Tuning of the electronic properties of a cyclopentadienylruthenium catalyst to match racemization of electron-rich and electron-deficient alcohols

Article abstract of DOI:10.1002/chem.201100827

The synthesis of a new series of cyclopentadienylruthenium catalysts with varying electronic properties and their application in racemization of secondary alcohols are described. These racemizations involve two key steps: 1) β-hydride elimination (dehydrogenation) and 2) re-addition of the hydride to the intermediate ketone. The results obtained confirm our previous theory that the electronic properties of the substrate determine which of these two steps is rate determining. For an electron-deficient alcohol the rate-determining step is the β-hydride elimination (dehydrogenation), whereas for an electron-rich alcohol the re-addition of the hydride becomes the rate-determining step. By matching the electronic properties of the catalyst with the electronic properties of the alcohol, we have now shown that a dramatic increase in racemization rate can be obtained. For example, electron-deficient alcohol 15 racemized 30 times faster with electron-deficient catalyst 6 than with the unmodified standard catalyst 4. The application of these protocols will extend the scope of cyclopentadienylruthenium catalysts in racemization and dynamic kinetic resolution. Copyright

Full text of DOI:10.1002/chem.201100827

DOI: 10.1002/chem.201100827
Tuning of the Electronic Properties of a Cyclopentadienylruthenium Catalyst
to Match Racemization of Electron-Rich and Electron-Deficient Alcohols
Oscar Verho, Eric V. Johnston, Erik Karlsson, and Jan-E. Bꢀckvall*[a]
Abstract: The synthesis of a new series
of cyclopentadienylruthenium catalysts
with varying electronic properties and
their application in racemization of sec-
ondary alcohols are described. These
racemizations involve two key steps:
1) b-hydride elimination (dehydrogena-
tion) and 2) re-addition of the hydride
to the intermediate ketone. The results
obtained confirm our previous theory
that the electronic properties of the
substrate determine which of these two
steps is rate determining. For an elec-
tron-deficient alcohol the rate-deter-
mining step is the b-hydride elimina-
tion (dehydrogenation), whereas for an
electron-rich alcohol the re-addition of
the hydride becomes the rate-deter-
mining step. By matching the electronic
properties of the catalyst with the elec-
tronic properties of the alcohol, we
have now shown that a dramatic in-
crease in racemization rate can be ob-
tained. For example, electron-deficient
alcohol 15 racemized 30 times faster
with electron-deficient catalyst 6 than
with the unmodified standard catalyst
4. The application of these protocols
will extend the scope of cyclopentadie-
nylruthenium catalysts in racemization
and dynamic kinetic resolution.
Keywords: alcohols
· cyclopenta-
dienyl ligands · dynamic kinetic res-
olution · racemization · ruthenium
Introduction
of Shvoꢀs ruthenium catalyst 1[4] in combination with an im-
mobilized lipase.
The demand for methods to produce chiral compounds as
single enantiomers has increased dramatically in recent
years. This is mainly driven by the pharmaceutical industry
and suppliers of agrochemicals, flavors, fragrances, and ma-
terials, resulting in extensive re-
This protocol was later extended to functionalized secon-
dary alcohols such as hydroxyacid derivatives,[5,6] various b-
substituted alcohols,[2a] and diols.[7] Shvoꢀs catalyst has also
been applied to DKR of primary amines,[8] in which the cat-
search in the field of asymmet-
ric synthesis.[1] Dynamic kinetic
resolution (DKR) has proven
to be a powerful and efficient
tool for the preparation of
enantiomerically pure alco-
hols.[2] In these reactions, race-
mization of the alcohol occurs
in situ by, for example, a transi-
tion-metal complex, in parallel
with an enzymatic resolution,
resulting in a DKR with a max-
imum theoretical yield of 100%
of the enantiopure compound.
