Control of rotor function in light-driven molecular motors

Article abstract of DOI:10.1021/jo201583z

A study is presented on the control of rotary motion of an appending rotor unit in a light-driven molecular motor. Two new light driven molecular motors were synthesized that contain aryl groups connected to the stereogenic centers. The aryl groups behave

Full text of DOI:10.1021/jo201583z

FEATURED ARTICLE
pubs.acs.org/joc
Control of Rotor Function in Light-Driven Molecular Motors
Anouk S. Lubbe, Nopporn Ruangsupapichat, Giuseppe Caroli, and Ben L. Feringa*
Centre for Systems Chemistry, Stratingh Institute for Chemistry and Zernike Institute for Advanced Materials, University of Groningen,
Nijenborgh 4, Groningen 9747AG, The Netherlands
S Supporting Information
b
ABSTRACT: A study is presented on the control of rotary
motion of an appending rotor unit in a light-driven molecular
motor. Two new light driven molecular motors were synthe-
sized that contain aryl groups connected to the stereogenic
centers. The aryl groups behave as bidirectional free rotors in
three of the four isomers of the 360° rotation cycle, but rotation
of the rotors is hindered in the fourth isomer. Kinetic studies of
both motor and rotor functions of the two new compounds are
given, using 1H NMR, 2D-EXSY NMR, and UVꢀvis spectros-
copy. In addition, we present the development of a new method
for introducing a range of aryl substituents at the α-carbon of
precursors for molecular motors. The present study shows how the molecular system can be photochemically switched between a
state of free rotor rotation and a state of hindered rotation and reveals the dynamics of coupled rotary systems.
’ INTRODUCTION
orientation of the methyl substituents. The four-step cycle provides
full 360° unidirectional rotation of one-half of the molecule with
respect to the other. Since the introduction of motor 1, several
advanced light-driven molecular motors have been designed and
their dynamic properties studied.12 To investigate the unidirectional
rotation of the overcrowded alkene in more detail, the size of the
substituent next to the double bond was varied in “second-genera-
tion” molecular motors.13 Exchanging the methyl group in the
second-generation motor for a more sterically demanding phenyl
group at the stereogenic center in motor 2 (Figure 1) only slightly
Molecular motors are ubiquitous throughout nature and per-
form essential tasks in biological systems.1 Well-known examples
are bacterial flagella,2 kinesine and myosin,3 and ATPase
motors.4 These intricate natural molecular motors have been a
source of inspiration for the development of a variety of artificial
molecular mechanical devices,5 including switches,16,7 shuttles,
muscles, and rotary and translational motors.5 Because potential
applications are highly diverse, artificial molecular motors are
considered extremely useful in powering future nanodevices.8
Dynamic control of a myriad of functions, transmission of
motion in multicomponent systems, and out-of-equilibrium
assembly are important perspectives offered by rotary molecular
motors. Various approaches toward synthetic rotary motors have
been reported, especially systems powered by light9 and chemical
energy.10 A particularly versatile design is based on chiral over-
crowded alkenes. The “first-generation” light-driven molecular
motor 1 (Figure 1) consists of two identical chromophores
linked through a central alkene,11 which serves as the axle of
rotation. This motor contains two stereogenic centers with
methyl substituents in pseudoaxial orientation and the direction-
ality of the rotary motion of 1 is governed by the chirality at these
stereogenic centers in the helical molecule.
increased the barrier for the thermal helix inversion step (t1/2
=
9.8 min at rt) compared to that in the corresponding methyl
substituted analogue (t1/2 = 3.2 min at rt). Light-driven molecular
motor 2 was found particularly suitable to demonstrate transmission
of motion to control the organization of a supramolecular system
and to perform work. Specifically, the photochemical and thermal
isomerizations involved with motor 2, embedded as chiral dopant
in a liquid crystal (LC) film, were used to induce the rotational
reorganization of LC surface textures and rotate a microscale object
on top of the LC film.14 Moreover, it was found that motor 2 with a
phenyl substituent has a higher helical twisting power and enhanced
ability to control the direction of rotational reorganization of the
LC’s surface texture compared to the corresponding motor with a
methyl substituent.14b
With this system, the unidirectional 360° rotation of the upper
half relative to the lower half in the molecular motor is performed
through a four-step switching cycle. There are two irradiation
steps (energetically uphill), during which photochemical cisꢀtrans
isomerization occurs, forcing the methyl substituents in an un-
favorable pseudoequatorial position. Each photoisomerization
step is followed by an irreversible thermal isomerization step
(energetically downhill) that re-establishes the favorable pseudoaxial
Another notable example of a functional molecular motor
is the so-called “molecular gearbox” motor 3 (Figure 1).15 In this
system, two rotary units are present, representing two coupled
dynamic functions. Molecule 3 contains a freely rotating
Received: August 9, 2011
Published: September 19, 2011
r
2011 American Chemical Society
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Figure 1. Design features of first- and second-generation rotary motors and coupled rotary systems: first-generation molecular motor 1, second-
generation motor 2 with phenyl substituent at the stereogenic center, “molecular gearbox” 3, and molecular motors 4 and 5 with phenyl and m-
methoxyphenyl groups at the stereogenic centers, respectively.
Scheme 1. New Synthetic Pathway for the α-Aryl Ketone Upper-Half
1,5-dimethylphenyl group attached to the stator unit, which
behaves as a bidirectional rotor unit.5 It was found that the rate
of rotation of the rotor moiety (1,5-dimethylphenyl) in this
molecular system was different for each of the four isomers
formed during a full 360° rotary cycle of the motor. This rotor
control is considered an important step in the development of
future coupled rotary systems.6 In these two examples, the
aromatic group in the motor structure has played an important
role to perform distinct functions. A major question arises
regarding the first-generation motors: if the methyl groups in
1 are replaced by aromatic groups (as in 4 and 5) at the stereo-
genic centers of a first-generation molecular motor (Figure 1),
will it still be possible to control coupled dynamic functions as
described above?
We present here new molecular motors 4 and 5 to address this
pertinent question and to further study the dynamic properties of
coupled rotary systems. Both of these molecules were designed
based on the structures 1ꢀ3, but for motor 4 the methyl groups
are exchanged for phenyl groups, and for 5 m-methoxyphenyl
groups are present at the stereogenic centers (structures 4 and 5
illustrate the modifications introduced to first-generation motor
1, Figure 1). These aryl substituents are expected to behave as
bidirectional rotors, as observed for motor 3. Using UVꢀvis and
temperature-dependent NMR spectroscopy, we are able to show
that 4 and 5 function as first-generation motors and that in these
molecules the rotation of the rotor part is coupled to the
unidirectional rotation of the motor part. The design of motors
4 and 5 is anticipated to provide a convenient handle for
analyzing the rotation of the rotor moiety (at the stereogenic
center) using dynamic (EXSY) NMR experiments. In this paper,
we focus on studies toward the rate of rotation (k) of the rotor
moiety including the behavior of light-driven rotary molecular
motors. Likewise, we present a study toward the development of
a new method for introducing a range of new substituents at the
α-carbon of ketones (precursors for molecular motors). This
new design is the key to achieving conclusive evidence of the
coupled rotation while still preserving the proper light-driven
motor function.
’ RESULTS AND DISCUSSION
In our synthetic approach toward target molecules 4 and 5, we
anticipated developing a short procedure to prepare a number of
different α-aryl substituted ketones 6 as precursors being part of a
more general route to “first-generation” aryl-substituted molec-
ular motors. As we reported previously, the upper-half α-phenyl
ketone 6.3 (Scheme 1) can be synthesized in six steps (in an
overall yield of 30%) from methyl 2-bromo-2-phenylacetate.13
This procedure does not allow for facile synthesis of motors with
different aryl substituents introduced at the α-position. Here, we
present a new synthetic route toward various α-aryl substituted
ketones 6. This new route consists of two steps and therefore
allows us to easily vary the aryl substituents at the α-position.
