Light and chemically driven molecular machines showing a unidirectional four-state switching cycle

Article abstract of DOI:10.1021/acs.joc.5b00026

The imitation of macroscopic movements at the molecular level is a key step in the development of nanomachines. The challenge is the synthesis of molecules that are able to transform external stimuli into a direction-controlled mechanical movement. The more complex such motion sequences are, the more difficult is the construction of the corresponding nanomachine. Here, we present a system that demonstrates a unidirectional, four-state switching cycle that bears similar characteristics to the arm movements of a human breaststroke swimmer. Like the latter, the molecules have a torso and two arms. The arms consist of bipyridine units and can be folded and stretched by addition and removal of copper ions. The unidirectional rotation of the arms is achieved by light-induced switching of an azo unit.

Full text of DOI:10.1021/acs.joc.5b00026

Article
pubs.acs.org/joc
Light and Chemically Driven Molecular Machines Showing a
Unidirectional Four-State Switching Cycle
Gebhard Haberhauer,*,† Christoph Burkhart,† Sascha Woitschetzki,† and Christoph Wolper‡
̈
‡
†Institut fur Organische Chemie, Institut fur Anorganische Chemie, Universitat Duisburg-Essen, Universitatsstr. 7, D-45117 Essen,
Germany
̈
̈
̈
̈
S
* Supporting Information
ABSTRACT: The imitation of macroscopic movements at the
molecular level is a key step in the development of nanomachines.
The challenge is the synthesis of molecules that are able to
transform external stimuli into a direction-controlled mechanical
movement. The more complex such motion sequences are, the
more difficult is the construction of the corresponding nano-
machine. Here, we present a system that demonstrates a
unidirectional, four-state switching cycle that bears similar
characteristics to the arm movements of a human breaststroke
swimmer. Like the latter, the molecules have a torso and two arms.
The arms consist of bipyridine units and can be folded and
stretched by addition and removal of copper ions. The
unidirectional rotation of the arms is achieved by light-induced
switching of an azo unit.
is controlled by the chiral scaffold. The sequence of motion
shows, analogously to the arm movements of a human
breaststroke swimmer, four states that can be observed by
CD and UV spectroscopy.
INTRODUCTION
■
In recent years, a large variety of synthetic molecular machines
have been published.1 The design of artificial molecular
machines often takes inspiration from the macroscopic
world.2 Here, the aim and challenge are to construct a single
molecule that shows mechanical motion caused by external
stimulation resembling the movement of its macroscopic
pendant. These attempts have yielded analogues of rotors,3
gears,4 clutches,5 shuttles,6 ratchets,7 elevators,8 muscles,9 etc.10
Furthermore, several entirely synthetic molecular motors have
been designed to convert energy into a controlled rotary
motion.11 As stimuli, chemical energy,12 light energy,13
electron-transfer processes,14 or a combination of different
types of energy15 has been used.
A special challenge is the construction of molecular machines
showing unidirectional, multi-state switching cycles. The
problem in the design of such systems is that the path of
leaving the starting state must differ from the path returning
back to the starting point,16 as otherwise no mechanical work is
performed during one cycle. Therefore, a system is needed that,
on one hand, is flexible enough to allow a complex motion
sequence and, on the other hand, is so rigid that the
movements are controlled in a single direction.
RESULTS AND DISCUSSION
■
Structure, Concept, and Principle of the Molecular
Machine. The targeted unidirectional nanomachine should
pass through a cycle of four states. Such a cycle (I → II → III
→ IV → I), together with the structure, concept, and principle
of the nanomachine, is depicted in Figure 1. The system
consists of a scaffold, which must be chiral to control the
direction of motion, two arms, and two types of hinge (blue
and red circles in Figure 1). Staying with the comparison of this
system with the arm movements of a human breaststroke
swimmer, the scaffold corresponds to the human torso and the
arms represent human arms. The blue hinge corresponds to the
shoulder joints, and the red hinges represent the elbow joints.
In state I, both arms are stretched forward. During the
transition from state I to state II, a rotation of the stretched
arms around the blue hinge occurs. This motion can also be
considered to be the power stroke of a breaststroke swimmer. It
is of the utmost importance that this motion is directed
(unidirectional); this means that in our case the right arm in
Figure 1 must rotate only clockwise, whereas the left arm must
move counterclockwise. The second stroke is the folding of the
two arms around the two red hinges (II → III). In the third
Here, we present the design of two entirely synthetic
machines that demonstrate unidirectional, four-state switching
cycles that bear similar characteristics to the arm movements of
a human breaststroke swimmer. They are single organic
molecules having a size of about 2 nm and consisting of a
peptidic scaffold (torso) and two flexible arms. The arms can be
moved by external stimuli, and the direction of the movement
Received: January 6, 2015
Published: January 13, 2015
© 2015 American Chemical Society
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We intended to build the targeted nanomachine in two steps.
The first step was the development of a unidirectional switch
consisting of a chiral scaffold and a hinge that performs the
rotation of the arms unidirectionally (blue hinge in Figure 1). If
the direction of motion was successfully proved, then we
wanted to attach the two arms, with each possessing a further
hinge (red hinges in Figure 1), in a second step.
Synthesis and Functionality of the Unidirectional
Switch. For the synthesis of the unidirectional switch, we
combined a chiral imidazole-containing macrocycle with an
azobenzene unit. Imidazole-containing macrocycles17 based on
marine peptides18 have already been successfully used for the
synthesis of molecular machines in which the direction of
motion plays an important role.19−21 Azobenzenes are very
popular light-driven switching units due to their high
reversibility and high photostability, which offer a multitude
of switching cycles.22 Furthermore, they show a high-amplitude
change between the stretched trans form and the more compact
cis isomer, and the direction of movement is controllable.23,24
For our approach, it is important that the orientation of the
arms relative to each other can be controlled in both states.
That means that the arms are first stretched forward and that
after the switching process they should be turned by 90° and
point to the side. A system that meets these requirements is a
meta-substituted azobenzene unit attached to a chiral imidazole-
containing clamp.23b The synthesis of this system is depicted in
Figure 2a. The oxidative coupling of aniline 1 leads to 4-fold-
Figure 1. Structure, concept, and principle of the nanomachine. The
nanomachine consists of a torso and two arms. The arms can be
unidirectionally rotated around the blue hinge. The stretching/folding
of the two arms takes place around the two red hinges. Sequence of
motions: I → II (directed motion of the forward-stretched arms from
the front to the side; power stroke), II → III (folding of the arms), III
→ IV (rotation of the folded arms), and III → IV (stretching of the
arms).
stroke, a rotation of the folded arms around the blue hinge
takes places (III → IV) whereby the direction occurs in exactly
the inverse fashion as that in the first step. The fourth stroke is
the stretching of the arms, which leads back to starting state I
and completes the swimming cycle (IV → I).