In 1997, our group reported[3]
an efficient DKR method for
the synthesis of enantiopure
secondary alcohols by the use
alyst was also subject for electronic modifications, showing
that electron-rich substituents on the catalyst lead to more
efficient racemization. However, catalyst 1 has two major
drawbacks; it requires heat activation and when the re-addi-
tion of hydride to the carbonyl is too slow due to steric or
electronic factors it is prone to evolve hydrogen gas, which
results in the formation of ketone. These limitations were
later overcome by the use of catalysts 2,[9] 4,[10] and 7,[11]
[a] O. Verho, E. V. Johnston, E. Karlsson, J.-E. Bꢁckvall
Department of Organic Chemistry
Arrhenius Laboratory, Stockholm University
10691 Stockholm (Sweden)
E-mail: jeb@organ.su.se
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100827.
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FULL PAPER
which allow for a highly efficient DKR of alcohols at room
temperature. In particular catalysts 4 and 7 give fast racemi-
zation reactions at room temperature and these systems
have been applied to DKR reactions of various secondary
alcohols[12,13] and they allow for scale-up to 100 g–1 kg
scales.[14] Recently, Kim and Park reported on substituent ef-
fects on the catalytic activity of [{h5-Ar4C4COC(=O)Ar}Ru-
(CO)2Cl] in racemization of secondary alcohols.[15]
Dyker and coworkers,[16] it was possible to obtain 12d. Al-
though the yield of the reaction is low, it has the advantage
of providing the target ligand in one step from simple start-
ing materials. The low yield was due to significant formation
of tri- and tetra-arylated byproducts resulting in a compli-
cated purification procedure. Ligand 12d was then allowed
to react with triruthenium dodecacarbonyl affording the de-
sired analogue 6.
The analogues 3–6 were tested in racemization of secon-
dary alcohols 14–17 with different electronic properties, to
investigate how the rate of racemization depends on the
nature of the substrates for the different catalysts 3–6.
Results and Discussion
Herein, we report on the synthesis and applications of a
new series of electron-deficient and electron-rich analogues
of catalyst 4. The analogues 3, 5, and 6 were synthesized by
two different routes presented in Scheme 1. Route A, previ-
ously developed by our group for the synthesis of catalyst 4,
was applied to the synthesis of analogues 3 and 5.[10] For the
synthesis of the highly electron-deficient analogue 6, this
route proved to be unsuccessful, due to an inefficient con-
densation between the corresponding ketone 9 and diketone
10. However, by changing to route B, a Pd-catalyzed aryla-
tion reaction of cyclopentadiene previously reported by
It is known that racemization occurs by an inner-sphere
redox-mechanism (Scheme 2), in which the catalytically
active tBuO-species, generated from 4 and tBuOK, first un-
dergoes an alcohol–alkoxide exchange with the substrate al-
Scheme 1. i) EDC·HCl, DMAP, CH2Cl2, RT. ii) 10, NaOH (aq), EtOH, 508C. iii) 1) Ar-MgBr (R=Ph, p-F-Ph, p-MeO-Ph), THF, RT; 2) LiAlH4, THF,
RT. iv) 1) Ru3(CO)12, decane, toluene, 1608C; 2) CHCl3, decane, toluene, 1608C. v) 4-Bromobenzotrifluoride, Pd
1408C. vi) 1) Ru3(CO)12, decane, toluene, 1608C; 2) CHCl3, decane, toluene, 1608C.
ACHTNUGTRNEUN(GN OAc)2, tBuPHBH4, Cs2CO3, DMF,
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J.-E. Bꢁckvall et al.
Figure 1. Racemization of 14: [(h5-C5Ar5)RuCl(CO)2] (4.69 mmol) and
Na2CO3 (0.19 mmol) were mixed in toluene (1.5 mL) and the mixture
was heated to 808C. tBuOK (14.1 mmol dissolved in 40 mL of dry THF)
was then added. After 10 min, enantiopure alcohol 14 (0.19 mmol) was
added (t=0) and the mixture was kept at 808C. The ee value of the alco-
hol was determined for periodic aliquots by chiral GC.
Scheme 2. Proposed mechanism for the racemization of secondary alco-
hols with catalyst 4.
cohol, to form 4a.[10,17] Subsequent b-hydride elimination
produces the ketone–hydride complex 4b, in which the
ketone remains coordinated until it is reduced by the hy-
dride from either face to give the racemic alkoxide complex
4c. The racemic alkoxide is then released by another alco-
hol–alkoxide exchange and the catalytic cycle is repeated.