Consequently, several α-aryl-substituted ketones 6 have been
synthesized and the reaction conditions have been optimized.
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Table 1. α-Arylation Reaction Using Pd(OAc)2 and XPhos with Different Aryl Halides
a Smaller amounts of Pd(OAc)2/XPhos (1/2 mol %, 5/10 mol % and 20/40 mol %) did not result in product formation or produced poor yields. b The
aryl halide was prepared in one step from iodobenzyl alcohol with tert-butyldiphenylsilyl chloride (t-BDPSCl).
Although the development of an efficient method for the
formation of a bond between an aryl moiety and the α-carbon
of a carbonyl compound has long been a challenging problem in
organic synthesis, Buchwald16 and co-workers have reported the
α-arylation of ketones via palladium catalyzed reaction. This
methodology forms the basis for the shorter synthetic route
toward α-aryl substituted ketones 6 described here.
The two-step synthetic approach toward the desired α-aryl-
substituted ketones is shown in Scheme 1. The first step involves
a FriedelꢀCrafts acylation of the naphthalene with β-chloropro-
pionyl chloride, leading to ketone 7. The results of the subse-
quent Pd-catalyzed α-arylation reaction using XPhos17 as ligand
for a variety of conditions and aryl compounds are shown in
Table 1.
1-iodo-2,6-dimethylbenzene, and iodobenzene to provide α-aryl
ketones 6.1ꢀ6.3 in yields up to 70% (entries 1ꢀ3). We have also
observed the arylation reaction with an electron donating group
(EDG) present at the phenyl moiety, as shown for m- and p-
iodoanisole (entries 4 and 5). It is evident that the arylation
reaction is dependent on the position of the methoxy group on
the aryl halide reagent. The use of p-iodobenzyl bromide, which
has acidic benzylic protons, resulted in side products (possibly
from the SN2 reaction) rather than the desired product (entry 6).
In order to further functionalize the aryl moiety, we have also
performed the arylation reaction with tert-butyl(3-iodobenzyloxy)
diphenylsilane, providing aryl ketone 6.7 in 64% (entry 7).
These results illustrate that it is possible to synthesize the
α-arylated ketone upper-half in two steps from naphthalene.
Future optimization of this new procedure, especially for large-
scale synthesis, is required in view of the rather large amount
of palladium catalyst and ligand that is used in the α-arylation
reaction. Although these arylation reactions so far need a higher
In order to establish the optimal arylation conditions
(Table 1), the amount of Pd/XPhos was varied (Table S1,
Supporting Information). The use of 50/100 mol % of Pd/
XPhos resulted in arylation of 1-iodo-3,5-dimethylbenzene,
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Scheme 2. Synthesis of “First-Generation” Light-Driven Molecular Motors 4 and 5
and 1H NMR spectroscopy is first described. This is followed by a
study of the rotation of the aryl moieties (the rotor function) of
these compounds by 2D-EXSY NMR spectroscopy.
Photochemical and Thermal Behavior of Molecular Motor
4. The overcrowded alkene 4 can undergo a full 360° unidirec-
tional rotation of one-half of the molecule relative to another half
upon irradiation followed by a thermal helix inversion process
(Scheme 3).
Scheme 3. Rotary Cycle of “First-Generation” Molecular
Motor 4
The thermal and photochemical steps in the rotation process
1
of 4 were studied by H NMR spectroscopy. Figure 2a shows
the spectrum of a solution of stable cis-4 in dichloromethane-d2
at ꢀ50 °C. Distinctive features are absorptions of the aliphatic
protons Ha, Hb, and Hc. Only negligible coupling is expected
between Ha and Hb. Therefore, the absorption at 3.9 ppm is
assigned to Hc. As the coupling constant is expected to be larger
for geminal protons than for vicinal protons, the absorption at
2.9 ppm (J = 15.4 Hz) is assigned to Hb, and the absorption at
4.5 ppm (J = 6.9 Hz) is assigned to Ha.
Irradiation at λ g 365 nm of the solution of stable cis-4
(at ꢀ75 °C) resulted in the formation of a new isomer, assigned
unstable trans. All absorptions shifted, most notably the doublet
absorptions at 2.9 ppm (Hb) and 3.9 ppm (Hc). These absorp-
tions are shifted downfield and upfield, respectively, and appear
together as two multiplets at 3.3 and 3.5 ppm. Extended
irradiation results in a photoequilibrium which strongly favors
the formation of unstable trans-4 (92:8, unstable trans/stable cis)
as is evident from the 1H NMR spectra shown in Figure 2a,b. An
interesting observation is that in Figure 2b all five protons of the
phenyl moiety absorb at a different chemical shift (four in the
region 6.4ꢀ6.7, one at 7.25 ppm). This indicates that the phenyl
group is not rotating freely.
Subsequently, the sample was heated to 0 °C for 15 min to
induce thermal helix inversion, whereby the conformational
strain due to the pseudoequatorial orientation of the phenyl
moiety in unstable trans-4 is released. A 1H NMR spectrum was
recorded at ꢀ50 °C (Figure 2c). Again, all absorptions shifted
and the absorptions of Hb and Hc can be found at 2.7 ppm
(d, Hb) and 3.5 ppm (m, Hc), and the new isomer is assigned
stable trans-4. In this isomer, the phenyl groups at the stereogenic
center adopt a favored pseudoaxial orientation.
loading of palladium catalyst and ligand than anticipated,16 it is a
significally more efficient route than the original six-step proce-
dure in terms of yield and time.13 Moreover, we found it to be a
valuable alternative for small scale synthesis to access a range of
different α-aryl substituted ketones suitable as molecular motor
precursors to be tested in several applications.
Synthesis of the Molecular Motors. Because of severe steric
hindrance in the structures of 4 and 5, most olefination reactions
are not suitable for the formation of the central olefinic bond in
these molecules. We were pleased to find that sterically over-
crowded alkenes 4 and 5 were prepared in one step by a
McMurry coupling reaction of the corresponding ketone as
shown in Scheme 2. Ketones 6.3 and 6.4 were coupled in the
presence of TiCl4 and zinc powder by refluxing in THF over-
night, providing alkene 4 in 16% yield and alkene 5 in 35% yield,
both as a mixture of cis and trans isomers.
The sample was irradiated for a second time (λ g 365 nm,
4 h, ꢀ75 °C), and a 1H NMR spectrum was recorded at ꢀ50 °C
(Figure 2d). All absorptions shifted again, and no residual stable
trans-4 was visible, implying full conversion. The absorptions of
Hb and Hc can be found as two multiplets at 3.3 and 3.5 ppm, and
the new isomer is assigned unstable cis-4 (unstable cis > 95/stable
trans < 5). It is noted that for this isomer, as well as in stable cis-4
and stable trans-4, the absorptions of the phenyl moiety appear as
a single peak at ∼7.2 ppm, implying free rotation around the
Separation of the isomers of motors 4 and 5 was achieved with
flash column chromatography and provided pure stable cis-4
(5%) and stable trans-4 (11%) and pure stable cis-5 (14%) and
stable trans-5 (21%), respectively. The assignment of the struc-
tures of cis and trans 4 and 5 is based on related "first-generation"
motors and is supported by calculations (Figures S1 and S2,
Supporting Information). To analyze the light-driven motor
function, the photochemical and thermal behavior of compounds
4 and 5 as determined by UVꢀvis spectroscopy, kinetic analysis
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Figure 2. 1H NMR spectra (500 MHz) of 4 in CD2Cl2: (a) stable cis-4; (b) unstable trans-4 formed upon photochemical isomerization (λ g 365 nm);
(c) stable trans-4 obtained after thermal helix inversion of unstable trans-4 at rt; (d) unstable cis-4 formed upon irradiation (λ g 365 nm) (all spectra
were recorded at ꢀ50 °C).
single bond connecting the phenyl group to the stereogenic
center of 4. A second thermal helix inversion (30 °C, 30 min)
ultimately regenerated stable cis-4 (spectrum Figure 2a), thereby
completing the 360° rotation around the central double bond.
