Synthesis of functionalized molecular motors

Article abstract of DOI:10.1055/s-2005-869954

Synthetic routes to two molecular motors are reported. The sterically hindered central olefinic bond connecting the two halves of these C ₂-symmetric molecules was prepared by a McMurry reaction. In this way, a motor with two five-membered rings and a motor with two six-membered rings were prepared, both with two versatile methoxy substituents at positions not interfering with the rotary behavior. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-869954

PAPER
1789
Synthesis of Functionalized Molecular Motors
F
M
unctionalized
M
olecu
a
la
r
Motorstthijs K. J. ter Wiel, Ben L. Feringa*
Department of Organic and Molecular Inorganic Chemistry, Stratingh Institute, University of Groningen, Nijenborgh 4,
747 AG Groningen, The Netherlands
9
Fax +31(50)3634296; E-mail: Feringa@chem.rug.nl.
Received 19 October 2004; revised 7 March 2005
S
Abstract: Synthetic routes to two molecular motors are reported.
The sterically hindered central olefinic bond connecting the two
halves of these C -symmetric molecules was prepared by a McMur-
2
ry reaction. In this way, a motor with two five-membered rings and
a motor with two six-membered rings were prepared, both with two
versatile methoxy substituents at positions not interfering with the
rotary behavior.
MeO
S
1
2
3
Key words: alkenes, arenes, nanostructures, McMurry reactions
Figure 1 The first-generation molecular motor 1, the second gene-
ration molecular motor 2, and the five-membered ring containing mo-
lecular motor 3.
Todays silicon-based computer technology is the result of
six decades of miniaturization of electrical components
11
following a ‘top-down’ approach. However, since limita- ed in the literature. In order to attach these motors onto,
1
tions can be foreseen in the near future, considerable at- for example, a gold surface or to incorporate them into a
tention is being paid to construct functional devices device, they will have to be functionalized in such a way
starting from the smallest components possible, i.e. atoms that their rotary motion is not restricted. Therefore, we
and molecules. This is commonly referred to as the ‘bot- chose to synthesize molecular motors 4 and 5 with a five-
tom-up’ approach in nanotechnology. In recent years nu- and six-membered ring functionalized on the naphthalene
moiety (Figure 2). Since it has been shown that introduc-
tion of a methyl group at the 7- and 7¢-positions of the six-
membered ring containing molecular motors does not in-
terfere with the rotary behavior of the molecule, it was de-
cided to introduce other substituents at this position. For
the five-membered ring motors the same position for
merous devices have been designed and created at the
2
3
4
molecular scale, e.g. molecular motors, muscles, eleva-
5
6
7
tors, scissors, and a processive artificial enzyme. In our
efforts to create functioning molecular machinery, we
have designed molecular motors based on overcrowded
alkenes. Actually, molecule 1 was the first example of a
1
2
unidirectional rotary motor molecule capable of a repeti- functionalization was chosen. A major synthetic problem
tive 360° rotation upon irradiation. The rotation around is the choice of substituents, since a number of reaction
8
the central double bond, functioning as an axis, is gov- conditions used in the synthesis of a motor molecule are
erned by the absolute configuration at the stereogenic cen- rather harsh and the substituent has to be sufficiently ro-
ters. The rotation takes place in four consecutive steps bust to withstand both Friedel–Crafts and McMurry reac-
using light as the source of energy. Each photochemical tions. Therefore the introduction of methoxy substituents
step, fueling the rotary motion, is followed by a thermally into both motors 4 and 5 was envisioned.
induced helix inversion. The direction of rotation is gov-
erned by the methyl substituent attached to the stereogenic
centre adjacent to the central double bond.
OMe
MeO
We have subsequently shown that the direction of rotation
OMe
MeO
9
can be governed by a single stereocentre, present in the
second generation motors 2 and that the rate determining
thermal helix inversion is considerably increased by using
two five-membered rings instead of two six-membered
4
5
1
0
Figure 2 Functionalized molecular motors 4 and 5.
rings as presented in 3 (Figure 1).
A main objective is to construct functional mechanical
nanodevices based on the application of our molecular
motors. Recently, examples of other devices attached to
surfaces or ordered in larger assemblies have been report-
For the molecular motor containing a six-membered ring,
the most convenient way of introducing a methoxy sub-
stituent would be a direct Friedel–Crafts reaction of 2-
methoxynaphthalene with succinic anhydride in a solvent
like nitrobenzene or nitromethane (Scheme 1). This reac-
tion has been described several times. However, under
similar reaction conditions different isomers were report-
SYNTHESIS 2005, No. 11, pp 1789–1796
x
x.
x
x
.
2
0
0
5
Advanced online publication: 20.06.2005
DOI: 10.1055/s-2005-869954; Art ID: T12204SS
Georg Thieme Verlag Stuttgart · New York
©

1
790
M. K. J. ter Wiel, B. L. Feringa
PAPER
1
3
14
ed to be the dominant product. Ghosal reported that the using an AD-column, it was preferred not to perform an
major product of the reaction is the desired isomer 8, in enantioresolution at this stage. A number of synthetic
which substitution has taken place at the 6-position of the steps still had to be performed and the preparative HPLC
naphthalene and not product 7 substituted at the 1-posi- separation of material is time consuming and quite costly.
tion, but our results are more in agreement with those of Deprotection of the ether moieties with BBr could be per-
3
1
3a
Short et al. Indeed, when this reaction was performed, formed quite readily with good yields. The bisphenol 13
most of the product proved to be the result of the substitu- is a useful platform for the attachment of various substit-
tion at the 1-position (7). The desired product 8, substitut- uents. To demonstrate its potential, bisphenol 13 was al-
ed at the 6-position, was obtained only in low yield by lowed to react with 1-pyrenecarbonyl chloride (14),
recrystallization from ethanol. Since this reaction gave prepared from 1-pyrenecarboxylic acid by treatment with
only a poor yield of the desired keto acid, an alternative thionyl chloride, to provide the functionalized motor 15,
route was investigated. Conversion of 2-bromo-6-meth- which was obtained in moderate yield. The reason for the
oxy-naphthalene 9 by reaction with magnesium powder introduction of two pyrene moieties is that their fluores-
1
5
into the Grignard reagent followed by reaction with suc- cence can be used to monitor the rotational behavior. Es-
cinic anhydride gave the keto acid 8 in moderate yield. pecially when 15 has a cis-geometry, the perpendicular
This keto acid 8 can then be converted to the acid 10 using orientation, indicated by molecular mechanics calcula-
classical Huang–Minlon conditions in the Wolff–Kishner tions, of the two pyrene moieties might result in the for-
reduction. Care must be taken not to raise the temperature mation of exciplexes, which can easily be detected. In the
too high, otherwise the methoxy substituent will be UV/Vis spectrum of 15 the absorptions at 356 and 388 nm
cleaved.
can be attributed to the two pyrene moieties.