Figure 2. (a) Synthesis of unidirectional switch 5. Reaction conditions: (i) MeOH, SOCl2, 96%; (ii) MnO2, toluene, 70 °C, 56%; (iii) LiAlH4,
dichloromethane, 0 °C, 96%; (iv) Ph3P, NBS, THF, 85%; (v) H2, Pd(OH)2/C, DCM/MeOH, 95%; (vi) Cs2CO3, 3, acetonitrile, Δ, 84%. (b)
Molecular structures of trans-5, cis-(P)-5, and cis-(M)-5 calculated by means of B3LYP/6-31G*.
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Figure 3. (a) CD spectrum of azo switch 5 before (blue) and after (red) irradiation (λ = 365 nm, 10 s; c = 1.0 × 10−4 M in DCM). (b) CD spectra
of trans-5 (blue), cis-(P)-5 (red) and cis-(M)-5 (green) calculated using TD-B3LYP/6-31G*. (c) UV spectrum of azo switch 5 before (blue) and
after (red) irradiation (λ = 365 nm, 10 s; c = 1.0 × 10−4 M in DCM). (d) UV spectra of trans-5 (blue), cis-(P)-5 (red), and cis-(M)-5 (green)
calculated using TD-B3LYP/6-31G*.
substituted azobenzene 2. Diester 2 can be transformed via two
steps into benzylic bromide 3, which was reacted with chiral
clamp 4b to the desired azo switch, 5. Chiral clamp 4b was
synthesized from commercially available clamp 4a by hydro-
genation.19
(Figures 3 and S3−S5). In the UV spectra, the switching
process can be observed by the decrease of the absorption band
at ca. 330 nm (Figure 3c). This change in the π → π* band is
typical for isomerization of azobenzene derivatives.22a The
experimentally measured CD spectrum of trans-5 matches quite
well with the simulated one (Figure 3). In the simulated CD
spectrum of cis-(M)-5, a positive Cotton effect of the n → π*
transition at values above 400 nm is found. For the cis-(P)
isomer, a negative Cotton effect of the n → π* transition is
predicted, which is consistent with the measured spectrum.
To investigate the motion during the switching process, the
structures of the three possible isomers, trans-5, cis-(P)-5, and
cis-(M)-5, were geometrically optimized by means of B3LYP/6-
31G* (Figure 2b). Subsequently, their CD and UV spectra
were simulated on the basis of time-dependent density
functional theory (TD-DFT) with the B3LYP functional and
by employing the 6-31G* basis set. In Figure 2b, the calculated
structures are depicted. It turned out that the cis-(P) form is
more stable by 83 kJ/mol than the cis-(M) isomer. This huge
energy difference is responsible for the unidirectionality of the
switching process: Starting from the trans isomer, only the
more stable cis-(P) isomer is formed during the switching
process. Furthermore, the orientation of the bromine atoms in
the isomers is ideal for using 5 to construct a molecular
machine imitating the mechanical motion sequence of the arms
of a human breaststroke swimmer. In the trans isomer, the
bromine arms point forward, whereas in the cis-(P) isomer, they
are turned by 90° and point to the right and left sides,
respectively. Furthermore, we managed to grow crystals of
trans-5, which were investigated by X-ray analysis. A
comparison shows that the DFT-calculated conformation of
the switching units matches well with the one found in the solid
state (Figures S1 and S2).
1
Furthermore, the obtained cross-peaks in the H−1H NOESY
NMR spectrum of cis-5 can be explained only if the formed cis
isomer adopts P configuration (Figure S4). Accordingly, the
light-induced switching process is indeed unidirectional, as
trans-5 is undoubtedly transformed only into cis-(P)-5. The
NMR spectra as well as the HPLC spectra confirm that only
one cis isomer is formed by irradiation with 365 nm light
(Figures S3 and S5). It is also apparent, however, that the
extent of the switching process is lower than usually observed
for azobenzene units. Only 20% of 5 is switched by irradiation
with 365 nm light (Figure S5). The reverse isomerization from
cis-(P)-5 to trans-5 is triggered by irradiation with 405 nm light
(Figure S3). The switching process is repeatable almost any
number of times without a noticeable change in the spectra.
Synthesis and Functionality of the Molecular Ma-
chines Imitating the Motion Sequence of a Breaststroke
Swimmer. On the basis of unidirectional switch 5, we
intended to design light and chemically driven nanomachines
by attaching additional arms whose shape is controlled by the
addition/removal of metal ions (cf. Figure 1). As arms, we
The unidirectionality of the switching process of 5 was
investigated using HPLC, NMR, CD, and UV spectroscopy
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Scheme 1. (a) Synthesis of Unidirectional Nanomachine 9 and (b) Motion Principle of the Bipyridine Arms of Nanoswimmer
a
9
a
(a) Reaction conditions: (i) 4-aminophenylboronic acid pinacol ester, Pd(PPh3)4, K2CO3, H2O/dioxane, Δ, 31%; (ii) 4-methoxyphenylboronic
acid, Pd(PPh3)4, K2CO3, H2O/dioxane, Δ, 66%; (iii) 4-chlorocarbonylbenzeneboronic anhydride, THF, 71%; (iv) trans-5, Pd(PPh3)4, K2CO3, H2O/
dioxane, 365 nm, Δ, 34%. (b) Complexation of the bipyridine units with Cu2+ causes the folding of the arms (right); the addition of cyclam leads
back to the opened arms (left).
a
Scheme 2. Synthesis of Unidirectional Nanomachine 12
a
Reaction conditions: (i) 4-methoxyphenylboronic acid, Pd(PPh3)4, K2CO3, H2O/dioxane, Δ, 71%; (ii) n-BuLi, ClSnBu3, tetrahydrofuran, −78 °C;
(iii) trans-5, Pd(PPh3)4, toluene, 365 nm, Δ, 49%.
decided to use 6,6′-substituted 2,2′-bipyridines, as they are
known to be completely and reversibly switchable (Scheme
1b).25 Because noncomplexed 2,2′-biypridine units have an N−
C−C−N dihedral angle of about 180°, the substituents in
positions 6 and 6′ point in different directions and the 2,2′-
biypridine arm is opened. The addition of salts containing
metal ions, for example, Cu2+, leads to a complexation that is
accompanied by rotation around the C−C bipyridine bond
axis.26 In the complex, the N−C−C−N dihedral angle is ca. 0°,
the substituents in position 6 and 6′ point into the same
direction (Scheme 1b), and the 2,2′-biypridine arm is folded.
The reversibility of this movement, the opening of the arms, is
achieved chemically by the addition of cyclam, which
complexes Cu2+ ions better than bipyridine units.20
For linking the arms with the chiral scaffold, we chose two
approaches: In the first nanomachine (9, Scheme 1), the
bipyridine unit is separated from the azobenzene by a rigid
spacer. Here, the additional rigid spacer should ensure that the
two switching systems are spatially separated from each other
to avoid hindrance during the switching process. In the second
nanomachine (12, Scheme 2), the bipyridine unit is directly
bound to the meta position of the azobenzene.