The exact nature of the ketone–hydride complex had been
difficult to establish in earlier studies,[17] but recent results
indicate that the empty coordination site necessary for the
b-hydride elimination is generated by CO dissociation.[18]
The rate-determining step for the racemization of elec-
tron-deficient alcohols by 4 is thought to be the b-hydride
elimination (dehydrogenation) step, since these substrates
are less prone to undergo oxidation to the corresponding
ketone. The theory of a rate-determining b-hydride elimina-
tion for electron-deficient alcohols is supported by previous
results from our group,[19] in which elevated temperatures
and extended reaction times were required for the racemiza-
tion of these substrates, when employing catalyst 4. An elec-
tron-deficient catalyst would speed up the rate of the b-hy-
dride elimination from the alkoxide intermediate of these
electron-deficient alcohols, and result in a more efficient
overall racemization.
To elucidate the electronic effects of the racemization cat-
alysts, racemization of electron-deficient substrates 14 and
15 with the four cyclopentadienyl ruthenium catalysts 3–6
were studied. Substrates 14 and 15 were previously shown to
racemize at a low rate with catalyst 4. However, with more
electron-deficient catalysts a faster racemization is expected.
Indeed, as shown in Figures 1 and 2 a fast racemization was
obtained with the most electron-deficient catalyst 6, which
was found to be >10 times faster than the unmodified cata-
lyst 4 for substrate 14 and 30 times faster than the unmodi-
fied catalyst 4 for substrate 15. Catalyst 5, also showed im-
proved efficiency compared with catalyst 4, and gave almost
complete racemization within 10 min. On the other hand,
electron-rich catalyst 3 exhibited moderate to poor perfor-
mance in both studies with only partial racemization after
30 min (26% enantiomeric excess (ee) for 14 and 42% ee
Figure 2. Racemization of 15: [(h5-C5Ar5)RuCl(CO)2] (4.69 mmol) and
Na2CO3 (0.19 mmol) were mixed in toluene (1.5 mL), and the mixture
was heated to 608C. tBuOK (14.1 mmol dissolved in 40 mL of dry THF)
was then added. After 10 min, enantiopure alcohol 15 (0.19 mmol) was
added (t=0) and the mixture was kept at 608C. The ee value of the alco-
hol was determined for periodic aliquots by chiral GC.
for 15). In a recent publication Kim and Park[15] studied the
electronic effects for a related cyclopentadienylruthenium
catalyst. From their results the authors concluded that an
electron-rich catalyst was “the most efficient and practical
racemization catalyst for the DKR of secondary alco-
hols”.[15] Our results show that this no longer applies for the
racemization of highly electron-deficient alcohols, such as 14
and 15, and that in these cases an electron-deficient catalyst
is required for an efficient racemization.
In the racemization of electron-rich substrates the ratio of
the relative rates of hydride abstraction (b-elimination) and
re-addition of hydride (insertion) will be larger than for
electron-deficient alcohols. For electron-rich substrates the
hydride re-addition is the rate-determining step for catalyst
4. For an electron-rich substrate, an electron-rich catalyst
would give a faster re-addition of the hydride to the coordi-
nated electron-rich ketone than an electron-deficient cata-
lyst and thus give the most efficient overall racemization. As
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Tuning of the Electronic Properties of a Cyclopentadienylruthenium Catalyst
FULL PAPER
predicted, the relative rates of catalysts 3–6 in the racemiza-
tion of (S)-1-phenylethanol (16) and (S)-1-(4-methoxyphe-
nyl)ethanol (17) (Figures 3 and 4) at room temperature,
showed the opposite trend to that of alcohols 14 and 15.
the activation times[20] of catalysts 3–6 at room temperature,
and we observed a trend in the activation rate. Catalysts 3
and 4 were fully activated within 10 min, whereas catalyst 5
required a slightly longer activation time (ꢀ30 min). The
most electron-deficient catalyst 6 was not fully activated
even after 90 min, which was reflected by the irregular
shape of its racemization curve in Figure 3.