Kinetic analysis was performed on both thermal helix inver-
sions. For unstable trans-4 f stable trans-4, ΔqG° was calculated
absorption (Figure 2a,c,d). Consequently, the phenyl substituent
of motor 4 might be used as a switching system (between free and
slow rotation) accompanying the motor switching between the
stable cis and unstable trans isomers.
Unfortunately, because of overlap in the aromatic region of the
1H NMR spectrum between the absorptions of the rotor
(phenyl) and the absorptions of the naphthalene moieties, the
rotor properties could not be studied in more detail. Further
research into the rotation of the bidirectional rotor was therefore
conducted on molecular motor 5, which has a methoxy-sub-
stituted rotor unit.
to be 78 kJ molꢀ1 (t1/2 = 9.4 s at rt), and for unstable cis-4 f
3
stable cis-4, ΔqG° = 98 kJ molꢀ1 (t1/2 = 8.2 h at rt) was obtained.
3
These data reveal that the half-life (t1/2 = 9.4 s) of unstable to
stable trans-4 is not very different compared to the analogue with
the methyl substituent (unstable trans-1 f stable trans-1) at the
stereogenic center (t1/2 = 18 s at rt).11 In contrast, the thermal
isomerization step of unstable cis-4 to stable cis-4 (t1/2 = 8.2 h at
rt) is much slower than the corresponding isomerization of the
analogous unstable cis-1 f stable cis-1 (t1/2 = 74 min at rt).
An interesting feature of this motor 4 is that free rotation of the
phenyl “rotor” moiety (at the stereogenic center) is observed in
three of the four isomers (stable cis-, stable trans-, and unstable
cis-) during a 360° cycle, but the rotation is hindered in the fourth
isomer (unstable trans-4). 1H NMR data of motor 4 show that
the free rotation of the phenyl group is hindered in the unstable
trans isomer because of the significant steric hindrance of the
naphthalene moiety in the opposite half of the motor. This is
the reason why five protons of the phenyl rotor moiety in unstable
trans-4 show five distinct absorptions as shown in Figure 2b;
the rotation is slow at the NMR time scale as compared with the
other isomers. In stable cis-, stable trans- and unstable cis-4 all the
five protons of the phenyl “rotor” moiety are observed as a single
Photochemical and Thermal Behavior of Molecular Motor
5. Before studying the dynamic properties of the rotor part (m-
methoxyphenyl) of motor 5, the motor function itself was
examined. Initial studies on the behavior of the motor unit were
performed with the stable isomers18 of cis-5 and trans-5 and the
photochemical isomerization and thermal helix inversion pro-
1
cesses were analyzed by UVꢀvis and H NMR spectroscopy.
Likewise, it was anticipated that motor 5 should function as a
light-driven molecular rotary motor which proceeds through a
four-step switching cycle, similar to the cycle of motor 4
(Scheme 3).
A solution of stable cis-5 (3.7 ꢁ 10ꢀ5 M) in dichloromethane
and a solution of stable trans-5 (3.0 ꢁ 10ꢀ5 M) in 1,2-dichlo-
roethane19 were used for the UVꢀvis spectroscopic studies.
Starting with stable cis-5 at ꢀ20 °C, a photochemical isomeriza-
tion (with UV light g 365 nm) generates unstable trans-5
and the UVꢀvis absorption spectrum was measured at regular
intervals until the photostationary state (PSS) was reached. An
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Figure 3. UVꢀvis spectra of molecular motor 5: (a) photoisomerization and thermal helix inversion steps from stable cis- to stable trans-5; (b)
photoisomerization and thermal helix inversion steps from stable trans- to stable cis-5.
isosbestic point was formed at 380 nm and a red-shift of the
In addition, UVꢀvis spectroscopy was used to study the
kinetics of the two thermal isomerization steps. The changes in
UVꢀvis absorption at 410 nm were monitored as a function of
time at different temperatures (ꢀ5, ꢀ10, ꢀ12, ꢀ15, and ꢀ20 °C
for unstable trans-5 f stable trans-5; 30, 40, 50, and 60 °C for
unstable cis-5 f stable cis-5). Using these data, an Eyring plot
was made for both thermal steps, from which the half-life and
Gibbs free energy of activation were calculated. It was found that
maximum at 375 nm (ε = 15.8 ꢁ 103 dm3 molꢀ1 cmꢀ1) (to
3
3
387 nm (ε = 15.8 ꢁ 103 dm3 molꢀ1 cmꢀ1)) was observed. The
3
3
bathochromic shift can be attributed to the generation of an
unstable trans isomer, where the ground state is destabilized
compared to the stable trans isomer due to increased strain.11
This decreases the energy gap, as seen with other first-generation
molecular motors (dotted line, Figure 3a). The sample was then
left for 100 min at ꢀ20 °C to allow the thermal helix inversion
process to occur. The UVꢀvis spectrum indicates that the
unstable trans-5 has converted to stable trans-5 (λmax = 375 nm,
ε = 16.8 ꢁ 103 dm3 molꢀ1 cmꢀ1, dashed line, Figure 3a). On the
t1/2 = 9.45 s at rt (ΔqG° = 78.14 kJ molꢀ1; see Figure S3a,
3
Supporting Information) for the isomerization of unstable trans-
5 to stable trans-5, a value similar to that of the analogous helix
inversion of the related motor 4 which was determined to be 9.4 s
at rt. The t1/2 of unstable cis-5 to stable cis-5 is 6.2 h (ΔqG° =
3
3
basis of these data it can be concluded that one-half of the rotary
cycle (180°) has been completed (stable cis f stable trans).
Figure 3b shows the UVꢀvis spectra of the isomers observed
duringthe otherhalf of the 360° rotary cycle from stable trans-5 via
unstable cis-5 to stable cis-5. A UVꢀvis spectrum of stable trans-5
was acquired at rt. As expected, this spectrum (Figure 3b, solid
line) is similar to the spectrum obtained after the thermal
isomerization step as shown in Figure 3a (dashed line).
97 kJ molꢀ1, at rt) (see Figure S3b, Supporting Information).
3
This thermal isomerization step is slightly faster than the isom-
erization of the analogous unstable cis-4 to stable trans-4 (t1/2
=
8.2 h, at rt).
1H NMR Measurements of Molecular Motor 5. The iso-
merization steps during the rotation process of motor 5 were
studied in more detail by 1H NMR spectroscopy. Solutions18 of
pure stable trans-5 and stable cis-5 isomers in dichloromethane-
d2 were both irradiated with UV light (λ g 365 nm) at ꢀ40 °C.
Distinctive features in the 1H NMR spectrum of stable trans-5
(Figure 4a) are absorptions of the aliphatic protons at
2.75 ppm (d, Hb), 3.48 ppm (dd, Hc), and 4.21 ppm (d, Ha).