The acid 10 was then converted to ketone 11 by a ring clo- Although several synthetic routes towards a functional-
sure reaction in polyphosphoric acid (PPA). Methylation ized molecular motor containing two five-membered
of the resulting ketone 11 was performed by deprotona- rings proved to be effective, a route featuring a Wittig–
tion at low temperature with LDA followed by quenching Horner reaction was found to be most efficient. The Wit-
with methyl iodide to provide 12. The ketone could then tig–Horner reagent 16 was readily prepared by an Arbus-
be coupled by a McMurry reaction using TiCl and Zn ov reaction between 2-bromopropionic acid methyl ester
4
1
6
powder as reagents. This gave alkene 4 in 29% yield, ex- and triethylphosphite in high yields. The Wittig–Horner
clusively as the trans isomer. The formation of cis-4 was reagent 16 was treated with NaH in anhydrous DME and
1
7
not observed. Although the enantiomers of methoxy mo- the aldehyde 17 was added, providing the alkene 18 in
tor trans-4 could be separated by analytical chiral HPLC 87% yield. Subsequent hydrogenation using Pd/C in a
O
O
O
O
MeO
OH
+
nitrobenzene
AlCl3, 0 °C, 5%
OH
MeO
O
O
MeO
O
6
7
ratio 10:1
8
a) Mg powder,
Br THF, ∆
O
diethylene glycol, 190 °C
hydrazine, KOH, 61%
OH
OH
O
b) succinic anhydride,
°C, 35%
MeO
O
MeO
0
MeO
9
8
10
a) LDA, THF, –60 °C
b) MeI, 98%
TiCl4, Zn
BBr3, CH2Cl2
0 °C, 97%
PPA, 110 °C
8%
OMe
MeO
4
THF, 29%
O
O
MeO
MeO
11
12
4
O
Cl
O
OH
O
HO
14
O
O
CH2Cl2, Et3N, 73%
13
1
5
Scheme 1 Synthesis of the functionalized racemic molecular motor 4 containing two six-membered rings and of the bispyrene functionalized
molecular motor 15.
Synthesis 2005, No. 11, 1789–1796 © Thieme Stuttgart · New York

PAPER
Functionalized Molecular Motors
1791
mixture of ethanol and ethyl acetate provided ester 19 in good results were obtained and the methyl moiety could
near quantitative yield. Hydrolysis to the acid 20 was be cleaved to provide naphthol 22 in 77% yield. The ionic
achieved using LiOH in a mixture of water and methanol liquid used was prepared easily by mixing AlCl and
3
at room temperature. Acid 20 was subsequently converted Me N·HCl in CH Cl followed by evaporation of the sol-
3
2
2
to ketone 21 using standard Friedel–Crafts reaction condi- vent after stirring for two hours at room temperature. Al-
tions in excellent yield. Two of these ketones were then though cleavage could be performed according to the
reductively coupled following a McMurry protocol with described conditions, the reaction was relatively slow and
TiCl and Zn powder to provide the alkene 5 as a cis-trans was therefore performed at 80 °C overnight. The resulting
4
mixture in a ratio of approximately 1:1. Contrary to the naphthol 22 was then efficiently protected as the TBDMS
motor 4, comprising two six-membered rings, both cis-5 ether using DMAP in CH Cl to yield 23. Coupling of the
2
2
and trans-5 were obtained. Unlike their unsubstituted ketones using the McMurry protocol resulted in a cis-
counterparts, the methoxy-substituted cis- and trans-iso- trans mixture of the protected molecular motor 24 in a ra-
mers of 5 could be separated readily by column chroma- tio of approximately 2:1 in a total yield of 90%. By recrys-
tography and were obtained in 16% (cis-5) and 18% tallization from ethanol, pure cis-24 could be obtained.
(
trans-5) yield, respectively. However, various attempts TBDMS-protected molecular motor 24 was prepared,
to cleave the two ether functionalities resulted in either starting from 6-bromo-2-naphthol in a combined yield of
decomposition or recovery of the motor molecule. Since 30% over nine consecutive steps. Reaction with TBAF in
it proved not to be feasible to deprotect the methoxy func- THF at room temperature gave complete conversion to the
tionality at this stage, it was decided to introduce another bisphenol 25 within ten minutes. This bisphenol 25 can be
functionality that can be cleaved off under milder reaction used as a scaffold for the introduction of various substitu-
conditions.
ents such as two fluorescent pyrene-moieties as used for
the six-membered ring containing motor 15 depicted in
Scheme 3. It might also be possible to resolve the phenol
by attaching chiral auxiliaries to allow the separation of
the two isomers.
Although the use of various protecting groups was inves-
tigated, major attention was focused on the deprotection
of the methoxy group in 21. For the deprotection of aro-
matic methyl ethers, reagents like BBr and HBr are nor-
3
mally used. However, previously performed reactions In conclusion, in the present paper we have described gen-
with similar molecules resulted in poor yields or difficult eral synthetic routes to molecular motors with appropriate
workup procedures were needed. Using simple ionic liq- functionalities to construct more elaborate systems with-
uid methodology, recently reported in the literature,18 out interfering with the motor function.
a) NaH, DME, 0 °C
O
P
CO2Me
CO2Me
H2, Pd/C, r.t.
LiOH, MeOH,
EtO
EtO
CO2Me b)
MeO
O
EtOH / EtOAc, 99%
2
H O, r.t., 91%
MeO
MeO
1
6
19
18
17, 87%
a) SOCl2, DMF, CH2Cl2
b) AlCl3, toluene,
CO2H
TiCl , Zn
4
MeO
MeO
MeO
OMe
MeO
O
THF, ∆
0
°C, 91%
MeO
20
21
trans-5, 18%
cis-5, 16%
Scheme 2 Synthesis of molecular motor 5 containing in each half of the molecule a five-membered ring.
Me3NH·HCl,
TBDMSCl, DMAP
r.t., CH2Cl2, 79%
TiCl4, Zn
O
O
AlCl3, 80 °C, 77%
O
Si
THF, ∆, 90%
O
MeO
21
HO
22
23
Si
Si
Si
TBAF, THF
95%
HO
HO
O
O
O
O
Si
ratio 1:2
trans-24
cis-24
cis-25
Scheme 3 Synthesis of molecular motor 25 ready for further functionalization.
Synthesis 2005, No. 11, 1789–1796 © Thieme Stuttgart · New York

1
792
M. K. J. ter Wiel, B. L. Feringa
PAPER
1
The high-resolution one- and two-dimensional H NMR spectra
were obtained using a Varian Gemini-200, Varian VXR-300, Vari-
7,7¢-Dimethoxy-2,2¢-dimethyl-2,2¢,3,3¢-tetrahydro-1,1¢-bicyclo-
penta[a]naphthalenylidene (5)
an Mercury Plus and a Varian Unity Plus Varian-500 operating at
1
To a stirred suspension of Zn powder (1.01 g, 15.4 mmol) in THF
99.97, 299.97, 399.93, and 499.86 MHz, respectively. 1 C NMR
3
(8 mL), TiCl (0.849 mL, 1.46 g, 7.70 mmol) was added carefully
4
spectra were recorded on a Varian Gemini-200, Varian VXR-300,
Varian Mercury Plus, and a Varian Unity Plus Varian-500 operating
at 50.29, 75.43, 100.57, and 125.70 MHz, respectively. Chemical
shifts are reported in d units (ppm) relative to the residual deuterated
at 0 °C. The dark mixture was then refluxed for 90 min and ketone
21 (0.800 g, 3.54 mmol), was added in a small amount of THF (2
mL). The mixture was subsequently heated at reflux for 18 h and
then poured into a sat. aq soln of NH Cl (100 mL) and extracted
4
1
13
solvent signals of CHCl ( H NMR: d 7.26 ppm; C NMR: d 77.0
with EtOAc (3 × 100 mL). Drying of the combined organic layers
and evaporation of all volatiles gave a yellow oil containing a small
amount of starting material and the cis and trans isomers of the ole-
fin 5. The reaction mixture was purified by column chromatography
(heptane–EtOAc, 50: 1) giving both the trans olefin 5 (130 mg,
0.310 mmol, 18%) and cis olefin (120 mg, 0.286 mmol, 16%) as
yellow solids.