In the racemization of (S)-1-(4-methoxy)phenylethanol
(17) minor ketone formation could be observed for all cata-
lysts, which supports the theory of the hydride re-addition
being the rate-limiting step. As expected, the amount of
ketone produced for catalysts 3–6 was lowest for catalyst 3
(5%). For catalysts 4, 5, and 6 ketone formation from sub-
strate 17 was 6, 8, and 7%, respectively. Interestingly,
ketone formation did not seem to lead to catalyst deactiva-
tion. Ketone formation was not observed for any of the
other substrates (14, 15, or 16).
The relative rate of carbon monoxide exchange from cata-
lysts 3–6 is thought to have a minor or negligible effect on
the rate of racemization. We have recently studied the rate
of CO exchange for both the chloride precursor (h5-
C5Ar5)RuCl(CO)2 (4) and the active tert-butoxide derivative
Figure 3. Racemization of 16: [(h5-C5Ar5)RuCl(CO)2] (3.80 mmol) and
Na2CO3 (0.38 mmol) were mixed in toluene (1.5 mL) and tBuOK
(11.4 mmol, dissolved in 40 mL of dry THF) was added. Activation time:
catalysts 3 and 4: 10 min, catalyst 5: 30 min, catalyst 6: 60 min. After
completed activation enantiopure alcohol 16 (0.38 mmol) was added (t=
0). The reaction was carried out at room temperature. The ee value of
the alcohol was determined for periodic aliquots by chiral GC.
ACTHNUTRGNEUNG
(h5-C5Ar5)Ru(OtBu)(CO)2.[18] CO-exchange in the tert-but-
oxide derivative is about one order of magnitude faster than
that of the chloride precursor, which is explained by a more
efficient back donation of electrons by the alkoxy-group,
and this lowers the energy of the transition state.[18] We be-
lieve that the difference between an alkoxide and a chloride
is much larger than that between the alkoxides of the differ-
ent alcohol used.
Furthermore, an electron-rich cyclopentadienyl ligand
should favor CO dissociation and formation of the 16-elec-
tron complex 4b in Scheme 2 through p back-donation
much better than an electron-deficient cyclopentadienyl.
This could potentially have a beneficial effect on the racemi-
zation rate. However, we have shown that in the racemiza-
tion of electron-deficient alcohols (Figures 1 and 2), the
most efficient racemization is obtained with an electron-de-
ficient catalyst. If it were determined mainly by the CO dis-
sociation it would have been the opposite (i.e., an electron-
rich catalyst would have been the best). This shows that the
impact of the relative rate of carbon monoxide exchange be-
tween catalysts 3–6 has a minor effect on the rate of racemi-
zation at least for electron-deficient alcohols. For electron-
rich alcohols/ketones we cannot rule out that there is an
effect also from the rate of dissociation of the CO in the dif-
ferent catalysts. However, we believe that the major contri-
bution comes from the faster re-addition of the hydride for
the electron-rich catalysts.
Figure 4. Racemization of 17: [(h5-C5Ar5)RuCl(CO)2] (3.80 mmol) and
Na2CO3 (0.38 mmol) were mixed in toluene (1.5 mL) and tBuOK
(11.4 mmol dissolved in 40 mL of dry THF) was added. Activation time:
catalysts 3 and 4: 10 min, catalyst 5: 30 min, catalyst 6: 60 min. After
completed activation enantiopure alcohol 17 (0.38 mmol) was added (t=
0). The reaction was carried out at room temperature. The ee value of
the alcohol was determined by periodic aliquots for chiral GC.
Catalyst 3 now gave the fastest racemization, supporting the
theory of a shift of the rate-determining step from the b-hy-
dride elimination to the hydride re-addition step. The elec-
tron-deficient catalysts 5 and 6 showed significantly lower
efficiency than the unmodified catalyst 4, which is due to
the electron-deficient catalysts being very slow in the re-ad-
dition of the hydride to the electron-rich ketone. The poor
performance of catalyst 6, particularly in the racemization
of 17 (Figure 4), is not entirely based on a substrate mis-
match but also due to an insufficient activation of the cata-
lyst at room temperature. These results led us to investigate
Conclusion
We have reported the synthesis of electronically modified
(pentaarylcyclopentadienyl)ruthenium complexes 3, 5, and 6
and studied the racemization of electron-deficient (14 and
15) and electron-rich (16 and 17) secondary alcohols with
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J.-E. Bꢁckvall et al.
layer was separated and washed with dilute aqueous HCl (3ꢃ50 mL) and
saturated aqueous NaHCO3 (3ꢃ50 mL). After treatment with anhydrous
MgSO4, the solvent was evaporated to give a yellow solid (1.38 g, 48%).