Upon irradiation of the solution of stable trans-5, the doublet
absorption at 2.75 ppm is shifted downfield and the double
doublet at 3.50 is shifted upfield so these absorptions appear
together at 3.23ꢀ3.45 ppm (m, Hb + Hc) (Figure 4b). Compar-
ison with data obtained for motor 4 confirms that the unstable cis
isomer is formed. In addition, no residual trans isomer is left in
the solution, so the photochemical isomerization step gives a
conversion >95% toward unstable cis-5. A subsequent thermal
helix inversion (at rt, overnight) produced stable cis-5, but also a
considerable amount of stable trans-5 (cis/trans ratio 43:57) was
observed (Figure 4c). In contrast, performing the thermal step at
40 °C for 2 h gave a different ratio of stable cis and stable trans
isomers (cis/trans ratio 77:23) (Figure 4d). To confirm these
results, the stable trans to stable cis isomerization was examined
The solution of stable trans-5 (λmax = 360 nm, ε = 17.6 ꢁ 103
dm3 molꢀ1 cmꢀ1) was then irradiated with UV light
3
3
(g365 nm) at 40 °C until the PSS was reached. In the UVꢀvis
spectrum of unstable cis-5 (λmax = 401 nm, ε = 8.3 ꢁ 103
dm3 molꢀ1 cmꢀ1, dotted line, Figure 3b), the expected red-
shift was observed once again and a clear isosbestic point was
displayed at 385 nm. Subsequently, the sample was left at 40 °C
for 5 h. The final spectrum (λmax = 377 nm, ε = 12.8 ꢁ 103
dm3 molꢀ1 cmꢀ1, dashed line, Figure 3b) is similar to the
3
3
3
3
spectrum of stable cis-5 in Figure 3a (solid line) and it can be
concluded that the other half of the 180° rotary cycle has been
completed. However, the spectra of stable cis shown in Figure 3b
(dashed line) and Figure 3a (solid line) are not completely
identical, as was also observed for stable trans (Figure 3a, dashed
line and Figure 3b, solid line). This indicates that, although the
isomerization step proceeds as expected, the conversion in both
halves of the cycle is less than 100%. Further 1H NMR studies will
provide more information about the actual conversion during the
photochemical and thermal isomerization processes (vide infra).
1
in a different solvent by H NMR measurements. After the
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Figure 4. 1H NMR spectra (500 MHz) of 5 in CD2Cl2: (a) stable trans-5; (b) unstable cis-5 obtained by photochemical isomerization (λ g 365 nm)
from stable trans-5; (c) stable cis-5 obtained by thermal helix inversion from unstable cis-5 at rt; (d) stable cis-5 obtained by thermal helix inversion from
unstable cis-5 at 40 °C (all spectra were recorded at ꢀ40 °C).
photochemical isomerization step of stable trans-5 in toluene-d8
(unstable cis > 95%), 1H NMR spectra were recorded first at rt,
and it was found that under these conditions the unstable cis-5
undergoes a forward isomerization to stable cis-5 as well as a
competing backward isomerization to the stable trans isomer
(stable cis/stable trans ratio, 63:37). When unstable cis-5 (>95%)
in toluene-d8 was used at higher temperatures, it was observed
that the thermal isomerization process of unstable cis-5 at 70 °C
gave a considerable amount of stable cis-5 (cis/trans ratio, 76:24)
(see Figure S2, Supporting Information). Formation of the stable
trans isomer means that isomerization from unstable cis-5 to
stable cis-5 is not a completely unidirectional rotation process
(reversible). Even in a different solvent and at different tempera-
tures, the unstable cis isomer still shows competition between
forward rotation to stable cis-5 and backward rotation to stable
trans-5. This behavior of molecular motors showing a compe-
ting backward thermal helix inversion was also observed for
some other systems,20 and the consequences for the unidirec-
tional nature of the overall motor function were expressed in a
mathematical model.21 The present system shows similar beha-
vior and the competing backward thermal helix inversion is the
consequence of the replacement of the substituent at the
stereogenic center and the relatively high barrier for thermal
isomerization. From these results, it is evident that the ratio of
stable cis and trans isomers depends on the temperature at which
the thermal helix inversion process takes place.21 Nevertheless,
there is a large preference for the forward direction, which allows
a major unidirectional rotary motion.
The next step in the rotary cycle was performed with stable cis-
5; two of the three aliphatic protons of stable cis-5 (CD2Cl2,
ꢀ40 °C) are found at 2.95 ppm (d, Hb) and at 3.85 ppm (dd, Hc)
as shown in Figure 5a. Irradiation of stable cis-5 resulted in a
downfield shift of the absorption of Hb from 2.95 to 3.25 ppm
and upfield shift of the absorption of Hc from 3.85 to 3.50 ppm
(Figure 5b). Formation of the unstable trans isomer was also
confirmed by comparison with data obtained for motor 4. More-
over, in this spectrum of unstable trans-5, the decrease in the rate
of rotation of the rotor part (m-methoxyphenyl) is clearly visible.
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Figure 5. 1H NMR spectra (500 MHz) in CD2Cl2 at ꢀ40 °C of (a) stable cis-5 and (b) unstable trans-5 after irradiation (λ g 365 nm) showing the
distinct absorption for the methoxy group (A and B).
Scheme 4. Rotamers A and B of Unstable trans-5
For all three other isomers (stable trans, stable cis, and unstable
cis), the singlet of the methoxy group appears at 3.6 ppm (s, 3H).
However, in the spectrum of unstable trans-5, this absorption
appears as two singlets at around 3.40ꢀ3.45 ppm. This implies
that the rotation of the rotor moiety is slow on the NMR time
and thermal isomerization steps (from stable cis to stable trans
isomers) result in a 180° rotation of the upper half of the molecule
with respect to the other half (as for 4 in Scheme 3).
2D-EXSY Measurements for the Rotor Functions of the
Molecular Motor. Initial studies of the rate of rotation of the
rotor moiety were carried out with the unstable trans isomer,
generated by photoisomerization of stable cis-5. However, be-
cause of the high activation barrier of the rotor, coalescence
studies using 1H NMR are not suitable to determine the rate of
exchange (rate of rotation, k) of the anisole group.23 Because the
half-life of unstable trans-5 to stable trans-5 is very short at rt,
thermal isomerization occurs before the rotation of the rotor unit
can be examined. Therefore, the exchange of the methoxy group
of the m-methoxyphenyl substituent is only visible on the NMR
time scale at low temperature. 2D-EXSY spectra of unstable trans-
5 were obtained at different temperatures of ꢀ50, ꢀ45, ꢀ40, and
ꢀ35 °C, with different mixing times of 0.1, 0.2, 0.3, 0.5, 0.7, 0.9,
and 1.1 s in dichloromethane-d2. Figure 6a shows a 2D-EXSY
spectrum (see general remarks). The presence of exchange cross
peaks immediately showed that, as expected, the rotation of the
rotor around the biaryl bond connecting the rotor moiety to the
motor in the unstable trans isomer is hindered.24,25
1
scale, which in turn implies that H NMR spectroscopy can be
used to distinguish between two different relative positions
(A and B) of the methoxy substituent in this isomer and to
1
establish the barrier of rotation by temperature dependent H
NMR measurements (Scheme 4).
1
In the H NMR spectrum of unstable trans-5 at ꢀ40 °C,22
some residual stable cis-5 is still visible after irradiation, and the
PSS was calculated to consist of 75% of unstable trans-5 and 25%
of stable cis-5 (see Figure S5b, Supporting Information). The 1H
NMR spectrum of the sample after heating (20 °C for 20 min)
revealed that all of the absorptions of unstable trans-5 were
replaced by the absorptions expected from stable trans-5, ex-
emplified by the shift of one of the protons in the aliphatic region
from 3.25 to 2.75 ppm (see Figure S5c, Supporting Information).