3
1
13
ppm); DMSO ( H NMR: d 2.49; C NMR: d 39.5 ppm), benzene
1
13
1
(
H NMR: d 7.15 ppm; C NMR: d 128.0 ppm) and toluene ( H
31
NMR: d 2.08 ppm) or relative to an external standard for P NMR
(
NPCl ) at d 19.91 ppm in CDCl . Melting points were taken on a
2
3
3
Mettler FP-2 melting point apparatus, equipped with a Mettler FP-
1 microscope. Optical rotations were measured with a Perkin Elm-
2
er 241 Polarimeter. UV/Vis measurements were performed on a
Hewlett-Packard HP 8453 FT spectrophotometer using Uvasol
grade solvents (Merck). MS (EI) and HRMS (EI) spectra were ob-
tained with a Jeol JMS-600 spectrometer. Elemental analyses were
performed in the microanalytical department with a Foss-Heraeus
CHN-O-Rapid or a EuroVector Euro EA Elemental Analyzer. The
average value of duplo measurements are reported. Column chro-
matography was performed on silica gel (Aldrich 60, 230–400
mesh). HPLC analyses were performed on Shimadzu HPLC system
equipped with two LC-10ADvp solvent delivery systems, a DGU-
trans-5
Rf 0.26.
1
H NMR (300 MHz, CDCl ): d = 1.29 (d, J = 6.2 Hz, 6 H), 2.31 (d,
3
J = 14.6 Hz, 2 H), 2.93 (dd, J = 14.6, 5.5 Hz, 2 H), 3.00–3.08 (m, 2
H), 3.97 (s, 6 H), 7.19–7.22 (m, 4 H), 7.36 (d, J = 8.1 Hz, 2 H), 7.65
(
d, J = 8.1 Hz, 2 H), 8.16 (d, J = 9.9 Hz, 2 H).
1
3
C NMR (75 MHz, CDCl ): d = 19.4 (q), 41.0 (t), 43.0 (d), 55.2 (q),
3
1
06.4 (d), 117.7 (d), 124.6 (d), 125.8 (s), 126.5 (d), 128.2 (d), 134.1
(
s), 138.6 (s), 139.4 (s), 141.5 (s), 156.7 (s).
1
4A degasser, a SIL-10ADvp autosampler, a SPD-M10A UV/Vis
photodiode array detector, a CTO-10Avp column oven and a SCL-
0Avp controller unit using Chiralcel OD (Daicel), Chiralcel AD
Daicel), (R,R)-Whelk 01 (Regis) and Chiralcel OB-H (Daicel) col-
cis-5
1
(
Yellow solid; 190.9–191.8 °C; R 0.17.
f
umns. Chemicals were used as received from Acros, Aldrich, Fluka,
or Merck.
1
H NMR (400 MHz, CDCl ): d = 1.19 (d, J = 6.6 Hz, 6 H), 2.64 (d,
3
J = 14.3 Hz, 2 H), 3.51–3.59 (m, 4 H), 3.74 (s, 6 H), 6.10 (dd, J =
9
.2, 2.6 Hz, 2 H), 6.54 (d, J = 9.2 Hz, 2 H), 6.99 (d, J = 2.6 Hz, 2
*
*
*
*
(
1
3R ,3¢R )-(P ,P )-trans-7,7¢-Dimethoxy-3,3¢-dimethyl-
,1¢,2,2¢,3,3¢,4,4¢¢-tetrahydrobiphenanthrenylidene (4)
A mixture of Zn powder (0.706 g, 10.8 mmol) and TiCl (0.605 mL,
H), 7.44 (d, J = 8.1 Hz, 2 H), 7.59 (d, J = 8.1 Hz, 2 H).
1
3
C NMR (75 MHz, CDCl ): d = 20.7 (q), 40.4 (t), 42.2 (d), 55.0 (q),
3
4
1
06.1 (d), 116.6 (d), 124.0 (d), 125.3 (s), 127.3 (d), 128.0 (d), 133.4
1
.04 g, 5.48 mmol) in THF (3 mL) was refluxed for 90 min. To this
black mixture was added ketone 12 (640 mg, 2.67 mmol) in THF (2
mL). Subsequently, the reaction mixture was refluxed for 44 h.
(
s), 136.9 (s), 140.0 (s), 141.8 (s), 156.1 (s).
+
MS (EI): m/z (%) = 420 (M , 100).
Quenching with a sat. aq soln of NH Cl (100 mL) and extraction
4
HRMS (EI): m/z calcd for C H O : 420.2089; found: 420.2108.
3
0
28
2
with EtOAc (3 × 100 mL) gave after drying (MgSO ) and removal
4
of the organic solvents a brown oil, which was purified by column
4
-(6-Methoxynaphthalen-2-yl)-4-oxobutyric Acid (8) and 4-(2-
chromatography (SiO , heptane–EtOAc, 16:1, R 0.55). The desired
2
f
Methoxynaphthalen-1-yl)-4-oxobutyric Acid (7)
compound 4 was obtained as a slighly colored oil, which under high
vacuum turned to a colorless, fluffy solid (176 mg, 0.393 mmol,
A mixture of these compounds was obtained following the literature
13a
procedure.
Alternatively, 6-bromo-2-methoxynaphthalene (9;
2
9%).
2
0.0 g, 84.4 mmol) was converted to the Grignard reagent. Naph-
1
H NMR (300 MHz, CDCl ): d = 0.78 (d, J = 6.6 Hz, 6 H), 1.23–
thyl compound 9 (1 g) was added to THF (5 mL) and this was added
to a suspension of Mg powder (2.65 g, 109 mmol) in THF (15 mL)
containing a small crystal of iodine. This mixture was heated gently
for 5 min until the Grignard reaction had started. The remaining 9
(19 g) was added in THF (150 mL). After the addition was com-
plete, the mixture was heated at reflux for 2 h. The reaction mixture
was cooled to 0 °C, then succinic anhydride (12.0 g, 120 mmol) was
added and the resulting solution was stirred overnight. Acidification
3
1
.28 (m, 2 H), 1.82–1.91 (m, 2 H), 2.64–2.73 (m, 6 H), 3.97 (s, 6 H),
7
2
.21–7.30 (m, 6 H), 7.65 (d, J = 8.1 Hz, 2 H), 8.33 (d, J = 9.2 Hz,
H).
1
3
C NMR (75 MHz, CDCl ): d = 18.6 (q), 27.1 (t), 31.2 (t), 33.7 (d),
3
5
5.2 (q), 106.2 (d), 118.2 (d), 125.2 (d), 127.1 (d), 127.4 (d), 127.8
(
s), 133.3 (s), 134.2 (s), 134.8 (s), 136.4 (s), 156.8 (s);
+
+
MS (EI): m/z (%) = 449 (M , 12), 448 (M , 100).
with an aq soln of HCl (1 N; 500 mL), extraction with Et O (3 × 500
2
mL), and drying (MgSO ) gave a brown oil. To this oil was added a
HRMS (EI): m/z calcd for C H O : 448.2402; found: 448.2400.
4
3
2
32
2
small quantity of Et O (50 mL) from which the desired product 8
2
UV/Vis (n-hexane): l (e) = 234 (72800), 304 (12900), 327 (9300),
36 (9700), 342 (11800).
precipitated as a white solid (7.84 g, 30.4 mmol, 36%). The 1,2-iso-
mer 7 was obtained by the Friedel–Crafts reaction.
3
The enantiomers of trans-4 were resolved by chiral HPLC using a
Daicel Chiralcel AD column as the stationary phase and a mixture
1,2-Isomer 7
–
1
13a
of heptane–i-PrOH (95:5) as the eluent at a rate of 1 mL min giv-
ing two fractions (first fraction: t 3.84 min; second fraction t 5.61
White solid; mp 133.5–136.5 °C (lit. 136.5–137.5 °C).
R
R
1
H NMR (300 MHz, CDCl ): d = 2.88 (t, J = 6.6 Hz, 2 H), 3.29 (t,
3
min).