1H NMR (400 MHz, CDCl3); spectral data were in accordance with those
previously reported in the literature.[23]
catalysts 3–6. It was found that a faster racemization rate
was achieved by matching the electronic properties of the
substrate and the catalyst. Thus, electron-deficient alcohols
14 and 15 gave the fastest racemization with electron-defi-
cient catalysts 5 and 6, whereas electron-rich systems 16 and
17 afforded the fastest racemization with electron-rich cata-
lysts 3 and 4. The results demonstrate how the relative rates
of abstraction and re-addition of hydride change with the
electronic properties of the substrate and catalyst in the
ruthenium-catalyzed racemization. Furthermore, it was
shown that the efficiency of the racemization can be opti-
mized by adjusting the electronic properties of the catalyst
to the electronic properties of the substrate. This will extend
the scope of the use of cyclopentadienylruthenium catalysts
in racemization and dynamic kinetic resolution.
Synthesis of 2,3,4,5-tetrakis(4-methoxyphenyl)cyclopentadienone (11a):
Aqueous NaOH (2.0m, 43 mL, 85.44 mmol) was slowly added to a stirred
solution of 1,3-bis(4-methoxyphenyl)-2-propanone (9a) (4.35 g,
16.1 mmol) and 1,2-di(4-methoxyphenyl)benzil (10a) (4.35 g, 16.1 mmol)
in EtOH (60 mL). The resulting solution was stirred at 508C for 2 h. The
reaction was then cooled on an ice bath for 30 min. The precipitate
formed was collected by filtration and washed with EtOH (3ꢃ25 mL)
and pentane (3ꢃ25 mL), to give the desired product as a dark purple
solid (6.77 g, 83%). No further purification was needed. Spectral data
were in accordance with those previously reported in the literature.[23]
Experimental Section
All reagents obtained from commercial suppliers were of analytical
grade and were used without further purification. Anhydrous solvents
were purchased from Sigma and reagents were purchased from Sigma
and Apollo (fluorinated compounds).
Diethyl ether, THF, and toluene were column dried directly before use
from VAC:SOLVENT PURIFIER.
Substrates 14, 15, and 17 were prepared from commercially available
starting materials according to literature procedures given below. The
corresponding chloromethyl aryl ketone of substrate 14 was obtained
from the chlorination reaction of the methyl aryl ketone (Sigma) with N-
chlorosuccinimide (NCS).[21] Subsequent reduction by NaBH4 and kinetic
resolution employing PS-C lipase (Amano),[19] afforded the substrate 14
in excellent ee. Substrate 15 was prepared from (S)-oxiranylanisole
(Sigma), in a nucleophilic epoxide-opening reaction, using Li2CuCl4.[22]
Substrate 17 was prepared from the corresponding ketone, by reduction
with NaBH4 and kinetic resolution employing CAL-B lipase (Amano).
Substrate 16 was purchased from Sigma.
Synthesis of 1,2,3,4,5-penta(4-methoxyphenyl)-1,3-cyclopentadiene (12a):
A solution of 1-bromoanisole 2.56 g, 13.6 mmol) in THF (20 mL) was
added dropwise to a suspension of Mg turnings (0.33 g, 13.6 mmol) in
THF (10 mL) under an inert atmosphere. The resulting mixture was
stirred at RT for 2 h, followed by addition of 2,3,4,5-tetrakis(4-methoxy-
phenyl)cyclopentadienone (11a) (4.00 g, 9.08 mmol) in one portion. The
reaction mixture was allowed to stir for an additional 5 h, before LiAlH4
(0.70 g, 18.15 mmol) was added and the reaction was stirred overnight
(16 h). The reaction was quenched with EtOAc (10 mL) and then diluted
with H2O (5 mL). The diluted mixture was extracted with CH2Cl2 (3ꢃ
50 mL), and the combined organic
phases were dried over anhydrous
MgSO4 and concentrated under re-
duced pressure to give a black solid.