The synthesis of light and chemically driven nanomachine 9
is depicted in Scheme 1a and basically corresponds to a Suzuki
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Figure 4. CD (left) and UV spectra (right) of states I−IV of light and chemically driven switch 9 in dichloromethane/acetonitrile (90:10; c = 2.0 ×
10−5 M) at 20 °C. During a four-stroke swimming cycle, the states are progressed through in the following order: I (blue) → II (red) → III (orange)
→ IV (green) → I (violet). Transition from state I to state II is caused by irradiation with 365 nm light (10 s). Transition from state II to state III is
caused by the addition of 3.2 equiv of Cu2+. Transition from state III to state IV is caused by irradiation with 405 nm light (10 s). Transition from
state IV to state I is caused by the addition of 10 equiv of cyclam.
Figure 5. CD (left) and UV spectra (right) of states I−IV of light and chemically driven switch 12 in dichloromethane/acetonitrile (90:10; c = 2.0 ×
10−5 M) at 20 °C. During a four-stroke swimming cycle, the states are progressed through in the following order: I (blue) → II (red) → III (orange)
→ IV (green) → I (violet). Transition from state I to state II is caused by irradiation with 365 nm light (10 s). Transition from state II to state III is
caused by the addition of 2.4 equiv of Cu2+. Transition from state III to state IV is caused by irradiation with 405 nm light (10 s). Transition from
state IV to state I is caused by the addition of 44 equiv of cyclam.
coupling27 of two bipyridine arms with the unidirectional
switch, trans-5. The so-obtained nanomachine (trans-9) adopts
state I; this means that both arms are stretched forward (cf.
Figure 1). The synthesis of nanomachine 12 takes place
according to a similar principle (Scheme 2). Here, stannane 11,
which can be synthesized in two steps from 6,6′-dibromo-2,2′-
dipyridyl (6), is reacted with switch trans-5 using a Stille
coupling. The so-obtained nanomachine, 12, also adopts state I.
After successful nanomachine synthesis, we wanted to first
test if light-induced switching of the systems can still be
achieved. Therefore, we analyzed the two systems via HPLC,
NMR, CD, and UV spectroscopy (Figures S6−S11). In all
spectra, the switching process can be proven. In the UV spectra,
a decrease of the π → π* band at ca. 330 nm can be observed.
However, this effect is not very distinct for switch 9 (Figures S6
and S7). The unidirectionality of the process can be seen in the
NMR spectra: Only one of the two diastereomeric cis isomers is
found (Figures S8 and S9). The negative Cotton effects of the
n → π* transition at values above 400 nm can be ascribed to
the cis-(P) isomers (Figures S6 and S7). Accordingly,
irradiation with 365 nm light leads to the transition from
state I (trans-9/trans-12) to state II (cis-(P)-9/cis-(P)-12).
Furthermore, a comparison of systems 9 and 12 shows that
the extent of light-induced switching is different for the two
machines. In the case of switch 9, only ca. 20% is involved in
the switching process (Figures S8 and S10). However, in
system 12, ca. 30% of the azobenzene units are switched by
light (Figures S9 and S11). We ascribe this to the fact that in
the case of 9 a part of the irradiated light is absorbed by the
rigid spacers so that less light is available for excitation of the
azobenzene unit.
Irradiation with 405 nm light returns state II to initial state I
(trans-9/trans-12). This switching processes are repeatable
almost any number of times without a noticeable change in the
spectra.
In the second step, we wanted to test if the bipyridine units
of nanomachines 9 and 12 can also be switched. Therefore, the
nanomachines were titrated with different metal ions in DCM/
MeCN and analyzed by CD and UV spectroscopy. Addition-
ally, the metal complexes were investigated by mass
spectrometry. Here, complete conversion was achieved only
with copper ions, and the corresponding metal complexes were
detected by ESI+. In the UV spectra, the formation of copper−
bipyridine complexes can be easily observed by means of an
increase of the absorption band at ca. 370 nm and a decrease of
the band at 320 nm (Figures S12 and S13). For switch 9,
complete conversion is reached at 3.15 equiv; for switch 12,
only 2.15 equiv is necessary.
Even in the CD spectra, the formation of copper complexes
can be observed. As expected, the bipyridine complex units in
switch 12, which are closer to the chiral clamp, show more
distinct changes in the Cotton effects (Figures S12 and S13).
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After titration, the solutions were examined by mass
spectrometry. In addition to the dinuclear complexes
(9*Cu22+, 12*Cu22+), the mononuclear complexes (9*Cu2+,
12*Cu2+) can be unambiguously proven. The addition of the
strong copper ion binder cyclam leads to the original (not
complexed) compounds (Figures S12 and S13). Thus,
titrations with Cu2+ ions and cyclam show that the bipyridine
arms can be folded (trans-9*Cu24+; state IV) and reopened
(state I, trans-9), as expected (Figures S12 and S13).
EXPERIMENTAL SECTION
■
Computational Study. All calculations were performed by using
the program package Gaussian 09.28 The geometrical parameters of
trans-5, cis-(P)-5, and cis-(M)-5 were optimized without symmetry
restriction by means of density functional theory (DFT). For the DFT
method, we used the B3LYP29−31 functional and the 6-31G*32 basis
set. Frequency calculation revealed that the optimized structures have
no imaginary frequency.
The CD and UV spectra of trans-5, cis-(P)-5, and cis-(M)-5 were
simulated with time-dependent density functional theory (TD-
DFT),33 using the B3LYP functional and the 6-31G* basis set. TD-
DFT calculations were performed at the optimized ground-state
geometry (B3LYP/6-31G*) of the compounds. The energy, oscillator
strength, and rotatory strength were calculated for each of the 200
lowest singlet excitations.
The combination of both switches using the different stimuli
subsequently allows several cycles to be performed for light and
chemically driven switches 9 and 12. The UV and CD spectra
for the first cycle are depicted in Figures 4 and 5. The starting
point is the trans isomers (state I), which are transformed in the
first stroke into state II (cis-(P) isomers) by irradiation with
365 nm light. This switching process is observable by the
decrease of the absorption bands at 330 nm in the UV spectra
and the more negative Cotton effect at 420 nm. During the
second stroke, the addition of Cu2+ ions causes the folding of
the arms (copper complexes of the cis-(P) isomers), which
corresponds to state III. In the UV spectra, this process can be
observed by means of the bathochromic shifts of the bipyridine
bands to 380 nm. Rotation of the folded arms is triggered by
irradiation with 405 nm light, and state IV (copper complexes
of the trans isomers) is formed in the third stroke. This
reisomerization becomes noticeable by an increase of the
absorption band at 330 nm in the UV spectra. The so-recorded
spectra are consistent with the ones obtained by titration of the
trans isomers with Cu2+ (Figures S12 and S13). Addition of
cyclam leads to the stretching of the arms, resulting in the trans
isomers, which correspond to state I. The fourth stroke
completes the cycle. The spectra are again identical with those
of the starting compounds; this makes the case for the existence
of a reversible cycle. The cycle can be repeated several times.