J = 6.6 Hz, 2 H), 3.96 (s, 3 H), 7.28 (d, 9.0 Hz, 1 H), 7.33–7.37 (m,
1
H), 7.44–7.49 (m, 1 H), 7.73 (d, J = 8.4 Hz, 1 H), 7.79 (d, J = 8.1
Hz, 1 H), 7.90 (d, J = 9.0 Hz, 1 H).
Synthesis 2005, No. 11, 1789–1796 © Thieme Stuttgart · New York

PAPER
Functionalized Molecular Motors
1793
1
3
+
C NMR (75 MHz, CDCl ): d = 28.1 (t), 39.3 (t), 56.4 (q), 112.6
MS (EI): m/z (%) = 244 (M , 34), 171 (100), 128 (89).
3
(
1
d), 123.6 (d), 124.1 (d), 127.7 (d), 128.0 (d), 128.8 (2 s), 130.5 (s),
31.6 (d), 153.7 (s), 178.9 (s), 205.1 (s).
HRMS (EI): m/z calcd for C H O : 244.1100; found: 244.1093.
1
5
16
3
+
MS (EI): m/z (%) = 258 (M , 25), 185 (100).
7-Methoxy-2,3-dihydro-4(1H)-phenanthrenone (11)
PPA (50 mL) was heated to 60 °C and the acid 10 (2.49 g, 10.2
mmol) was added. Stirring was continued for 3 h at 110 °C. The re-
action mixture was then poured into ice-water (200 mL) and after
HRMS (EI): m/z calcd for C H O : 258.0892, found: 258.0895.
1
5
14
4
2
,6-Isomer 8
1
3a
hydrolysis overnight the mixture was extracted with Et O (3 × 100
2
White solid; mp 147.4–148.5 °C (lit. 148.5–149 °C).
mL). Drying of the combined organic layers (MgSO ) and removal
4
1
H NMR (300 MHz, CDCl ): d = 2.80 (t, J = 6.6 Hz, 2 H), 3.37 (t,
3
of the volatiles under reduced pressure gave a brown oil which was
J = 6.6 Hz, 2 H), 3.89 (s, 3 H), 7.10 (s, 1 H), 7.14 (dd, J = 8.8, 2.6
Hz, 1 H), 7.72 (d, J = 8.8 Hz, 1 H), 7.80 (d, J = 8.8 Hz, 1 H), 7.96
purified by column chromatography (SiO ; hexane–EtOAc, 16:1; Rf
2
0
.37) resulting in a slightly yellow oil (1.10 g, 4.87 mmol, 48%).
(
d, J = 8.4 Hz, 1 H), 8.38 (s, 1 H).
1
H NMR (300 MHz, CDCl ): d = 2.13–2.21 (m, 2 H), 2.76 (t, J =
3
1
H NMR (300 MHz, DMSO-d ): d = 2.62 (t, J = 6.0 Hz, 2 H), 3.34
6
6.6 Hz, 2 H), 3.07 (t, J = 6.0 Hz, 2 H), 3.91 (s, 3 H), 7.11 (d, J = 2.6
Hz, 1 H), 7.25–7.29 (m, 2 H), 7.81 (d, J = 8.4 Hz, 1 H), 9.34 (d, J =
(
t, J = 6.0 Hz, 2 H), 3.89 (s, 3 H), 7.24 (dd, J = 8.8, 1.8 Hz, 1 H),
7
8
.39 (d, J = 1.5 Hz, 1 H), 7.91 (m, 2 H), 8.03 (d, J = 8.8 Hz, 1 H),
.60 (s, 1 H).
9
.5 Hz, 1 H).
1
3
C NMR (75 MHz, CDCl ): d = 22.8 (t), 30.9 (t), 40.8 (t), 54.8 (q),
3
1
3
C NMR (75 MHz, DMSO-d ): d = 28.1 (t), 33.0 (t), 55.5 (q), 106.1
6
106.4 (d), 120.2 (d), 126.3 (s), 126.8 (s), 127.2 (d), 128.0 (d), 132.8
(
d), 119.6 (d), 124.2 (d), 127.1 (d), 127.5 (s), 129.8 (d), 131.4 (d),
(
d), 134.0 (s), 144.1 (s), 156.8 (s), 200.3 (s).
1
31.8 (s) 137.0 (s), 159.4 (s), 174.1 (s), 198.1 (s).
+
MS (EI): m/z (%) = 226 (M , 100), 198 (30), 170 (43).
+
MS (EI): m/z (%) = 258 (M , 38), 185 (100).
HRMS (EI): m/z calcd for C H O : 226.0994; found: 226.0995.
1
5
14
2
HRMS (EI): m/z calcd for C H O : 258.0892; found: 258.0892.
1
5
14
4
7
-Methoxy-3-methyl-2,3-dihydro-4(1H)-phenanthrenone (12)
2
-Bromo-6-methoxynaphthalene (9)
To a solution of LDA (3.20 mmol) in THF (10 mL) was added ke-
tone 11 (0.651 g, 2.88 mmol) at –60 °C. The solution turned red rap-
idly after addition of the ketone. After stirring for 1 h at –60 °C, MeI
(0.500 mL, 1.14 g, 8.03 mmol) was added and the reaction mixture
turned brownish. The temperature of the reaction mixture was al-
lowed to reach r.t. overnight, the reaction mixture was quenched
with a sat. aq soln of NH Cl (50 mL), extracted with Et O (3 × 50
mL), and dried over MgSO . After removal of the organic volatiles
under reduced pressure, the impure compound 12 was obtained as a
brown oil, which was purified by column chromatography (SiO2;
heptane–EtOAc, 16:1, R 0.36) yielding a colorless oil (0.679 g,
2
0
A suspension of 6-bromo-2-naphthol (18.4 g, 82.5 mmol), K CO
2
3
(20.0 g, 145 mmol), and MeI (10.0 mL, 22.8 g, 160 mmol) was
stirred overnight in DMF (100 mL). Addition of Et O (300 mL),
2
thorough washing with H O (8 × 200 mL), drying over MgSO , and
2
4
subsequent removal of the organic volatiles gave 9 as a white solid
18.7 g, 78.9 mmol, 96%).
(
4
2
Mp 111.6–111.8 °C (lit.21 108 °C).
4
1
H NMR (300 MHz, CDCl ): d = 3.92 (s, 3 H), 7.10 (d, J = 2.2 Hz,
3
1
H), 7.16 (dd, J = 8.8, 2.6 Hz, 1 H), 7.52 (d, J = 8.1 Hz, 1 H), 7.63
f
(
m, 2 H), 7.92 (d, J = 1.5 Hz, 1 H).
2
.83 mmol, 98%).
1
3
C NMR (75 MHz, CDCl ): d = 55.3 (q), 105.7 (d), 117.0 (s), 119.7
1
3
H NMR (300 MHz, CDCl ): d = 1.29 (d, J = 6.6 Hz, 3 H), 1.88–
3
(
d), 128.3 (d), 128.4 (d), 129.55 (d), 129.6 (d), 130.0 (s), 133.0 (s),
2
.05 (m, 1 H), 2.19–2.28 (m, 1 H), 2.67–2.77 (m, 1 H), 3.03–3.23
1
57.8 (s).
MS (EI): m/z (%) = 238 (M , 100), 236 (M , 100), 195 (45), 193
47).
HRMS (EI): m/z calcd for C H981BrO: 235.9836; found: 235.9847.
(
m, 2 H), 3.90 (s, 3 H), 7.10 (d, J = 2.9 Hz, 1 H), 7.23–7.35 (m, 2
+
+
H), 7.79 (d, J = 8.4 Hz, 1 H), 9.27 (d, J = 9.5 Hz, 1 H).