These 1H NMR data indicated that the thermal isomerization of
unstable trans-5 quantitatively gave stable cis-5, and as a con-
sequence, a ratio of stable trans-5 to stable cis-5 of 75:25 was
found. This means that this thermal isomerization from stable cis-5
to stable trans-5 is a unidirectional process. These photochemical
Unstable trans-5 can be approached as an asymmetrical two-site
exchange system between a proton and a methoxy at the m-anisole
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FEATURED ARTICLE
Figure 6. (a) 2D-EXSY spectrum of unstable trans-5 (500 MHz, CD2Cl2) at ꢀ40 °C (mixing time 0.2 s). (b) Graph showing the relation between
mixing time and the ratio between cross (proton 1A) and diagonal peaks (proton 1B) for unstable trans-5 at ꢀ35 °C (top line, empty squares), ꢀ40 °C
(second line, filled squares), ꢀ45 °C (third line, empty circles), and ꢀ50 °C (bottom line, filled circles).
moiety (Scheme 4). By rotating around a single bond that
connects the rotor (m-anisole) to the motor, the methoxy group
exchanges its position with that of the proton on the other side of
the phenyl moiety. One of these conformations is higher in energy
than the other because of steric interaction between the methoxy
group and the naphthalene moiety. This means the conformations
will not be equally populated and, therefore, the ratio of cross
peaks and diagonal peaks will not converge to 1.
First-generation molecular motors with phenyl and m-anisole
groups at the stereogenic centers have been synthesized, and the
dynamic behavior of these new first-generation molecular motors
has been studied in detail. Even though the UVꢀvis studies
confirm the four-step rotary cycle and 1H NMR studies show that
conversion for both photochemical steps is near 100%, the
thermal step from unstable cis to stable cis in the rotary cycle is
not completely unidirectional for motor 5. A major goal of this
study was to examine how the rotary motion of an appending
rotor unit can be controlled by the light-driven motor function. It
has been demonstrated that the rate of rotation of the m-anisole
rotor embedded in these molecular motors can be controlled
using light and heat as external triggers. The rotation properties
This can be resolved by adding an extra parameter p to the
equation (eq 1; see the Experimental Section, general remarks)
when fitting a line to the data points in Figure 6b. Parameter p
represents the population of one of the exchange sites, the
population of the other site being 1 ꢀ p. In case of symmetrical
exchange, p is 0.5. Because the ratio of cross peaks and diagonal
peaks is directly proportional to the population of the exchange
sites, the peak ratio will approach to p/(1 ꢀ p). In this case this is
0.23, as can be observed in Figure 6b, where peak ratios are plotted
versus mixingtimes. From the peak ratio, the extra parameter p can
be calculated for the rotor part of molecular motor 5 to be 0.19.26
From this graph, the Gibbs free energy of activation (ΔqG°)
1
of the m-anisole moiety have been studied in detail using H
NMR and 2D-EXSY spectroscopy. The results show that the
rotation of the m-anisole moiety in 5 is unhindered in the stable
trans, unstable cis, and stable cis isomers but hindered in the
unstable trans isomer. Therefore, the system can be used as a
light-switch between a state of free rotor rotation and a state of
hindered (slow) rotor rotation. Our findings on the control of the
speed of rotation of the rotors will be useful in the design of more
advanced molecular motors, in particular to control coupled
motion.
for the rotation of the rotor was calculated to be 11.6 kJ molꢀ1
.
3
Using the Eyring equation, the rate of exchange (rate of rotation; k)
has been calculated to be 8.1 ꢁ 109 sꢀ1 at 20 °C. The 1H NMR
spectra of the other three isomers (stable trans, unstable cis ,and
stable cis) show that the rotation of the rotor part is unhindered (free
rotation around the single bond). This means that motor 5 behaves
as a coupled rotary system. By simple isomerization from stable cis-5
to unstable trans-5, the rotation rate of the bidirectional rotor can be
altered significantly. Thermal helix inversion to stable trans-5 or
photoisomerization to stable cis-5 returns the rotor to its original,
unhindered state. Although this molecular motor 5 is not as
sophisticated as the “second-generation” molecular gearbox 3, this
motor can be used as a rotation-on-rotationꢀoff switching system
by photoisomerization from stable cis-5 to unstable trans-5 and back
again (Scheme 4). Due to its simple design, this will be a very useful
function in more advanced coupled rotary systems.
’ EXPERIMENTAL SECTION
General Remarks. All reactions were carried out in oven-dried
glassware under a nitrogen atmosphere. Solvents were reagent grade,
distilled and dried before use according to standard procedures. Other
commercially available reagents were used without purification. Irradia-
tion experiments were performed using an ENB-280C/FE lamp (λ g
365 nm). Samples irradiated for 1H NMR spectroscopic analysis were
placed 2ꢀ3 cm from the lamp. Photostationary states were determined
by monitoring composition changes into time by taking UVꢀvis spectra
or 1H NMR spectra at distinct intervals until no additional changes were
observed. Kinetic analysis of the thermal isomerization steps was
performed by UVꢀvis spectroscopy. A high-pass filter was mounted
in front of the UV light source to cut off all light with a wavelength below
380 nm to minimize photochemical isomerization occurring upon data
recording. Changes in UVꢀvis absorptions were measured at different
temperatures: for unstable trans- to stable trans-isomers in DCM at ꢀ20,
ꢀ15, ꢀ12, ꢀ10, and ꢀ5 °C and for unstable cis- to stable cis-isomers in
DCE at 30, 40, 50, and 60 °C. From the obtained data the rate constants
(k) were obtained and an Eyring plot was made for both thermal steps
’ CONCLUSIONS
In summary, a new synthetic route toward functionalized first-
generation molecular motors has been developed, reducing the
number of synthetic steps from seven to three. A number of
different aryl-substituted ketone precursors for first-generation
motors are readily accessible.
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FEATURED ARTICLE
and ΔqH°, ΔqS°, ΔqG, and t1/2 (at 20 °C) of both cis- and trans-
isomerizations were calculated from these data.
and the mixture was extracted with diethyl ether (3 ꢁ 25 mL), washed
with water (25 mL), dried (Na2SO4), filtered, and concentrated in vacuo.
The crude product was purified by flash column chromatography (SiO2,
pentane: EtOAc; 9: 1, Rf = 0.58). Ketone 6.1 was obtained as a brown
powder (0.32 g, 1.18 mmol, 62%): 1H NMR (400 MHz, CDCl3) δ 2.28
(s, 6H), 3.34 (dd, J = 15.4, 5.4 Hz, 1H), 3.70ꢀ3.80 (m, 1H), 3.91 (dd, J =
9.7, 4.8 Hz, 1H), 6.83 (s, 2H), 6.90 (s, 1H), 7.54ꢀ7.61 (m, 2H),
7.64ꢀ7.72 (m, 1H), 7.92 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.5 Hz, 1H),
9.16 (d, J = 8.7 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 21.3 (CH), 36.3
(CH2), 53.8 (CH3), 123.8 (CH), 124.2 (CH), 125.6 (CH), 126.7 (CH),
128.1 (CH), 128.7 (CH), 129.0 (CH), 129.7 (C), 130.2 (C), 132.9 (C),
136.1 (CH), 138.4 (C), 139.9 (C), 157.2 (C), 206.7 (C); HRMS (ESI)
m/z calcd for C21H18O 286.3670, found 286.3633.
