, H.; Ahlrichs, R. J. Chem. Phys. 1992, 97, 2571ꢀ2577.
(56) Weigend, F.; Ahlrichs, R. Phys. Chem. Chem. Phys. 2005, 7, 3297ꢀ3305.
(57) Furche, F.; Ahlrichs, R. J. Chem. Phys. 2002, 117, 7433ꢀ7447.
(58) Circular Dichroism: Principles and Applications, 2nd Edition; Berova, N.; Nakanishi, K.;
Woody, R. W., Eds.; John Wiley & Sons: New York, 2000.
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Table of Contents Graphic:
4
*
R
R*
5
N
N
N
N
6
7
hν1
8
9
R*
R*
hν2
hν3
R*
R*
(
)
trans
cis- M
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N
N
cis-(P)
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