13
(
C NMR (75 MHz, CDCl ): d = 15.8 (q), 29.9 (t), 31.2 (t), 43.7 (d),
3
1
1
55.0 (q), 106.6 (d), 120.2 (d), 126.5 (s), 127.1 (s), 127.3 (d), 128.0
(
d), 132.6 (d), 134.1 (s), 143.4 (s), 157.0 (s), 203.4 (s).
4
-(6-Methoxynaphthalen-2-yl)butyric Acid (10)
The keto acid 8 (7.40 g, 287 mmol) was mixed with KOH (8.00 g,
43 mmol), hydrazine monohydrate (5.00 mL, 5.10 g, 102 mmol),
+
MS (EI): m/z (%) = 240 (M , 100), 198 (59), 170 (73).
HRMS (EI): m/z calcd for C H O : 240.1150; found: 240.1160.
1
16 16
2
and H O (4.5 mL) in diethylene glycol (60 mL). The mixture was
heated initially for 3 h at 120 °C and then for a further 3 h at 190 °C.
The dark brown mixture was then cooled to r.t. and acidified with
2
*
*
*
*
(
3R ,3¢R )-(P ,P )-trans-(±)-1,1¢,2,2¢,3,3¢,4,4¢-Octahydro-7,7¢-di-
hydroxy-3,3¢-dimethyl-4,4¢-biphenanthrylidene (13)
Motor 4 (55.0 mg, 0.123 mmol) was dissolved in CH Cl (5 mL).
an aq soln of HCl (10%; 100 mL). H O (200 mL) was added and the
2
2
2
After cooling to 0 °C, BBr (0.100 mL, 0.377 g, 0.151 mmol) was
added and the temperature of the reaction mixture was allowed to
reach r.t. overnight. Additional CH Cl (50 mL) was added and the
organic layer was washed with brine (3 × 50 mL). Drying (MgSO )
and evaporation of the solvent gave the bisphenol 13 as a slightly
yellow solid (50.0 mg, 0.119 mmol, 97%).
mixture was extracted with Et O (3 × 200 mL). The combined or-
3
2
ganic layers were washed with H O (4 × 200 mL), dried (MgSO ),
2
4
and then all volatiles were removed in vacuo giving 10 as a slightly
2
2
brown oil, that crystallized upon standing (4.29 g, 17.6 mmol,
4
6
1%).
Mp 161.5–164.8 °C (lit.19 166–168 °C).
1
H NMR (300 MHz, CDCl ): d = 0.78 (d, J = 6.6 Hz, 6 H), 1.23–
.28 (m, 2 H), 1.82–1.91 (m, 2 H), 2.66–2.73 (m, 6 H), 7.16–7.29
m, 6 H), 7.59 (d, J = 8.1 Hz, 2 H), 8.33 (d, J = 8.8 Hz, 2 H).
1
3
H NMR (300 MHz, CDCl ): d = 1.99–2.09 (m, 2 H), 2.41 (t, J =
3
1
(
7
2
.5 Hz, 2 H), 2.81 (t, J = 7.5 Hz, 2 H), 3.91 (s, 3 H), 7.11–7.24 (m,
H), 7.30 (dd, J = 8.4, 1.5 Hz, 1 H), 7.55 (s, 1 H), 7.68 (d, J = 8.8
1
3
C NMR (75 MHz, CDCl ): d = 18.5 (q), 27.1 (t), 31.2 (t), 33.8 (d),
09.9 (d), 117.3 (d), 124.8 (d), 127.3 (d), 127.7 (s), 127.8 (d), 133.3
s), 134.2 (s), 134.8 (s), 136.5 (s), 152.5 (s).
Hz, 2 H).
3
1
(
1
3
C NMR (75 MHz, CDCl ): d = 26.1 (t), 33.2 (t), 34.8 (t), 55.1 (q),
3
1
05.5 (d), 118.6 (d), 126.3 (d), 126.7 (d), 127.6 (d), 128.8 (d), 128.9
+
MS (EI): m/z (%) = 420 (M , 100).
(
s), 128.9 (s), 133.0 (s), 136.2 (s), 157.1 (s), 179.7 (s).
HRMS (EI): m/z calcd for C H O : 420.2089; found: 420.2100.
3
0
28
2
Synthesis 2005, No. 11, 1789–1796 © Thieme Stuttgart · New York

1
794
M. K. J. ter Wiel, B. L. Feringa
PAPER
Pyrene-1-carbonyl Chloride (14)
r.t., a solution of aldehyde 17 (300 mg, 1.61 mmol) in DME (5 mL)
was added. Immediately, the suspension became a clear solution
while a sticky material precipitated. Stirring was continued for 1 h
A suspension of 1-pyrenecarboxylic acid (100 mg, 0.407 mmol)
was refluxed for 1 h in CH Cl (20 mL) in the presence of SOCl
2
2
2
(
0.500 mL, 0.815 g, 6.85 mmol) and a drop of DMF. The organic
at r.t. To the reaction mixture was then added a sat. aq soln of NH Cl
4
volatiles were then removed under reduced pressure yielding a yel-
low solid which was used directly in subsequent reactions.
(50 mL), followed by extraction with Et O (3 × 40 mL). Drying
2
(Na SO ) and evaporation of all volatiles gave a yellow solid, which
2
4
1
was purified by flash column chromatography (SiO ; heptane–
2
H NMR (300 MHz, CDCl ): d = 8.06–8.32 (m, 7 H), 8.91 (d, J =
3
EtOAc, 4:1) giving a white solid (360 mg, 1.41 mmol, 87%). Alter-
natively, the product can be recrystallized from a mixture of
EtOAc–EtOH giving white crystals.
8
.1 Hz, 1 H), 9.04 (d, J = 9.5 Hz, 1 H).
*
*
*
*
(
3R ,3¢R )-(P ,P )-trans-(±)-1,1¢,2,2¢,3,3¢,4,4¢-Octahydro-7,7¢-[(1-
pyrenylcarbonyl)oxy]-3,3¢-dimethyl-4,4¢-biphenanthrylidene
15)
Mp 109.0–110.4 °C.
(
1
H NMR (300 MHz, CDCl ): d = 2.22 (s, 3 H), 3.84 (s, 3 H), 3.94
3
The acid chloride 14 (100 mg, 0.407 mmol) was added to a solution
of bisphenol 13 (50.0 mg, 0.119 mmol) in CH Cl (10 mL) in the
presence of Et N (0.500 mL, 0.360 g, 3.56 mmol). After stirring for
1
quenched with a sat. soln of NH Cl (100 mL) and extracted with
CH Cl (50 mL). The organic layer was then washed with an aq soln
of HCl (1 N; 2 × 50 mL), NaOH (1 N; 50 mL), and brine (2 × 50
mL). After drying (MgSO ), the volatiles were removed in vacuo
(
(
1
s, 3 H), 7.14–7.19 (m, 2 H), 7.50 (d, J = 8.4 Hz, 1 H), 7.73–7.82
2
2
m, 4 H).
3
3
C NMR (75 MHz, CDCl ): d = 14.1 (q), 51.9 (q), 55.1 (q), 105.5
h at 0 °C and then at r.t. for 90 min the reaction mixture was
3
(
d), 119.1 (d), 126.6 (d), 127.3 (s), 127.5 (d), 128.4 (s), 129.3 (d),
4
1
29.7 (d), 131.0 (s), 134.1 (s), 139.0 (d), 158.3 (s), 169.1 (s).
2
2
+
MS (EI): m/z (%) = 256 (M , 100).
4
HRMS (EI): m/z calcd for C H O : 256.1099; found: 256.1102.
1
6
16
3
and the residue was purified by column chromatography (SiO , hep-
2
tane–EtOAc, 4:1; R 0.22) and obtained as a slightly yellow solid
Anal. Calcd for C16H O : C, 75.0; H, 6.29. Found: C, 74.5; H, 6.26.