The number of cycles is not limited by the system but by the
measurement technique: With increasing overall concentration
of all of the components, the absorption of the entire system is
too high to obtain meaningful CD signals in the desired part of
the spectra.
General Remarks. All chemicals were reagent grade and were used
as purchased. Reactions were monitored by TLC analysis with silica
gel 60 F254 thin-layer plates. Flash chromatography was carried out on
1
silica gel 60 (230−400 mesh). H, 13C, and 2D NMR spectra were
recorded on 300, 500, and 600 MHz spectrometers. All chemical shifts
(δ) are given in ppm. The spectra were referenced to the peak for the
protium impurity in the deuterated solvents indicated in brackets in
the analytical data. HRMS spectra were recorded using a time-of-flight
(TOF) detector. Two high-power light-emitting diodes (LEDs) were
used for the light-induced switching processes. The first light source
irradiates 365 nm light, and the second one, 405 nm. Chiral clamp 4a
was purchased from Squarix GmbH.
Synthesis of Methyl 3-Amino-5-bromobenzoate (13). Aniline
1 (718 mg, 3.30 mmol) was dissolved in methanol and cooled to 0 °C.
SOCl2 (4.8 mL, 66.7 mmol) was added dropwise to the solution, and
the mixture was allowed to reach room temperature overnight. The
volatiles were removed in vacuo, and the remaining solid was dissolved
in water. A saturated solution of NaHCO3 was added until a pH of 7
was reached. The aqueous solution was extracted several times with
ethyl acetate. The combined organic phases were dried over MgSO4
and concentrated in vacuo to give 13 (730 mg, 3.17 mmol, 96%) as a
grayish solid. mp 97−98 °C. 1H NMR (500 MHz, CDCl3): δ 7.52 (dd,
4JH,H = 1.4 Hz, 4JH,H = 1.4 Hz, 1 H, Har), 7.25 (dd, 4JH,H = 1.4 Hz, 4JH,H
= 2.2 Hz, 1 H, Har), 6.99 (dd, 4JH,H = 2.0 Hz, 4JH,H = 2.0 Hz, 1 H, Har),
3.89 (s, 3 H, CH3), 3.83 (bs, 2 H, NH2) ppm. 13C NMR (125 MHz,
CDCl3): δ 166.0, 147.7, 132.6, 122.9, 122.3, 121.6, 114.6, 52.3 ppm.
HRMS (ESI+) [C8H879BrNO2 + Na]+ calcd, 251.9636; found,
251.9624. IR (ATR): 3410, 3329, 3220, 3095, 2953, 1708, 1636,
1601, 1467, 1444, 1430, 1308, 1273, 1242, 1187, 1089, 1003, 914, 896,
853, 833, 768, 729, 669 cm−1. UV/vis (DCM): λmax (log ε) = 324
(3.49) nm.
CONCLUSIONS
■
Synthesis of 2. Aniline 13 (1.52 g, 6.60 mmol) was dissolved in
toluene (25 mL), and MnO2 (13.2 mmol, 1.15 g) was added. The
reaction mixture was warmed to 70 °C and stirred in the dark for
several days at that temperature. Afterward, the reaction mixture was
filtered over Celite, and the solvent was removed in vacuo. Column
chromatography of the residue on silica gel (dichloromethane) led to
diester 2 (436 mg, 29%) as an orange solid and to starting material 13
We have shown that we were able to design molecular
machines that demonstrate unidirectional, four-state switching
cycles that bear similar characteristics to the arm movements of
a human breaststroke swimmer. They are based on a peptidic,
macrocyclic scaffold that controls the direction of motion. The
arms performing the swimming movements are rotated around
one hinge and are stretched and folded by another hinge. The
first hinge is a meta-substituted azobenzene attached to the
chiral scaffold and can be switched by light. The arms are
bipyridine units that are either directly attached or connected
via rigid spacers to the azobenzene unit. The bipyridine units
are stimulated by Cu2+ ions. The movements of these machines
are triggered by alternating addition of chemicals and
irradiation with light. The limiting factor for the repeatability
of the cycles is the dilution effect caused by the addition of
solutions, which worsens the recording of the spectra. The rate-
limiting factor is the time to record the spectra for each cycle.
The current work is a promising small step to an artificial
nanoswimmer that is propelled in solution by an external
stimuli.
1
(841 mg, 1.84 mmol, 56%). mp 175−176 °C. H NMR (500 MHz,
4
4
CDCl3) trans isomer: δ 8.53 (dd, JH,H = 1.6 Hz, JH,H = 1.6 Hz, 2 H,
Har), 8.31 (dd, 4JH,H = 1.7 Hz, 4JH,H = 1.7 Hz, 2 H, Har), 8.23 (dd, 4JH,H
= 1.8 Hz, 4JH,H = 1.8 Hz, 2 H, Har), 3.99 (s, 6 H, CH3) ppm; cis isomer:
δ 8.00 (dd, 4JH,H = 1.7 Hz, 4JH,H = 1.7 Hz, 2 H, Har), 7.39 (dd, 4JH,H
=
1.6 Hz, 4JH,H = 1.6 Hz, 2 H, Har), 7.19 (dd, 4JH,H = 1.8 Hz, 4JH,H = 1.8
Hz, 2 H), Har, 3.89 (s, 6 H, CH3) ppm. 13C NMR (125 MHz, CDCl3):
δ 165.0, 152.8, 135.1, 132.9, 128.9, 124.2, 123.2, 52.7 ppm. HRMS
(ESI+) [C16H1279Br81BrN2O4 + Na]+ calcd, 478.9041; found,
478.9029. IR (ATR): 3444, 3074, 3035, 2964, 2850, 1841, 1793,
1732, 1563, 1446, 1432, 1280, 1242, 1203, 1183, 1103, 995, 922, 907,
887, 836, 763, 730, 683 cm−1. UV/vis (DCM): λmax (log ε) = 318
(4.21), 444 (2.73) nm.