2-(2,6-Dimethylphenyl)-2,3-dihydro-1H-cyclopenta[a]naphthalen-
1-one (6.2). Ketone 6.2 was prepared via general procedure A from
ketone 7 (117 mg, 0.65 mmol) and 1-iodo-2,6-dimethylbenzene (100
mg, 0.43 mmol) using Pd(OAc)2 (48 mg, 0.22 mmol), t-BuONa (120
mg, 1.29 mmol), and 2-dicyclohexylphosphino-20,40,60-triisopropylbi-
phenyl (210 mg, 0.43 mmol). The crude product was purified using flash
column chromatography (SiO2, pentane/EtOAc 9:1, Rf = 0.55). Ketone
6.2 was obtained as a pale yellow powder (82 mg, 0.29 mmol, 67%): 1H
NMR (400 MHz, CDCl3) δ 1.91 (s, 3H), 2.48 (s, 3H), 3.25 (dd, J = 17.5,
4.5 Hz, 1H), 3.74 (dd, J = 17.9, 8.1 Hz, 1H), 4.38 (dd, J = 8.0, 4.8 Hz,
1H), 7.00 (t, J = 4.5 Hz, 1H), 7.10 (d, J = 4.7 Hz, 2H), 7.54ꢀ7.63 (m,
2H), 7.70 (t, J = 7.6 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 8.11 (d, J = 8.4 Hz,
1H), 9.24 (d, J = 8.4 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 21.3
(CH), 34.2 (CH2), 50.4 (CH3), 123.8 (CH), 124.1 (CH), 126.7 (CH),
126.9 (CH), 128.12 (CH), 128.14 (CH), 128.9 (CH), 129.4 (CH),
130.8 (C), 132.9 (C), 135.8 (CH), 136.4 (C), 137.8 (C), 155.5 (C),
207.0 (C); HRMS (ESI) m/z calcd for C21H19O 287.1430, found
287.1439.
2-Phenyl-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-one (6.3).
Ketone 6.3 was prepared via general procedure A from ketone 7 (0.13
g, 0.74 mmol) and iodobenzene (0.1 g, 0.49 mmol) using Pd(OAc)2
(55 mg, 0.25 mmol), t-BuONa (0.14 g, 1.47 mmol), and 2-dicyclohex-
ylphosphino-20,40,60-triisopropylbiphenyl (0.23 g, 0.49 mmol). The crude
product was purified using flash column chromatography (SiO2, pentane/
EtOAc; 85:15, Rf = 0.54). Ketone 6.3 was obtained as a brown powder
(88.5 mg, 0.34 mmol, 70%): 1H NMR (400 MHz, CDCl3) δ 3.36 (dd,
J = 17.9, 3.4 Hz, 1H), 3.75 (dd, J = 17.9, 7.9 Hz, 1H), 3.99 (dd, J = 7.9,
3.4 Hz, 1H), 7.24ꢀ7.30 (m, 3H), 7.33ꢀ7.38 (m, 2H), 7.55ꢀ7.61
(m, 2H), 7.69 (t, J = 7.6 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 8.10 (d, J =
8.4 Hz, 1H), 9.19 (d, J = 8.3 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ
36.2 (CH2), 53.9 (CH), 123.8 (CH), 124.1 (CH), 126.8 (CH), 127.0
(CH), 127.9 (CH), 128.2 (CH), 128.9 (CH), 129.1 (CH), 129.7 (C),
130.2 (C), 132.9 (C), 136.2 (CH), 140.0 (C), 157.1 (C), 206.4 (C);
HRMS (ESI) m/z calcd for C19H14O 258.1045, found 258.1041.
2-(3-Methoxyphenyl)-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-
one (6.4). Ketone 6.4 was prepared via general procedure A from ketone
7 (0.57 g, 3.1 mmol) and 1-iodo-3-methoxybenzene (0.61 g, 2.6 mmol)
using Pd(OAc)2 (0.29 g, 1.3 mmol), t-BuONa (0.62 g, 6.4 mmol), and
2-dicyclohexylphosphino-20,40,60-triisopropylbiphenyl (1.2 g, 2.6 mmol).
The crude product was purified using flash column chromatography
(SiO2, pentane/EtOAc; 4:1, Rf = 0.45). Ketone 6.4 was obtained as a
yellow oil (0.31 g, 1.09 mmol, 35%): 1H NMR (400 MHz, CDCl3) δ 3.36
(dd, J = 17.8, 3.4 Hz, 1H), 3.72ꢀ3.81 (m, 4H), 3.97 (dd, J = 7.9, 3.4 Hz,
1H), 6.77ꢀ6.85 (m, 3H), 7.21ꢀ7.29 (m, 1H), 7.55ꢀ7.60 (m, 2H), 7.68
(ddd, J = 8.3, 7.0, 1.3 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 8.11 (d, J = 8.4 Hz,
1H), 9.15 (d, J = 8.4 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 36.1
(CH2), 53.8 (CH), 55.2 (CH3), 112.3 (CH), 113.8 (CH), 120.1 (CH),
123.7 (CH), 124.1 (CH), 126.8 (CH), 128.1 (CH), 129.1 (CH), 129.7
(C), 129.8 (CH), 130.2 (C), 132.9 (C), 136.2 (CH), 141.5 (C), 157.1
(C), 159.9 (C), 206.2 (C); HRMS (ESI) m/z calcd for C20H16O2
289.1223, found 289.1208 (M + H+).
For the 2D-EXSY measurements, signals on the diagonal line are
referred to as “diagonal peaks”; these are the two-dimensional depiction
of the 1H NMR spectrum of the compound. Signals deviating from this
line are called “cross peaks”. Every cross peak can be connected to two
corresponding diagonal peaks and one other cross peak, and this set of
absorptions is indicative of an exchange process. By assigning and
integrating the cross peaks and corresponding diagonal peaks, informa-
tion about exchange processes in the compound 5 can be obtained
(for details, see ref 25).
A cross peak and one of its corresponding diagonal peaks were then
selected from the 2D spectrum, in this case, protons 1A and 1B
(Figure 6a); for accuracy, it is important that there is the least possible
amount of overlap with any other absorption. For these peaks (protons
1A and 1B), the integrals are calculated and divided by each other to give
the peak ratio (p/(1 ꢀ p)).
First, the ratio of diagonal peaks and their corresponding cross peaks
in the 2D-EXSY spectrum were plotted against the different mixing
times (τmix) for the different temperatures (Figure 6b). Subsequently, a
curve was fitted for each different temperature using the following
function:
fðT, τmixÞ ¼ pð1 ꢀ exp½k0 expðð ꢀ ΔqG=RÞðð1=TÞ-ð1=T0ÞÞτmixꢂÞ=1
3
ꢀ pð1 ꢀ exp½k0 expðð ꢀ ΔqG=RÞðð1=TÞ ꢀ ð1=T0ÞÞτmixꢂÞ
ð1Þ
In this function, T and τmix represent the different temperatures and
mixing times, respectively. R is the gas constant (8.3 J Kꢀ1 molꢀ1). p
3
3
(population), ΔqG (Gibbs free energy of activation at temperature T0),
and k0 were used as fitting parameters. Subsequently, the rate of
exchange (k) was calculated using the Eyring equation. The notebook
in which the 2D-EXSY calculations were performed was developed by
Dr. E. Otten and Dr. R. Scheek, based on the literature.27
Synthesis of the α-Aryl Ketones 6 and Molecular Motors 4
and 5. 2,3-Dihydro-1H-cyclopenta[a]naphthalen-1-one (7). A solu-
tion of β-chloropropionyl chloride (7.5 mL, 78 mmol) and naphthalene
(10 g, 78 mmol) in 25 mL of carbon disulfide (CS2) under a nitrogen
atmosphere was added over 45 min to anhydrous AlCl3 (13 g, 94 mmol)
in CS2 (100 mL). After 4 h of stirring at room temperature, the carbon
disulfide was removed under reduced pressure to provide a crude oil. To
the residual oil 50 mL of concentrated H2SO4 was added, and the
mixture was heated at 90 °C for 40 min. After being cooled to room
temperature, the mixture was poured onto 200 g of crushed ice and the
reaction mixture was extracted with ether. The combined organic layers
were washed with water, saturated aq NaHCO3, and brine, dried over
Na2SO4, and filtered, and the volatiles were removed in vacuo. The
crude material was purified by flash column chromatography (SiO2,
pentane/EtOAc; 95:5, Rf = 0.64) yielding 7 (11 g, 58 mmol, 74%) as a
white solid: mp 105.0ꢀ105.3 °C; 1H NMR (400 MHz, CDCl3) δ 2.69
(t, J = 5.3 Hz, 2H), 3.07 (t, J = 5.3 Hz, 2H), 7.37 (d, J = 8.2 Hz, 1H), 7.50
(t, J = 7.0 Hz, 1H), 7.62 (t, J = 8.2 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 7.91
(d, J = 8.5 Hz, 1H), 9.11 (d, J = 8.2 Hz, 1H); 13C NMR (101 MHz,
CDCl3) δ 26.0 (CH2), 36.7 (CH2), 123.7 (CH), 123.8 (CH), 126.4
(CH), 127.9 (CH), 128.6 (CH), 129.2 (C), 130.7 (C), 132.4 (C), 135.4
(CH), 158.2 (C), 207.2 (C); HRMS (ESI) m/z calcd. for C13H10O
182.0732, found 182.0735.