16 3
f
(
77.0 mg, 880 mmol, 73%).
3
-(6-Methoxynaphthalen-2-yl)-2-methylpropionic Acid Methyl
Mp >200 °C.
Ester (19)
1
H NMR (500 MHz, CDCl ): d = 0.89 (d, J = 6.8 Hz, 6 H), 1.36–
3
Unsaturated ester 18 (1.95 g, 7.62 mmol) was dissolved in a mixture
of EtOH (50 mL) and EtOAc (50 mL) and stirred overnight under
hydrogen at atmospheric pressure at r.t. in the presence of Pd/C (100
mg, 10%). After filtration, the organic volatiles were removed giv-
ing the desired saturated ester 19 as a colorless oil (2.95 g, 7.56
mmol, 99%) which solidified upon standing.
1
.39 (m, 2 H), 1.94–2.00 (m, 2 H), 2.81–2.84 (m, 6 H), 7.40 (d, J =
.1 Hz, 2 H), 7.61 (dd, J = 9.1, 2.2 Hz, 2 H), 7.81 (d, J = 8.8 Hz, 2
8
H), 7.90 (d, J = 2.0 Hz, 2 H), 8.08–8.13 (m, 2 H), 8.16 (d, J = 8.8
Hz, 2 H), 8.25 (d, J = 9.3 Hz, 2 H), 8.29–8.38 (m, 8H), 8.59 (d, J =
9
.3 Hz, 2 H), 9.00 (d, J = 8.3 Hz, 2 H), 9.47 (d, J = 9.8 Hz, 2 H).
1
3
C NMR (75 Hz, CDCl ): d = 18.5 (q), 27.3 (t), 31.2 (t), 33.9 (d),
3
Mp 54.6–56.8 °C.
1
(
1
1
19.3 (d), 121.1 (d), 122.3 (s), 124.2 (s), 124.3 (d), 124.9 (d), 125.0
1
H NMR (300 MHz, CDCl ): d = 1.18 (d, J = 6.6 Hz, 3 H), 2.75–
3
s), 126.3 (d), 126.4 (d), 126.5 (d), 126.6 (d), 127.2 (d), 127.5 (d),
29.1 (d), 130.0 (d), 130.1 (d), 130.39 (s), 130.42 (s), 131.0 (s),
32.0 (s), 132.9 (s), 134.8 (s), 135.0 (s), 136.4 (s), 136.7 (s), 148.1
2
7
7
.86 (m, 2 H), 3.12–3.19 (m, 1 H), 3.64 (s, 3 H), 3.91 (s, 3 H), 7.11–
.15 (m, 2 H), 7.27 (dd, J = 8.4, 2.6 Hz, 1 H), 7.54 (s, 1 H), 7.65–
.69 (m, 2 H).
(s), 166.6 (s); one (d) was not observed.
13C NMR (75 MHz, CDCl
4.8 (q), 105.3 (d), 118.5 (d), 126.6 (d), 126.9 (d), 127.6 (d), 128.7
d), 133.0 (s), 134.2 (s), 157.1 (s), 176.2 (s), one (s) was not ob-
served.
): d = 16.5 (q), 39.4 (t), 41.1 (d), 51.2 (q),
+
3
MS (DI): m/z (%) = 876 (M , 5), 648 (2), 420 (4), 229 (100), 201
(
5
(
46).
It was impossible to acquire an exact mass of this compound. We
attempted to separate the enantiomers of this compound, but neither
of the chiral HPLC (OD, AD, AS, OJ, Whelk) columns tried gave
any resolution.
+
MS (EI): m/z (%) = 258 (M , 36), 171 (100).
HRMS (EI): m/z calcd for C16 : 258.1256; found: 258.1251.
Anal. Calcd for C16 : C, 74.4; H, 7.0. Found: C, 74.5; H, 7.0.
H O
18 3
UV/Vis: (CH Cl ): l
(
(e) = 275 (18800), 285 (24900), 356
H O
18 3
2
2
max
22400), 388 (9900).
3
-(6-Methoxynaphthalen-2-yl)-2-methylpropionic Acid (20)
Ester 19 (0.910 g, 3.53 mmol) was stirred overnight in a mixture of
LiOH (1.00 g, 41.7 mmol), methanol (5 mL) and H O (15 mL). Af-
ter acidification with an aq soln of HCl (10%), the mixture was ex-
tracted with Et
2
-(Diethoxyphosphoryl)propionic Acid Methyl Ester (16)
This compound was prepared according to a procedure reported in
2
the literature16 and was obtained as a colorless liquid.
1
2
O (2 × 50 mL). The ether layers were washed with
H NMR (300 MHz, CDCl ): d = 1.31–1.35 (m, 6 H), 1.44 (dd, J =
3
brine (2 × 50 mL), dried over MgSO , and then all the volatiles were
4
1
4
8.0, 7.0 Hz, 3 H), 2.99–3.09 (m, 1 H), 3.75 (s, 3 H), 4.10–4.20 (m,
H).
removed to give acid 20 as a white solid (0.781 g, 3.20 mmol, 91%).
1
3
2
Mp 137.9–139.4 °C.
1H NMR (300 MHz, CDCl
2.88 (m, 2 H), 3.17–3.22 (m, 1 H), 3.91 (s, 3 H), 7.11–7.14 (m, 2 H),
7.26–7.30 (m, 1 H), 7.56 (s, 1 H), 7.66–7.69 (m, 2 H).
C NMR (75 MHz, CDCl ): d = 11.1 (dq, J = 6.1 Hz), 15.7 (dd,
3
3
PC
3J = 2.5 Hz), 15.8 (dd, J = 2.5 Hz), 38.1 (dd, J = 133 Hz),
5
1
): d = 1.21 (d, J = 6.6 Hz, 3 H), 2.77–
PC
PC
PC
3
2
2
1.8 (q), 61.1 (dt, J = 7.3 Hz), 169.5 (d, J = 4.9 Hz).
1
PC
PC
3
P NMR (81 MHz, CDCl ): d = 22.89.
3
13C NMR (75 MHz, CDCl
05.6 (d), 118.8 (d), 126.9 (d), 127.3 (d), 127.8 (d), 128.9 (s), 129.0
): d = 16.5 (q), 39.2 (t), 41.2 (d), 55.2 (q),
+
3
MS (EI): m/z (%) = 224 (M , 83), 165 (100).
1
HRMS (EI): m/z calcd for C H O P: 224.0813; found: 224.0820.
8
17
5
(d), 133.2 (s), 134.1 (s), 157.3 (s), 182.6 (s).
+
MS (EI): m/z (%) = 244 (M , 27), 171 (100).
3
-(6-Methoxynaphthalen-2-yl)-2-methylacrylic Acid Methyl
Ester (18)
HRMS (EI): m/z calcd for C15H O : 244.1099; found: 244.1096.
16 3
Wittig–Horner reagent 16 (380 mg, 1.70 mmol) was added at 0 °C
to a suspension of NaH (100 mg, 4.17 mmol) in DME (10 mL) with
the evolution of hydrogen gas. After stirring this mixture for 1 h at
Anal. Calcd for C H O : C, 73.8; H, 6.6. Found: C, 73.9; H, 6.8.
1
5
16
3
Synthesis 2005, No. 11, 1789–1796 © Thieme Stuttgart · New York

PAPER
-Methoxy-2-methyl-2,3-dihydro-1H-cyclopenta[a]naphtha-
Functionalized Molecular Motors
1795
1
7
H NMR (400 MHz, CDCl ): d = 0.25 (s, 6 H), 1.03 (s, 9 H), 1.37
3
len-1-one (21)
(d, J = 7.3 Hz, 3 H), 2.77–2.84 (m, 2 H), 3.46 (dd, J = 18.0, 8.1 Hz,
1 H), 7.24–7.27 (m, 2 H), 7.46 (d, J = 8.4 Hz, 1 H), 7.91 (d, J = 8.4
Hz, 1 H), 9.05 (d, J = 9.9 Hz, 1 H).