Synthesis of 3,3′-Dibromo-5,5′-di(hydroxymethyl)-
azobenzene (14). A solution of LiAlH4 in THF (2 M, 0.36 mL,
0.75 mmol) was added to 2 (56 mg, 0.12 mmol) in anhydrous
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dichloromethane at 0 °C under argon, and the mixture was stirred for
3 h at 0 °C. Then, dichloromethane (20 mL) and water (1.0 mL) were
added to the reaction mixture. The organic layer was separated, and
the aqueous solution was extracted several times with dichloro-
methane. The combined organic phases were dried over MgSO4 and
concentrated in vacuo to yield diol 14 (96%, 46 mg, 0.11 mmol) as an
orange solid, which was used for the next step without further
was removed, and the crude product was purified by column
chromatography over silica gel (n-hexane/ethyl acetate, 1:1) to give
1
7 (301 mg, 0.92 mmol, 31%) as a white solid. mp 120−121 °C. H
NMR (600 MHz, CDCl3): δ 8.58 (dd, 4JH,H = 0.7 Hz, 3JH,H = 7.8 Hz, 1
4
3
H, Har), 8.26 (dd, JH,H = 0.8 Hz, JH,H = 7.8 Hz, 1 H, Har), 7.97 (d,
3JH,H = 8.9 Hz, 2 H, Har), 7.81 (t, 3JH,H = 8.0 Hz, 1 H, Har), 7.68 (m, 2
4
3
H, Har), 7.48 (dd, JH,H = 0.8 Hz, JH,H = 8.1 Hz, 1 H, Har), 6.79 (d,
3JH,H = 8.9 Hz, 2 H, Har), 3.85 (s, 2 H, NH2) ppm. 13C NMR (151
1
purification. mp 186−188 °C. H NMR (500 MHz, CD3OD) trans
isomer: δ 7.92 (m, 2 H, Har), 7.90 (m, 2 H, Har), 7.70 (m, 2 H, Har),
4.71 (s, 4 H, CH2) ppm; cis isomer: δ 7.37 (m, 2 H, Har), 6.90 (m, 2 H,
Har), 6.84 (m, 2 H, Har), 4.50 (s, 4 H, CH2). 13C NMR (125 MHz,
CD3OD): δ 154.7, 147.0, 133.4, 124.4, 124.1, 122.2, 63.9 ppm. HRMS
(ESI+) [C14H1279Br81BrN2O2 + Na]+ calcd, 422.9143; found,
422.9149. IR (ATR): 3305, 3082, 2922, 2855, 1659, 1602, 1575,
1450, 1434, 1358, 1307, 1253, 1218, 1132, 1097, 1020, 987, 903, 854,
821, 733, 685 cm−1. UV/vis (DCM): λmax (log ε) = 323 (4.19), 442
(2.79) nm.
MHz, CDCl3): δ 157.8, 156.5, 153.7, 147.6, 141.4, 139.1, 137.5, 129.5,
128.1, 127.7, 119.8, 119.6, 118.6, 115.0 ppm. HRMS (ESI+)
[C16H1279BrN3 + Na]+ calcd, 348.0112; found, 348.0105. IR (ATR):
3427, 3411, 3300, 3199, 1641, 1606, 1591, 1572, 1547, 1519, 1459,
1448, 1426, 1415, 1373, 1344, 1320, 1285, 1273, 1227, 1185, 1168,
1147, 1124, 1108, 1092, 1070, 1048, 1012, 983, 960, 929, 904, 853,
836, 816, 808, 784, 720, 680, 657 cm−1. UV/vis (DCM): λmax (log ε) =
299 (4.43) nm.
Synthesis of 4-(6′-(4-Methoxyphenyl)-[2,2′-bipyridin]-6-yl)-
aniline (15). 4-Methoxyphenylboronic acid (152 mg, 1.00 mmol) was
dissolved in dioxane (7.0 mL) under an argon atmosphere. Pd(PPh3)4
(5.0 mg, 0.004 mmol), an aqueous solution of potassium carbonate
(saturated; 0.7 mL), and bromide 7 (150 mg, 0.46 mmol) were added
to the solution. The reaction mixture was warmed to 80 °C and stirred
at that temperature overnight. After cooling to room temperature,
dichloromethane (60 mL) and water (10 mL) were added. The phases
were separated, and the aqueous layer was extracted several times with
dichloromethane. The organic layers were combined and dried over
MgSO4, the solvent was removed, and the crude product was purified
by column chromatography over silica gel (n-hexane/ethyl acetate,
1:1) to give 15 (107 mg, 0.30 mmol, 66%) as a white solid. mp 246−
247 °C. 1H NMR (600 MHz, CDCl3): δ 8.53 (d, 3JH,H = 7.7 Hz, 1 H,
Synthesis of 3. Triphenylphosphine (231 mg, 0.88 mmol) and N-
bromosuccinimide (157 mg, 0.88 mmol) were added to a solution of
diol 14 (92 mg, 0.23 mmol) in tetrahydrofuran at 0 °C under an argon
atmosphere. The mixture was allowed to reach room temperature
overnight. The volatiles were removed in vacuo, and the remaining
solid was subjected to column chromatography (silica gel, n-hexane/
dichloromethane, 10:2) to afford 3 (103 mg, 0.20 mmol, 85%) as an
1
orange solid. mp 185−187 °C. H NMR (500 MHz, CDCl3) trans
isomer: δ 7.99 (m, 2 H, Har), 7.91 (m, 2 H, Har), 7.68 (m, 2 H, Har),
4.52 (s, 4 H, CH2) ppm; cis isomer: δ 7.35 (m, 2 H, Har), 7.01 (m, 2 H,
Har), 6.69 (m, 2 H, Har), 4.28 (s, 4 H, CH2) ppm. 13C NMR (125
MHz, CDCl3): δ 153.1, 140.7, 134.6, 125.1, 123.4, 123.3, 31.2 ppm.
HRMS (ESI−) [C14H1079Br281Br2N2 + 81Br]− calcd, 606.6700; found,
606.6656. IR (ATR): 3124, 3089, 3055, 3027, 2973, 2923, 2859, 1799,
1779, 1598, 1557, 1429, 1306, 1268, 1241, 1209, 1140, 1121, 1089,
996, 979, 908, 880, 823, 689, 660 cm−1. UV/vis (DCM): λmax (log ε) =
324 (4.28), 446 (2.74) nm.
3
3
Har), 8.49 (d, JH,H = 7.3 Hz, 1 H, Har), 8.13 (d, JH,H = 8.8 Hz, 2 H,
3
Har), 8.02 (d, JH,H = 8.5 Hz, 2 H, Har), 7.85 (m, 2 H, Har), 7.71 (dd,
4JH,H = 0.7 Hz, 3JH,H = 7.8 Hz, 1 H, Har), 7.68 (dd, 4JH,H = 0.7 Hz, 3JH,H
= 7.8 Hz, 1 H, Har), 7.04 (d, 3JH,H = 8.8 Hz, 2 H, Har), 6.81 (d, 3JH,H
=
8.6 Hz, 2 H, Har), 3.89 (s, 3 H, CH3), 3.84 (s, 2 H, NH2) ppm. 13C
NMR (151 MHz, CDCl3): δ 160.5, 156.3, 156.0, 155.9, 155.7, 147.4,
137.4, 137.3, 132.2, 129.9, 128.2, 128.1, 119.4, 119.0, 118.8, 118.3,
115.1, 114.1, 55.4 ppm. HRMS (ESI+) [C23H19N3O + Na]+ calcd,
376.1426; found, 376.1430. IR (ATR): 3459, 3371, 3215, 3000, 2962,
2932, 2907, 2837, 1602, 1561, 1512, 1457, 1433, 1373, 1300, 1286,
1266, 1244, 1178, 1157, 1129, 1115, 1086, 1026, 987, 963, 908, 841,
819, 792, 742 cm−1. UV/vis (DCM): λmax (log ε) = 294 (4.57) nm.