General Procedure A for α-Arylation Reaction: 2-(3,5-Dimethylphenyl)-
2,3-dihydro-1H-cyclopenta[a]naphthalen-1-one (6.1). Pd(OAc)2 (0.22 g,
0.96 mmol), t-BuONa (0.46 g, 4.8 mmol), and 2-dicyclohexylphosphino-
20,40,60-triisopropylbiphenyl (0.92 g, 1.9 mmol) were dissolved in toluene
(5 mL) under a nitrogen atmosphere. A solution of ketone 7 (0.42 g,
2.30 mmol) and 1-iodo-3,5-dimethylbenzene (0.33 mL, 1.9 mmol) in toluene
(5 mL) was added. The mixture was stirred and heated at reflux overnight.
After the mixture was cooled to room temperature, water (25 mL) was added,
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FEATURED ARTICLE
2-(4-Methoxyphenyl)-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-
one (6.5). Ketone 6.5 was prepared via general procedure A from ketone
7 (93 mg, 0.51 mmol) and 1-iodo-3-methoxybenzene (100 mg,
0.43 mmol) using Pd(OAc)2 (47.9 mg, 0.21 mmol), t-BuONa (103 mg,
1.07 mmol), and 2-dicyclohexylphosphino-20,40,60-triisopropylbiphenyl
(204 mg, 0.43 mmol). The crude product was purified using flash column
chromatography (SiO2, pentane/EtOAc; 4:1, Rf = 0.47). Ketone 6.5 was
cis-4 (yellow solid): 1H NMR (400 MHz, CDCl3) δ 2.97 (d, J = 15.6
Hz, 1H), 3.86 (dd, J = 15.6, 7.3 Hz, 1H), 4.51 (d, J = 7.1 Hz, 1H), 6.48 (t, J =
7.6 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1H), 7.04 (t, J = 7.5 Hz, 1H), 7.13ꢀ7.21 (m,
5H), 7.38 (d, J = 8.2 Hz, 1H), 7.68ꢀ7.75 (m, 2H); 13C NMR (101 MHz,
CDCl3) δ 42.4 (CH2), 52.9 (CH), 123.2 (CH), 124.4 (CH), 124.5 (CH),
126.1 (CH), 126.7 (CH), 127.2 (CH), 127.9 (CH), 128.5 (CH), 129.1 (C),
129.3 (CH), 132.4 (C), 138.1 (C), 139.0 (C), 144.0 (C), 145.7 (C); HRMS
(ESI) m/z calcd for C38H28 484.2191, found 484.2164.
1
obtained as a pale yellow oil (16.1 mg, 0.056 mmol, 13%): H NMR
(400 MHz, CDCl3) δ 3.33 (dd, J = 17.8, 3.4 Hz, 1H), 3.76 (dd, J = 11.9,
6.0 Hz, 1H), 3.79 (s, 3H), 3.95 (dd, J = 7.9, 3.5 Hz, 1H), 6.87 (d, J = 8.7 Hz,
2H), 7.16 (d, J = 8.7 Hz, 2H), 7.56ꢀ7.61 (m, 2H), 7.67 (t, J = 7.7 Hz,
1H), 7.92 (d, J = 8.5 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 9.14 (d, J = 8.3 Hz,
1H); 13C NMR (101 MHz, CDCl3) δ 36.2 (CH2), 53.0 (CH), 55.3
(CH3), 114.3 (CH), 123.8 (CH), 124.1 (CH), 126.7 (CH), 128.1
(CH), 128.8 (CH), 129.0 (CH), 129.7 (C), 130.1 (C), 132.0 (C), 132.9
(C), 136.1 (CH), 156.9 (C), 158.6 (C), 206.7 (C); HRMS (ESI) m/z
calcd for C20H16O2 289.1223, found 289.1233 (M + H+).
2-(3-((tert-Butyldiphenylsilyloxy)methyl)phenyl)-2,3-dihydro-1H-
cyclopenta[a]naphthalen-1-one (6.7). Ketone 6.7 was prepared via
general procedure A from ketone 7 (0.71 g, 3.93 mmol) and tert-
butyl(3-iodobenzyloxy)diphenylsilane (1.53 g, 3.25 mmol) using Pd-
(OAc)2 (0.36 g, 1.62 mmol), t-BuONa (0.78 g, 8.13 mmol), and
2-dicyclohexylphosphino-20,40,60-triisopropylbiphenyl (1.55 g, 3.25
mmol). The crude product was purified using flash column chroma-
tography (SiO2, pentane/EtOAc; 95:5, Rf = 0.42). Ketone 6.7 was
obtained as a yellow oil (1.09 g, 2.07 mmol, 64%): 1H NMR (400 MHz,
CDCl3) δ 1.07 (s, 9H), 3.36 (dd, J = 17.9, 3.2 Hz, 1H), 3.77 (dd, J =
17.9, 7.9 Hz, 1H), 4.01 (dd, J = 7.9, 3.2 Hz, 1H), 4.79 (s, 2H), 7.19
(s, 1H), 7.32ꢀ7.46 (m, 10H), 7.65ꢀ7.71 (m, 4H), 7.77 (d, J = 7.9 Hz,
2H), 7.95 (d, J = 8.1 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 9.20 (d, J = 8.4 Hz,
1H); 13C NMR (101 MHz, CDCl3) δ 19.20 (C), 26.73 (CH3), 36.22
(CH2), 53.73 (CH), 65.27 (CH2), 123.70 (CH), 124.08 (CH), 124.53
(CH), 124.92 (CH), 126.58 (CH), 126.68 (CH), 127.62 (CH), 127.64
(CH), 128.09 (CH), 128.69 (CH), 129.00 (CH), 129.56 (CH), 129.59
(CH), 129.71 (C), 130.14 (C), 132.86 (C), 133.36 (C), 134.75 (CH),
135.18 (C), 135.48 (CH), 136.11 (CH), 139.94 (C), 141.63 (C), 157.16
(C), 206.42 (C), four (CH) absorptions of aromatic protons were not
observed (overlapping signal); HRMS (ESI) m/z calcd for C36H34O2Si
527.2401, found 527.2425 (M + H+).