Acid 20 (0.771 g, 3.16 mmol) dissolved in CH Cl (50 mL) was
2
2
heated at reflux with SOCl (2.00 mL, 3.26 g, 27.4 mmol) and a cat-
2
alytic amount of DMF. After 1 h the reaction mixture was allowed
to cool to r.t. and all volatiles were removed under reduced pressure
giving a yellow oil. This oil was dissolved in toluene and cooled to
13
C NMR (100 MHz, CDCl ): d = –4.5 (q), 16.4 (q), 18.0 (s), 25.5
3
(
q), 34.8 (t), 42.1 (d), 115.5 (d), 124.02 (d), 124.05 (d), 124.7 (s),
1
25.2 (d), 129.8 (d), 134.0 (s), 134.2 (d), 153.7 (s), 154.2 (s), 209.5
0
°C whereupon AlCl (0.534 g, 4.00 mmol) was added in one por-
3
(
s).
tion. The greenish reaction mixture was stirred for 1 h at 0 °C after
which it was acidified with an aq soln of HCl (10%). Extraction
+
MS (EI): m/z (%) = 326 (M , 100).
with EtOAc (3 × 100 mL), drying of the organic layers (MgSO ),
4
HRMS (EI): m/z calcd for C H O Si: 326.1702, found: 326.1703.
2
0
26
2
and subsequent removal of the volatiles gave a brown oil. Purifica-
tion using column chromatography (SiO ; heptane–EtOAc, 8:1; R
2
f
7,7¢-Bis(tert-butyldimethylsilanyloxy)-2,2¢-dimethyl-2,3,2¢,3¢-
tetrahydro[1,1¢]bi[cyclopenta-[a]naphthalenylidene] (24)
Using similar reaction conditions as were used for the synthesis of
5, ketone 23 (0.619 g, 1.90 mmol) was refluxed in a mixture of the
0
.38) gave the desired ketone 21 as a colorless oil (0.650 g, 2.88
mmol, 91%).
1
H NMR (300 MHz, CDCl ): d = 1.37 (d, J = 7.3 Hz, 3 H), 2.76–
3
McMurry reagent prepared from TiCl (0.420 mL, 0.722 g, 3.82
2
.83 (m, 2 H), 3.45 (dd, J = 17.9, 8.1 Hz, 1 H), 3.93 (s, 3 H), 7.21
4
mmol) and Zn powder (0.497, 7.60 mmol) in THF (15 mL). After
standard workup, the crude product was purified by column chro-
matography and was obtained as a yellow oil (0.530 g, 0.855 mmol,
(
d, J = 2.9 Hz, 1 H), 7.32 (dd, J = 9.2, 2.9 Hz, 1 H), 7.47 (d, J = 8.4
Hz, 1 H), 7.95 (d, J = 8.4 Hz, 1 H), 9.06 (d, J = 9.2 Hz, 1 H).
1
3
C NMR (75 MHz, CDCl ): d = 16.5 (q), 35.1 (t), 42.3 (d), 55.1 (q),
3
9
0%), which solidified upon standing. The cis isomer was obtained
1
06.7 (d), 120.5 (d), 124.3 (d), 124.5 (s), 125.2 (d), 130.0 (s), 134.0
pure by recrystallization from EtOH as yellow needles. Unfortu-
nately, the trans isomer was not obtained in pure form; the data for
trans-24 were derived from a mixture of cis and trans.
(
s), 134.4 (d), 153.9 (s), 157.7 (s), 209.8 (s).
+
MS (EI): m/z (%) = 226 (M , 100), 211 (67).
HRMS (EI): m/z calcd for C H O : 226.0994, found: 226.0999.
1
5
14
2
cis-24
Mp 169.3–170.7 °C.
7
-Hydroxy-2-methyl-2,3-dihydrocyclopenta[a]naphthalen-1-
1
one (22)
H NMR (400 MHz, CDCl ): d = 0.04 (s, 6 H), 0.06 (s, 6 H), 0.90
3
To an ice-cooled suspension of AlCl (8.00 g, 60.0 mmol) in CH Cl
(s, 18 H), 1.21 (d, J = 6.6 Hz, 6 H), 2.63 (d, J = 14.4 Hz, 2 H), 3.50–
3
2
2
(
25 mL), Me N·HCl (2.87 g, 30 mmol) was added carefully. The
3.61 (m, 4 H), 6.00 (dd, J = 9.2, 2.6 Hz, 2 H), 6.48 (d, J = 9.2 Hz,
3
mixture was stirred at r.t. for 2 h, a brown solution was obtained. To
this solution was added 21 (0.800 g, 3.54 mmol) dissolved in a small
amount of CH Cl whereupon the reaction mixture turned dark
brown. The organic volatiles were removed and the reaction mix-
ture was stirred at 80 °C overnight. The dark brown reaction mix-
2 H), 7.01 (d, J = 2.6 Hz, 2 H), 7.42 (d, J = 8.1 Hz, 2 H), 7.55 (d,
J = 8.1 Hz, 2 H).
2
2
13
C NMR (100 MHz, CDCl ): d = –4.6 (q), –4.5 (q), 18.1 (s), 20.8
3
(
(
q), 25.7 (q), 40.5 (t), 42.2 (d), 115.1 (d), 120.3 (d), 123.7 (d), 125.7
s), 127.2 (d), 128.0 (d), 133.6 (s), 136.8 (s), 140.0 (s), 142.0 (s),
ture was poured carefully into H O (200 mL) followed by
2
1
51.9 (s).
acidification with an aq soln of HCl (10%; 100 mL), and extraction
with CH Cl (3 × 100 mL). The combined organic layers were dried
2
2
trans-24
(
Na SO ) and evaporated under reduced pressure giving a brown
1
2
4
H NMR (400 MHz, CDCl ): d = 0.28 (s, 6 H), 0.29 (s, 6 H), 1.05
3
solid, which was purified by column chromatography (SiO , hep-
2
(
(
s, 18 H), 1.28 (d, J = 6.6 Hz, 6 H), 2.30 (d, J = 14.7 Hz, 2 H), 2.92
dd, J = 14.7, 5.5 Hz, 2 H), 3.00–3.07 (m, 2 H), 7.13 (dd, J = 9.2,
tane–EtOAc, 4:1, R 0.39) giving a white solid (0.581 g, 2.74 mmol,
f
7
7%).
2
.6 Hz, 2 H), 7.26 (d, J = 2.6 Hz, 2 H), 7.33 (d, J = 8.1 Hz, 2 H),
Mp 150.9–153.7 °C.
7.60 (d, J = 8.1 Hz, 2 H), 8.12 (d, J = 9.2 Hz, 2 H).
1
13
H NMR (400 MHz, CDCl ): d = 1.32 (d, J = 7.3 Hz, 3 H), 2.72–
C NMR (100 MHz, CDCl ): d = –4.2 (q), 18.3 (s), 19.4 (q), 25.8
3
3
2
7
9
.78 (m, 2 H), 3.40 (dd, J = 17.5, 7.5 Hz, 1 H), 5.21 (s, 1 H), 7.19–
.24 (m, 2 H), 7.41 (d, J = 8.4 Hz, 1 H), 7.85 (d, J = 8.4 Hz, 1 H),
.02 (d, J = 8.8 Hz, 1 H).
(q), 41.1 (t), 43.0 (d), 115.3 (d), 121.1 (d), 124.4 (d), 126.1 (s), 126.5
(d), 128.2 (d), 134.2 (s), 138.6 (s), 139.6 (s), 141.5 (s), 152.5 (s).