Synthesis of 8. 4-Chlorocarbonylbenzeneboronic anhydride (90%,
61 mg, 0.33 mmol) was dissolved in tetrahydrofuran (8 mL) under an
argon atmosphere. Aniline 15 (67 mg, 0.19 mmol) dissolved in
tetrahydrofuran (5 mL) was added dropwise at room temperature.
Pyridine (0.08 mL) was added dropwise at room temperature, and the
resulting mixture was stirred overnight. The precipitate was separated
by filtration and air-dried to yield 8 (68 mg, 0.14 mmol, 71%) as a
Synthesis of trans-5. Cesium carbonate (326 mg, 1.00 mmol) was
added to a solution of clamp 4b (25 mg, 0.045 mmol) and dibromide
3 (42 mg, 0.080 mmol) in anhydrous acetonitrile (25 mL), and the
mixture was refluxed at 90 °C for 4 h under an argon atmosphere.
After cooling to room temperature, dichloromethane (60 mL) and
water (15 mL) were added. The organic layer was washed with water,
dried over MgSO4, and concentrated in vacuo. Column chromatog-
raphy of the residue on silica gel (dichloromethane/ethyl acetate/
methanol, 75:25:1) provided compound trans-5 (35 mg, 0.038 mmol,
84%) as an orange solid. mp > 350 °C. 1H NMR (600 MHz, CDCl3):
3
δ 7.90 (s, 2 H, Har), 7.52 (s, 2 H, Har), 7.42 (d, JH,H = 10.5 Hz, 2 H,
3
NH), 7.12 (d, JH,H = 5.9 Hz, 2 H, NH), 5.90 (s, 2 H, Har), 5.36 (d,
2JH,H = 17.4 Hz, 2 H, CH2), 4.98 (d, 2JH,H = 17.5 Hz, 2 H, CH2), 4.97
3
3
(m, 2 H, CH), 4.61 (dd, JH,H = 8.0 Hz, JH,H = 10.5 Hz, 2 H, CH),
2.53−2.48 (m, 2 H, CH), 2.31−2.25 (m, 2 H, CH), 2.18 (s, 6 H,
CH3), 1.16 (d, 3JH,H = 6.7 Hz, 6 H, CH3), 1.15 (d, 3JH,H = 6.7 Hz, 6 H,
CH3), 0.93 (d, 3JH,H = 6.2 Hz, 6 H, CH3), 0.92 (d, 3JH,H = 6.6 Hz, 6 H,
CH3) ppm. 13C NMR (151 MHz, CDCl3): δ 171.1, 162.4, 153.0,
145.9, 138.7, 134.7, 131.2, 130.6, 125.7, 123.5, 117.9, 59.2, 51.3, 46.5,
33.0, 31.4, 19.6, 19.0, 18.5, 17.5, 10.1 ppm. HRMS (ESI+)
[C42H5279Br81BrN10O4 + Na]+ calcd, 943.2417; found, 943.2419. IR
(ATR): 3389, 3073, 2963, 2930, 2873, 2358, 1660, 1593, 1504, 1463,
1428, 1388, 1371, 1333, 1256, 1223, 1140, 1091, 1048, 1029, 991, 952,
881, 858, 819, 765, 731, 688 cm−1. UV/vis (DCM): λmax (log ε) = 324
(4.30), 445 (2.69) nm. CD (DCM): λmax (Δε) = 251 (−34.89), 273
(−0.85), 297 (−2.87), 343 (+1.79), 452 (−5.81 M−1 cm−1) nm.
Synthesis of 7. 4-Aminophenylboronic acid pinacol ester (646 mg,
2.95 mmol) was dissolved in dioxane (10.0 mL) under an argon
atmosphere. Pd(PPh3)4 (23 mg, 0.020 mmol), an aqueous solution of
potassium carbonate (saturated; 1.0 mL), and 6,6′-dibromo-2,2′-
dipyridyl (6) (926 mg, 2.95 mmol) were added to the solution. The
reaction mixture was warmed to 80 °C and stirred at that temperature
overnight. After cooling to room temperature, dichloromethane (60
mL) and water (10 mL) were added. The phases were separated, and
the aqueous layer was extracted several times with dichloromethane.
The organic layers were combined and dried over MgSO4, the solvent
1
white solid. mp > 250 °C. H NMR (600 MHz, DMSO-d6): δ 10.43
3
(s, 1 H, NH), 8.51 (m, 2 H, Har), 8.29 (d, JH,H = 8.2 Hz, 2 H, Har),
8.23 (d, 3JH,H = 8.8 Hz, 2 H, Har), 8.07−8.03 (m, 3 H, Har), 8.00−7.99
3
(m, 3 H, Har), 7.97−7.94 (m, 4 H, Har), 7.11 (d, JH,H = 8.9 Hz, 2 H,
Har), 3.85 (s, 3 H, CH3) ppm. 13C NMR (151 MHz, DMSO-d6): δ
165.7, 160.2, 155.1, 155.0, 154.9, 154.8, 140.2, 138.3, 138.2, 136.0,
133.9, 133.5, 130.9, 127.9, 126.9, 126.5, 120.2, 119.8, 119.6, 118.7,
118.5, 114.1, 55.2 ppm. HRMS (ESI+) [C30H24BN3O4 + Na]+ calcd,
524.1758; found, 524.1752. IR (ATR): 3280, 1639, 1607, 1589, 1564,
1528, 1513, 1468, 1436, 1396, 1355, 1328, 1299, 1274, 1173, 1135,
1114, 1083, 1027, 1012, 914, 843, 813, 788, 754, 742, 699, 670 cm−1.
UV/vis (MeOH): λmax (log ε) = 292 (4.73), 319 (4.65) nm.