2,20-Bis(3-methoxyphenyl)-2,20,3,30-tetrahydro-1,10-bi-
(cyclopenta[a]naphthalenylidene) (5). Molecular motor 5 was
prepared by general procedure B. TiCl4 (0.20 mL, 1.8 mmol) was
added dropwise to a stirred suspension of Zn (0.24 g, 3.6 mmol) in
THF (10 mL) at room temperature. The mixture was heated at reflux
for 2 h in an oil bath. Ketone 6.4 (0.26 g, 0.91 mmol) in THF (5 mL)
was added, and the mixture was stirred overnight at reflux. The mixture
was then cooled, added to 25 mL of a saturated aqueous solution of
NH4Cl, and extracted with Et2O (3 ꢁ 20 mL). The combined organic
layers were washed with brine (2 ꢁ 20 mL), dried over Na2SO4, filtered,
and concentrated in vacuo. Alkene 5 was obtained (85 mg, 0.16 mmol,
35%) as a mixture of trans- and cis-isomers in approximately a 3:2 ratio. A
mixture of trans-5 and cis-5 was purified by chromatography (silica gel;
pentane/EtOAc; 99.5:0.5 to 99:1, no air pressure, Rf -trans = 0.62, Rf -cis =
0.59) to give the trans-5 (50 mg, 0.092 mmol, 21%) and cis-5 (35 mg,
0.064 mmol, 14%).
trans-5 (white solid, appearing as a yellow fluorescent spot on TLC):
1H NMR (400 MHz, CDCl3) δ 2.79 (d, J = 14.9 Hz, 1H), 3.50 (dd, J =
14.9, 6.7 Hz, 1H), 3.61 (s, 3H), 4.26 (d, J = 6.5 Hz, 1H), 6.70 (s, 1H),
6.72 (t, J = 7.9 Hz, 2H), 6.92 (t, J = 7.0 Hz, 1H), 7.10 (t, J = 7.8 Hz, 1H),
7.27 (d, J = 8.9 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H),
7.78 (d, J = 8.5 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H); 13C NMR (101 MHz,
CDCl3) δ 43.3 (CH2), 54.0 (CH), 55.0 (CH3), 111.4 (CH), 113.8
(CH), 120.6 (CH), 123.7 (CH), 124.9 (CH), 125.5 (CH), 127.7 (CH),
128.2 (CH), 128.8 (CH), 129.0 (C), 129.1 (CH), 133.0 (C), 139.4 (C),
140.2 (C), 140.8 (C), 147.1 (C), 159.3 (C); HRMS (ESI) m/z calcd for
C40H33O2 545.2475, found 545.2492.
cis-5 (yellow solid, appearing as a blue fluorescent spot on TLC): 1H
NMR (400 MHz, CDCl3) δ 2.99 (d, J = 15.7 Hz, 1H), 3.63 (s, 3H), 3.86
(dd, J = 15.4, 7.2 Hz, 1H), 4.50 (d, J = 7.2 Hz, 1H), 6.47 (t, J = 7.0 Hz,
1H), 6.68 (dd, J = 8.2, 1.8 Hz, 1H), 6.77 (s, 1H), 6.80 (dd, J = 15.1, 8.5
Hz, 2H), 7.02 (t, J = 7.0 Hz, 1H), 7.09 (t, J = 7.8 Hz, 1H), 7.38 (d, J = 8.1
Hz, 1H), 7.68 (d, J = 8.2 Hz, 1H), 7.72 (d, J = 8.2 Hz, 1H); 13C NMR
(101 MHz, CDCl3) δ 42.4 (CH2), 53.0 (CH), 55.0 (CH3), 111.3 (CH),
113.2 (CH), 119.7 (CH), 123.1 (CH), 124.4 (CH), 124.6 (CH), 126.6
(CH), 127.8 (CH), 129.1 (C), 129.3 (CH), 129.4 (CH), 132.4 (C),
138.1 (C), 138.9 (C), 144.0 (C), 147.3 (C), 159.6 (C); HRMS (ESI)
m/z calcd. for C40H33O2 545.2475, found 545.2483.
General Procedure B for the McMurry Coupling Reaction: 2,20-Bis(3-
phenyl)-2,20,3,30-tetrahydro-1,10-bi(cyclopenta[a]naphthalenylidene)
(4). TiCl4 (0.17 mL, 1.5 mmol) was added dropwise to a stirred
suspension of zinc powder (203 mg, 3.1 mmol) in THF (10 mL) at
room temperature. The mixture was heated at reflux for 2 h in an oil bath.
Ketone 6.3 (200 mg, 0.8 mmol) in THF (5 mL) was added, and the
mixture was stirred overnight at reflux. The mixture was then cooled,
added to 25 mL of a saturated aqueous solution of NH4Cl, and
extracted with Et2O (3 ꢁ 20 mL). The combined organic layers were
washed with brine (2 ꢁ 20 mL), dried over Na2SO4, filtered, and
concentrated in vacuo. Alkene 4 was obtained (31 mg, 0.064 mmol,
16%) as a mixture of trans- and cis-isomers in approximately a 2:1
ratio. A mixture of trans-4 and cis-4 was purified by flash chromatog-
raphy (silica gel; heptane/toluene; 99:1 to 95:5, Rf -trans = 0.21, Rf -cis =
0.14) to give the trans-4 (22 mg, 0.045 mmol, 11%) and cis-5 (9 mg,
0.019 mmol, 5%).
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra for all
S
b
compounds, Eyring plots for the kinetic studies for cis- and trans-5,
and 1H NMR spectra after photochemical and thermal isomerization
experiments for molecular motor cis- and trans-5. This material is
available free of charge via the Internet at http://pubs.acs.org.
trans-4 (pale yellow solid): 1H NMR (400 MHz, CDCl3) δ 2.79 (d,
J = 14.9 Hz, 1H), 3.51 (dd, J = 14.9, 6.6 Hz, 1H), 4.29 (d, J = 6.5 Hz, 1H),
6.87 (t, J = 8.1 Hz, 1H), 7.11ꢀ7.15 (m, 2H), 7.16ꢀ7.21 (m, 3H), 7.27
(d, J = 8.8 Hz, 1H), 7.32ꢀ7.37 (m, 1H), 7.73 (d, J = 8.1 Hz, 2H), 7.84 (d,
J = 8.0 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 43.4 (CH2), 54.1
(CH), 123.7 (CH), 124.9 (CH), 125.4 (CH), 125.8 (CH), 127.8 (CH),
128.09 (CH), 128.13 (CH), 128.2 (CH), 128.7 (CH), 129.0 (C), 133.0
(C), 139.4 (C), 140.3 (C), 140.8 (C), 145.4 (C); HRMS (ESI) m/z
calcd for C38H28 484.2191, found 484.2197.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: b.l.feringa@rug.nl.
’ ACKNOWLEDGMENT
We are grateful to Dr. R. Scheek, Dr. R. Otten, and Ing P. van der
Meulen for helpful suggestions. We acknowledge The Netherlands
8609
dx.doi.org/10.1021/jo201583z |J. Org. Chem. 2011, 76, 8599–8610

The Journal of Organic Chemistry
FEATURED ARTICLE
Organization for Scientific Research (NWO-CW), Zernike Institute
for Advanced Materials, European Research Council (advanced
grant no. 227897, B.L.F.), and the University of Groningen for
financial support.
(18) All of the UVꢀvis and NMR spectroscopic studies were
performed on racemates.
(19) Because of the low rate of thermal inversion from unstable cis-5
to stable cis-5, the solvent was changed from DCM to DCE to allow
temperatures above the boiling point of DCM (40 °C).
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(22) See the Supporting Information for more details.
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(24) This graph shows the region of the spectrum in which the
absorptions are that were used to perform the calculations. These are not
the methoxy protons (proton 4, see Figure 5) and its corresponding
proton (proton 2), but the other two protons (protons 1 and 5) on the
m-methoxyphenyl. The latter were used for the calculations because
their absorptions had less overlap with other absorptions, which is
essential for the accuracy of the calculations.
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