Purification of the black solid by
column chromatography (pentane/
EtOAc 80:20) gave the desired prod-
uct as a pale green solid (2.01 g, 37%).
All reactions were monitored by thin layer chromatography (TLC) using
silica gel-coated plates with indicator (Merck, Silica gel 60). Column
chromatography was performed on silica gel (Grace Division, Davsil,
0.035–0.070 mm) unless otherwise mentioned. After chromatography the
fractions were pooled, evaporated to dryness and dried in vacuo.
1H NMR, 13C NMR, and 19F NMR spectroscopy were recorded on
Bruker Avance 400 MHz instrument. Chemical shifts are reported in
ppm, relative to TMS (1H; internal standard, dH =0.00 ppm) or solvent
peaks (1H: CDCl3 dH =7.26 ppm and [D6]DMSO dH =2.50 ppm; 13C:
CDCl3 dC =77.0 ppm and [D6]DMSO dC =39.5 ppm). High resolution
mass spectra (HRMS) were recorded on a Bruker MicroTOF ESI-TOF
mass spectrometer. IR spectra were recorded on a Perkin–Elmer spec-
trum 1 spectrophotometer. GC analysis was done on a Varian 3800 gas
chromatograph with a CP-Chirasil-Dex CB column (25 mꢃ0.32 mmꢃ
0.25 mm).
Spectral data were in accordance with
those previously reported in the litera-
ture.[16]
Synthesis of pentaACHTNUTRGNENG(U p-OMe-Ph)CpRu(CO)2Cl (3): 1,2,3,4,5-Penta(4-me-
thoxyphenyl)-1,3-cyclopentadiene (12a) (1.35 g, 2.26 mmol) and
[Ru3(CO)12] (0.58 mg, 0.90 mmol) were dissolved in a 2:1 mixture of
decane/toluene (12 mL) in a dry screw-cap tube, under an inert atmos-
phere. The resulting mixture was stirred at 1608C for 2.5 days, followed
by addition of CHCl3 (1.5 mL, 18.6 mmol), and it was allowed to stir at
1608C for an additional 1.5 h. Pentane (3 mL) was then added and the
mixture was filtered off to give a yellow solid. Further purification by
column chromatography (CH2Cl2) gave the product as a yellow solid
Synthesis of 1,3-bis(4-methoxyphenyl)-2-propanone (9a): 1-Ethyl-3-(3-
dimethyl
aminopropyl)carbodiimide (EDC)
hydrochloride
(4.04 g,
21.1 mmol) was added to a solution of 4-methoxyphenyl acetic acid (8a)
(3.00 g, 21.1 mmol) and 4-(dimethylamino)pyridine (DMAP) (2.83 g,
23.2 mmol) in CH2Cl2 (60 mL), and was allowed to stir at RT for 24 h.
The reaction mixture was then diluted with water (50 mL). The organic
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Tuning of the Electronic Properties of a Cyclopentadienylruthenium Catalyst
FULL PAPER
(1.20 g, 67%). 1H NMR (400 MHz,
CDCl3): d=6.95 (m, 10H; AA’ of
AA’BB’), 6.64 (m, 10H; BB’ of
AA’BB’), 3.75 ppm (s, 15H); 13C NMR
(100 MHz, CDCl3): d=197.4, 159.3,
133.5, 121.9, 113.2, 105.6, 55.1 ppm; IR
give a yellow solid. Further purification by column chromatography (pen-
tane/CH2Cl2 60:40) gave
yellow solid (203 mg, 30%). 1H NMR
a
(400 MHz, CDCl3): d=6.99 (m, 10H), 6.85 ppm (m, 10H); 13C NMR
(100 MHz, CDCl3): d=196.2, 162.6 (d, J=251 Hz), 133.9 (d, J=8.1 Hz),
124.9 (d, J=3.7 Hz), 115.4 (d, J=21 Hz), 105.3 ppm; 19F NMR
(400 MHz, CDCl3): d=À111.2 ppm; IR (KBr): n˜ =2050, 2006, 1607,
(KBr): n˜ =2038, 1986, 1609, 1518 cmÀ1
C42H35ClNaO7Ru+: 811.1007; found: 811.0974.