Synthesis of trans-9. Boronic acid 8 (60 mg, 0.12 mmol) was
dissolved in dioxane (4.0 mL) under an argon atmosphere. Pd(PPh3)4
(1.0 mg, 0.001 mmol), an aqueous solution of potassium carbonate
(saturated; 0.4 mL), and azo compound trans-5 (22 mg, 0.024 mmol)
were added to the solution. The reaction mixture was stirred under an
argon atmosphere for 1 day at 80 °C under simultaneous irradiation
with UV light (λ = 365 nm). After cooling to room temperature,
dichloromethane (60 mL) and water (10 mL) were added. The phases
were separated, and the aqueous layer was extracted several times with
1893
DOI: 10.1021/acs.joc.5b00026
J. Org. Chem. 2015, 80, 1887−1895

The Journal of Organic Chemistry
Article
3
dichloromethane. The organic layers were combined and dried over
MgSO4, the solvent was removed, and the crude product was purified
by column chromatography over silica gel (dichloromethane/ethyl
acetate, 75:25) to provide trans-9 (13.7 mg, 0.008 mmol, 34%) as an
orange solid. mp > 350 °C. 1H NMR (600 MHz, CDCl3): δ 8.58 (dd,
4JH,H = 0.7 Hz, 3JH,H = 7.8 Hz, 2 H, Har), 8.55 (dd, 4JH,H = 0.7 Hz, 3JH,H
6 H, CH2), 0.90 (t, JH,H = 7.4 Hz, 9 H, CH3) ppm. HRMS (ESI+)
[C29H40N2O120Sn + H]+ calcd, 553.2241; found, 553.2246.
Synthesis of trans-12. Pd(PPh3)4 (3.0 mg, 0.002 mmol) was
added to a toluene solution (8 mL) of a mixture of azo compound
trans-5 (25 mg, 0.027 mmol) and stannane 11 (83 mg, 0.150 mmol)
under an argon atmosphere. The reaction mixture was stirred under
argon for 4 days at 95 °C by simultaneous irradiation with UV light (λ
= 365 nm). After cooling to room temperature, the mixture was
evaporated to dryness under reduced pressure. Column chromatog-
raphy of the residue on silica gel (dichloromethane/ethyl acetate/
methanol, 75:25:6) provided trans-12 (17.0 mg, 0.013 mmol, 49%) as
an orange solid. mp > 350 °C. 1H NMR (600 MHz, CDCl3/CD3OD):
δ 8.54 (d, 3JH,H = 7.9 Hz, 2 H, Har), 8.46 (d, 3JH,H = 7.7 Hz, 2 H, Har),
8.43 (s, 2 H, Har), 8.26 (s, 2 H, Har), 8.03 (d, 3JH,H = 8.8 Hz, 4 H, Har),
7.94 (d, 3JH,H = 10.7 Hz, 2 H, NH), 7.91 (t, 3JH,H = 7.8 Hz, 2 H, Har),
= 7.8 Hz, 2 H, Har), 8.24 (d, 3JH,H = 8.7 Hz, 4 H, Har), 8.14 (d, 3JH,H
8.8 Hz, 4 H, Har), 8.11 (s, 2 H, Har), 8.04 (m, 6 H, Har), 7.92−7.86 (m,
=
4
3
8 H, Har), 7.81−7.78 (m, 6 H, Har), 7.73 (dd, JH,H = 0.7 Hz, JH,H
=
3
7.8 Hz, 2 H, Har), 7.62 (s, 2 H, Har), 7.49 (d, JH,H = 10.6 Hz, 2 H,
NH), 7.21 (d, 3JH,H = 5.9 Hz, 2 H, NH), 7.05 (d, 3JH,H = 8.9 Hz, 4 H,
Har), 6.03 (s, 2 H, NH), 5.48 (d, 2JH,H = 17.2 Hz, 2 H, CH2), 5.11 (d,
2JH,H = 17.3 Hz, 2 H, CH2), 5.05 (dd, 3JH,H = 3.9 Hz, 3JH,H = 5.8 Hz, 2
H, CH), 4.66 (dd, 3JH,H = 7.8 Hz, 3JH,H = 10.5 Hz, 2 H, CH), 3.90 (s, 6
H, CH3), 2.58−2.52 (m, 2 H, CH), 2.35−2.29 (m, 2 H, CH), 2.25 (s,
6 H, CH3), 1.19 (d, 3JH,H = 6.7 Hz, 6 H, CH3), 1.18 (d, 3JH,H = 6.7 Hz,
6 H, CH3), 0.96 (d, 3JH,H = 8.5 Hz, 6 H, CH3), 0.94 (d, 3JH,H = 7.0 Hz,
6 H, CH3) ppm. 13C NMR (151 MHz, CDCl3): δ 171.2, 165.1, 162.6,
160.5, 156.06, 156.03, 155.77, 155.51, 153.1, 145.9, 143.1, 141.8,
138.7, 137.69, 137.60, 137.53, 135.7, 134.9, 134.3, 132.1, 130.5, 128.2,
127.9, 127.73, 127.68, 126.9, 121.2, 120.2, 119.8, 119.6, 119.4, 118.8,
118.7, 114.1, 59.3, 55.4, 51.4, 47.1, 33.0, 31.4, 19.7, 19.0, 18.6, 17.5,
10.2 ppm. HRMS (ESI+) [C102H96N16O8 + Na]+ calcd, 1695.7495;
found, 1695.7505. IR (ATR): 3384, 2962, 2927, 2872, 1667, 1597,
1564, 1514, 1463, 1434, 1402, 1390, 1372, 1317, 1302, 1248, 1178,
1152, 1104, 1085, 1043, 1028, 988, 953, 897, 847, 823, 796, 763, 743,
697, 667 cm−1. UV/vis (DCM/CH3CN, 9:1): λmax (log ε) = 297
(4.90), 320 (4.90), 426 (2.94) nm. CD (DCM/CH3CN, 9:1): λmax
(Δε) = 252 (−27.34), 332 (+9.78), 444 (−7.60 M−1 cm−1) nm.
Synthesis of 10. 4-Methoxyphenylboronic acid (330 mg, 2.17
mmol) was dissolved in dioxane (10.0 mL) under an argon
atmosphere. Pd(PPh3)4 (23 mg, 0.020 mmol), an aqueous solution
of potassium carbonate (saturated; 1.0 mL), and 6,6′-dibromo-2,2′-
dipyridyl (6) (1.025 g, 3.26 mmol) were added to the solution. The
reaction mixture was warmed to 80 °C and stirred at that temperature
overnight. After cooling to room temperature, dichloromethane (60
mL) and water (10 mL) were added. The phases were separated, and
the aqueous layer was extracted several times with dichloromethane.