+
MS (EI): m/z (%) = 620 (M , 100).
1
3
C NMR (100 MHz, CDCl ): d = 16.7 (q), 35.2 (t), 42.5 (d), 110.4
3
HRMS (EI): m/z calcd for C H O Si : 620.3506; found: 620.3525.
4
0
52
2
2
(
d), 120.2 (d), 124.5 (s), 124.6 (d), 125.8 (d), 130.2 (s), 134.3 (s),
1
34.5 (d), 154.2 (s), 154.5 (s), 210.7 (s).
2
,2¢-Dimethyl-2,3,2¢,3¢-tetrahydro[1,1¢]bi[cyclopenta[a]naph-
+
MS (EI): m/z (%) = 212 (M , 100), 197 (87).
thalenylidene]-7,7¢-diol (25)
To a solution of cis-24 (110 mg, 177 mmol) dissolved in THF (10
mL) was added TBAF (excess). The color of the reaction mixture
turned rapidly from slightly green to orange. After stirring for 10
HRMS (EI): m/z calcd for C H O : 212.0837; found: 212.0852.
1
4
12
2
7
-(tert-Butyldimethylsilanyloxy)-2-methyl-2,3-dihydrocyclo-
min, the reaction mixture was poured into a sat. soln of NH Cl (50
4
penta[a]naphthalen-1-one (23)
A mixture of the phenol 22 (0.530 g, 2.50 mmol), TBDMSiCl
mL) and acidified to pH 2 with an aq soln of HCl (30%). The reac-
tion mixture was extracted with Et O (2 × 50 mL) and then washed
2
(
0.768 g, 5.00 mmol) and DMAP (0.610 g, 5.00 mmol) was stirred
with brine (2 × 50 mL). After drying (Na SO ) and evaporation, a
2
4
overnight in CH Cl (50 mL). The mixture was then washed with
2
2
yellow oil was obtained which was purified by flash column chro-
HCl (1 N; 2 × 100 mL) and brine (100 mL), dried (Na SO ) and then
2
4
matography (SiO , heptane–EtOAc, 1:1; R 0.8) and the product
2
f
all volatiles were removed under reduced pressure. The crude prod-
was finally obtained as a white solid (65.9 mg, 168 mmol, 95%).
This solid, however, was not very stable, since it rapidly colored
green after 30 min and went black overnight. The reaction has also
been performed with a mixture of cis-24 and trans-24 giving a sim-
ilar yield.
uct was purified by column chromatography (SiO ; heptane–
2
EtOAc; R 0.5) and was obtained as slightly yellow solid (0.64 g,
f
1
.96 mmol, 79%).
Mp 103.5–105.5 °C.
Synthesis 2005, No. 11, 1789–1796 © Thieme Stuttgart · New York

1
796
M. K. J. ter Wiel, B. L. Feringa
PAPER
(4) Jiménez, M. C.; Dietrich-Buchecker, C.; Sauvage, J.-P.
cis-25
Mp >250 °C.
Angew. Chem. Int. Ed. 2000, 39, 3284.
(5) Badjic, J. D.; Balzani, V.; Credi, A.; Silvi, S.; Stoddart, J. F.
Science 2004, 303, 1845.
1
H NMR (300 MHz, CDCl ): d = 1.20 (d, J = 6.6 Hz, 6 H), 2.64 (d,
3
J = 14.3 Hz, 2 H), 3.46–3.61 (m, 4 H), 4.76 (s, 2 H), 6.04 (dd, J =
(
(
(
6) Muraoka, T.; Kinbara, K.; Kobayashi, Y.; Aida, T. J. Am.
9
.2, 2.6 Hz, 2 H), 6.52 (d, J = 9.2 Hz, 2 H), 7.00 (d, J = 2.6 Hz, 2
Chem. Soc. 2003, 125, 5612.
7) Thordarson, P.; Bijsterveld, E. J. A.; Rowan, A. E.; Nolte, R.
J. M. Nature (London, UK) 2003, 424, 915.
H), 7.43 (d, J = 8.1 Hz, 2 H), 7.54 (d, J = 8.1 Hz, 2 H).
trans-25
8) Koumura, N.; Zijlstra, R. W. J.; van Delden, R. A.; Feringa,
Spectral data obtained from a mixture containing cis-25.
B. L. Nature (London, UK) 1999, 401, 152.
1
H NMR (300 MHz, CDCl ): d = 1.27 (d, J = 6.6 Hz, 6 H), 2.30 (d,
3
(9) (a) Koumura, N.; Geertsema, E. M.; Meetsma, A.; Feringa,
B. L. J. Am. Chem. Soc. 2000, 122, 12005. (b) Koumura,
N.; Geertsema, E. M.; van Gelder, M. B.; Meetsma, A.;
Feringa, B. L. J. Am. Chem. Soc. 2002, 124, 5037.
J = 14.3 Hz, 2 H), 2.92 (dd, J = 14.3, 5.5 Hz, 2 H), 3.00–3.05 (m, 2
H), 5.20 (s, 2 H), 7.16 (dd, J = 9.2, 2.6 Hz, 2 H), 7.23 (d, J = 2.6 Hz,
2
H), 7.34 (d, J = 8.1 Hz, 2 H), 7.59 (d, J = 8.1 Hz, 2 H), 8.15 (d,
J = 9.2 Hz, 2 H).
Due to the instability and low solubility of the compound, no 13C
NMR spectrum could be obtained.
(
(
(
(
10) ter Wiel, M. K. J.; Delden, R. A.; van Meetsma, A.; Feringa,
B. L. J. Am. Chem. Soc. 2003, 125, 15076.
11) Flood, A. H.; Ramirez, R. J. A.; Deng, W. Q.; Muller, R. P.;
Goddard, W. A.; Stoddart, J. F. Aust. J. Chem. 2004, 57, 301.
12) ter Wiel, M. K. J.; van Delden, R. A.; Meetsma, A.; Feringa,
B. L. J. Am. Chem. Soc., submitted.
+
MS (EI): m/z (%) = 392 (M , 100).
HRMS (EI): m/z calcd for C H O : 392.1776; found: 392.1797.
2
8
24
2
13) (a) Short, W. F.; Stromberg, H.; Wiles, A. E. J. Chem. Soc.
1
936, 319. (b) Bachmann, W. E.; Horton, W. J. J. Am.
Acknowledgment
Chem. Soc. 1947, 69, 58.
(
(
(
14) Ghosal, M. J. Org. Chem. 1960, 25, 1856.
15) This work is in progress.
16) (a) Gerlach, H.; Wetter, H. Helv. Chim. Acta 1974, 57,
Financial support from the Netherlands Organization for Scientific
Research (NWO-CW) is gratefully acknowledged.
2306. (b) Hoover, H. W. Jr.; McCall, M. A.; Dickey, J. B. J.
Am. Chem. Soc. 1957, 79, 1963.
17) Harvey, R. G.; Cortez, C.; Sawyer, T. W.; DiGiovanni, J. J.
Med. Chem. 1988, 31, 1308.
18) Kemperman, G. J.; Roeters, T. A.; Wilberink, P. W. Eur. J.
Org. Chem. 2003, 1681.
19) Wrobel, J.; Dietrich, A.; Gorham, B. J.; Sestanj, K. J. Org.
Chem. 1990, 55, 2694.
20) Koelsch, C. F. Org. Synth. 1940, 20, 18.
References
(
(
(
(
(
1) Peercy, P. S. Nature (London, UK) 2000, 406, 1023.
2) (a) Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart, J. F.
Angew. Chem. Int. Ed. 2000, 39, 3348. (b) Feringa, B. L.;
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Synthesis 2005, No. 11, 1789–1796 © Thieme Stuttgart · New York