; MS (ESI-TOF): calcd for
1517 cmÀ1 MS (ESI-TOF): calcd for C37H20ClF5NaO2Ru+: 751.0008;
;
found: 750.9975; elemental analysis: calcd (%) for CxHxO2ClRu, C 61.04,
H 2.77; found: C 60.86, H 2.69.
Synthesis of 1,3-bis(4-fluorophenyl)-2-propanone (9c): 1-(3-Dimethylami-
nopropyl)-3-ethylcarbodiimide hydrochloride (10.0 g, 52.0 mmol) was
added to a solution of 4-fluorophenyl acetic acid (8c, 8.27 g, 53.6 mmol)
and 4-(dimethylamino)pyridine (7.06 g, 57.6 mmol) in CH2Cl2 (160 mL),
and was allowed to stir at RT for 24 h.
The reaction mixture was then diluted
with water (50 mL). The organic layer
was separated and washed with dilute
aqueous HCl (3ꢃ50 mL) and saturat-
ed aqueous NaHCO3 (3ꢃ50 mL).
After treatment with anhydrous
MgSO4, the solvent was evaporated to
give
a yellow solid (4.30 g, 68%).
Spectral data were in accordance with
those previously reported in the litera-
ture.[24]
Synthesis of 1,2,3,4,5-penta(4-trifluoromethylphenyl)-1,3-cyclopentadiene
(12d): Tri-tert-butylphosphonium tetrafluoroborate (0.36 g, 1.20 mmol),
palladium acetate (0.11 g, 0.50 mmol) and cesium carbonate (19.9 g,
61.2 mmol) were placed in a sealed tube under an inert atmosphere. To
this, distilled cyclopentadiene (13, 0.66 g, 10.0 mmol) and 4-bromobenzo-
trifluoride (13.5 g, 60.0 mmol), dissolved in dry DMF (20 mL) were
added. The resulting mixture was heated at 1408C for 16 h. The reaction
mixture was then transferred to a beaker and CH2Cl2 (250 mL) was
added, followed by addition of p-toluenesulfonic acid monohydrate
(1.90 g, 10.0 mmol). Filtration through a pad of SiO2 followed by concen-
tration under reduced pressure afforded a brown oil. Further purification
by column chromatography (solvent gradient: 1) pentane/CH2Cl2 98:2,
2) pentane/CH2Cl2 95:5 3) pentane/CH2Cl2 90:10) gave the desired prod-
Synthesis of 2,3,4,5-tetrakis(4-fluorophenyl)cyclopentadienone (11c):
Aqueous NaOH (2.0m, 43 mL, 85.44 mmol) was added, over 15 min, to a
stirred solution of 1,3-bis(4-fluorophenyl)-2-propanone (9c, 3.20 g,
13.0 mmol) and 1,2-di(4-fluorophenyl)-
benzil (10c, 3.20 g, 13.0 mmol) in
EtOH (250 mL). The resulting solu-
tion was stirred at 508C for 2 h. The
reaction was then cooled in an ice
bath for 30 min. The precipitate
formed was collected by filtration and
washed with EtOH (3ꢃ25 mL) and
pentane (3ꢃ25 mL), to give the de-
sired product as a dark purple solid
(3.81 g, 64%). No further purification
1
uct as a yellow solid (1.46 g, 19%). H NMR (400 MHz, CDCl3): d=7.48
(m, 6H), 7.35 (m, 4H), 7.28 (m, 2H), 7.11 (m, 4H), 7.00 (m, 4H),
5.20 ppm (s, 1H); 13C NMR (100 MHz, CDCl3): d=147.1, 144.2, 140.4 (t,
J=1.3 Hz), 138.2 (t, J=1.3 Hz), 137.9
was needed. Spectral data were in ac-
cordance with those previously report-
ed in the literature.[24]