The organic layers were combined and dried over MgSO4, the solvent
was removed, and the crude product was purified by column
chromatography over silica gel (n-hexane/ethyl acetate, 10:1) to give
7.84 (m, 4 H, Har), 7.67 (d, 3JH,H = 7.4 Hz, 2 H, Har), 7.43 (d, 3JH,H
7.2 Hz, 2 H, NH), 6.96 (d, 3JH,H = 8.8 Hz, 4 H, Har), 6.04 (s, 2 H, Har),
=
2
2
5.50 (d, JH,H = 17.2 Hz, 2 H, CH2), 5.17 (d, JH,H = 17.2 Hz, 2 H,
CH2), 5.01 (d, 3JH,H = 4.0 Hz, 2 H, CH), 4.44 (d, 3JH,H = 9.4 Hz, 2 H,
CH), 3.80 (s, 6 H, CH3), 2.35−2.30 (m, 2 H, CH), 2.17−2.10 (m, 2
H, CH), 2.16 (s, 6 H, CH3), 1.08 (d, 3JH,H = 6.5 Hz, 6 H, CH3), 1.07
(d, 3JH,H = 6.5 Hz, 6 H, CH3), 0.91 (d, 3JH,H = 7.0 Hz, 6 H, CH3), 0.89
(d, JH,H = 7.0 Hz, 6 H, CH3) ppm. 13C NMR (151 MHz, CDCl3/
3
CD3OD): δ 171.6, 163.0, 160.4, 156.2, 156.1, 155.3, 154.5, 152.9,
145.9, 141.0, 137.84, 137.54, 137.45, 135.1, 131.8, 130.1, 128.1, 126.8,
120.51, 120.46, 120.3, 119.7, 118.99, 118.85, 113.9, 59.8, 55.2, 50.9,
47.1, 33.5, 31.4, 19.3, 19.2, 18.0, 17.7, 9.9 ppm. HRMS (ESI+)
[C76H78N14O6 + Na]+ calcd, 1305.6127; found, 1305.6135. IR (ATR):
3305, 2955, 2921, 2852, 1737, 1660, 1606, 1564, 1514, 1462, 1430,
1374, 1337, 1301, 1251, 1174, 1090, 1056, 1027, 843, 799, 743, 720
cm−1. UV/vis (DCM): λmax (log ε) = 278 (4.61), 425 (2.89) nm. CD
(DCM): λmax (Δε) = 253 (−19.35), 279 (+2.61), 314−2.34), 448
(−5.94 M−1 cm−1) nm.
ASSOCIATED CONTENT
* Supporting Information
Molecular structures of cis-(P)-5, cis-(M)-5, and trans-5; CD,
■
S
HPLC, NMR and UV spectra; Cartesian coordinates and
1
absolute energies of cis-(P)-5, cis-(M)-5, and trans-5; H and
13C NMR spectra of the new compounds; crystal structure data
of trans-5; complete ref 28; and CIF file for trans-5. This
material is available free of charge via the Internet at http://
pubs.acs.org.
1
10 (526 mg, 1.54 mmol, 71%) as a white solid. mp 128−129 °C. H
3
NMR (600 MHz, CDCl3): δ 8.59 (d, JH,H = 7.2 Hz, 1 H, Har), 8.31
(d, 3JH,H = 7.8 Hz, 1 H, Har), 8.09 (d, 3JH,H = 8.9 Hz, 2 H, Har), 7.84 (t,
3
3JH,H = 7.8 Hz, 1 H, Har), 7.72 (d, JH,H = 7.8 Hz, 1 H, Har), 7.69 (t,
3
3JH,H = 7.8 Hz, 1 H, Har), 7.49 (d, JH,H = 7.8 Hz, 1 H, Har), 7.03 (d,
AUTHOR INFORMATION
Corresponding Author
*E-mail: gebhard.haberhauer@uni-due.de.
■
3JH,H = 8.9 Hz, 2 H, Har), 3.89 (s, 3 H, CH3) ppm. 13C NMR (151
MHz, CDCl3): δ 160.6, 157.7, 156.2, 153.9, 141.5, 139.1, 137.7, 131.8,
128.2, 127.9, 120.1, 119.9, 119.0, 114.1, 55.4 ppm. HRMS (ESI+)
[C17H1379BrN2O + Na]+ calcd, 363.0109; found, 363.0094. IR (ATR):
3087, 3040, 3006, 2971, 2933, 2838, 1608, 1572, 1548, 1516, 1462,
1422, 1375, 1325, 1301, 1278, 1249, 1180, 1165, 1152, 1128, 1116,
1068, 1032, 985, 957, 904, 835, 821, 784, 739, 718, 657 cm−1. UV/vis
(DCM): λmax (log ε) = 284 (4.37) nm.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was generously supported by the Deutsche
Forschungsgemeinschaft (DFG). A special thanks goes to
Dieter Blaser, Dr. Silvia Ernst, Helma Kallweit, and Petra
Schneider for helpful support.
■
Synthesis of 11. To a solution of bromide 10 (177 mg, 0.52
mmol) in dry tetrahydrofuran (8.0 mL) was added a solution of n-
butyllithium in hexane (0.30 mL, 2.5 M, 0.75 mmol) dropwise under
argon at −78 °C. The resulting mixture was stirred for 1 h before
adding ClSnBu3 (0.27 mL, 1.00 mmol) at −78 °C. The solution was
stirred at this temperature for 45 min and subsequently quenched with
a saturated solution of NH4Cl. After phase separation, the aqueous
phase was extracted with dichloromethane. The combined organic
layers were dried over MgSO4 and concentrated in vacuo to yield
stannane 11 (280 mg, 0.51 mmol, 98%) as a yellowish oil, which was
̈
REFERENCES
■
(1) (a) Molecular Switches, 2nd ed.; Feringa, B. L., Browne, W. R.,
Eds.; Wiley-VCH: Weinheim, Germany, 2011; Vol. 1. (b) Molecular
Switches, 2nd ed.; Feringa, B. L., Browne, W. R., Eds.; Wiley-VCH:
Weinheim, Germany, 2011; Vol. 2.
(2) Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart, J. F. Angew. Chem.,
Int. Ed. 2000, 39, 3348−3391.
(3) (a) Kottas, G. S.; Clarke, L. I.; Horinek, D.; Michl, J. Chem. Rev.
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Huang, S. L.; Lin, Y. C.; Sun, W. T.; Yang, J. S. J. Org. Chem. 2011, 76,
1
used for the next step without further purification. H NMR (300
MHz, CDCl3): δ 8.44 (m, 2 H, Har), 8.12 (d, 3JH,H = 9.0 Hz, 2 H, Har),
7.83 (t, 3JH,H = 7.8 Hz, 1 H, Har), 7.66 (m, 2 H, Har), 7.41 (dd, 4JH,H
1.3 Hz, JH,H = 7.3 Hz, 1 H, Har), 7.03 (d, JH,H = 9.0 Hz, 2 H, Har),
3.89 (s, 3 H, CH3), 1.61 (m, 6 H, CH2), 1.36 (m, 6 H, CH2), 1.16 (m,
=
3
3
1894
DOI: 10.1021/acs.joc.5b00026
J. Org. Chem. 2015, 80, 1887−1895

The Journal of Organic Chemistry
Article
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