(t, J=1.3 Hz), 130.3, 130.1 (q, J=
32.6 Hz), 130.0 (q, J=32.6 Hz), 129.5
(q, J=32.6 Hz), 129.2, 128.7, 126.3 (q,
J=3.8 Hz), 125.6 (q, J=3.8 Hz), 125.4
Synthesis of 1,2,3,4,5-penta(4-fluorophenyl)-1,3-cyclopentadiene (12c): A
solution of 1-bromo-4-fluorobenzene (1.01 g, 5.76 mmol) in THF (20 mL)
was added dropwise to a suspension of Mg turnings (0.14 g, 5.96 mmol)
in THF (10 mL), under an inert atmosphere. The resulting mixture was
stirred at RT for 2 h, followed by addition of 2,3,4,5-tetrakis(4-fluorphe-
nyl)cyclopentadienone (11c, 1.75 g, 3.84 mmol) in one portion. The reac-
tion mixture was allowed to stir for an additional 3 h, before LiAlH4
(1.00 g, 26.3 mmol) was added and the reaction was stirred overnight
(16 h). The reaction was quenched with saturated aqueous NH4Cl (3 mL)
and was diluted with H2O (30 mL). The diluted mixture was extracted
with CH2Cl2 (3ꢃ50 mL), and the combined organic phases were dried
over anhydrous MgSO4 and concen-
(q, J=3.8 Hz), 124.0 (q, J=272.3 Hz),
62.8 ppm;
CDCl3):
19F NMR
d=À62.57,
(400 MHz,
À62.63,
À62.74 ppm; MS (ESI-TOF): calcd for
C40H20F15À: 785.1331; found: 785.1337.
Synthesis of penta
fluoromethylphenyl)-1,3-cyclopentadiene (12d, 1.25 g, 1.59 mmol) and
[Ru3(CO)12] (0.41 g, 0.64 mmol) were dissolved in 2:1 mixture of
ACHTUNGTREN(UNNG p-CF3-Ph)CpRu(CO)2Cl (6): 1, 2, 3, 4, 5-Penta(4-tri-
a
decane/toluene (12 mL) in a dry screw-cap tube, under an inert atmos-
phere. The resulting mixture was stirred at 1608C for 2.5 days, followed
by addition of CHCl3 (1.5 mL, 18.6 mmol), and was allowed to stir at
1608C for an additional 1.5 h. Pentane (3 mL) was then added and the
mixture was filtered off to give a yellow solid. Further purification by
column chromatography (CH2Cl2) gave a yellow solid (0.38 g, 25%).
1H NMR (400 MHz, CDCl3): d=7.45 (dm, J=8.3 Hz, 10H), 7.12 ppm
(dm, J=8.0 Hz, 10H); 13C NMR (100 MHz, CDCl3): d=195.0, 132.2,
132.1 (q, J=1.5 Hz), 131.3 (q, J=33 Hz), 125.5 (q, J=3.7 Hz), 123.5 (q,
J=273 Hz), 105.5 ppm; 19F NMR (400 MHz, CDCl3): d=À62.9 ppm; IR
trated under reduced pressure to give
a pale purple solid. Purification of the
purple solid by column chromatogra-
phy (pentane/EtOAc 95:5) gave the
desired product as
a white solid
(1.15 g, 56%). Spectral data were in
accordance with those previously re-
ported in the literature.[16]
Synthesis of pentaACHTUNGTRENNUNG(p-F-Ph)CpRu-(CO)2Cl (5): 1,2,3,4,5-Penta(4-fluoro-
phenyl)-1,3-cyclopentadiene (12b, 0.50 g, 0.93 mmol) and [Ru3(CO)12]
(0.24 g, 0.37 mmol) were dissolved in a 2:1 mixture of decane/toluene
(6 mL) in a dry screw-cap tube, under an inert atmosphere. The resulting
mixture was stirred at 1608C for 2.5 days, followed by addition of CHCl3
(1.0 mL, 12.4 mmol), and was allowed to stir at 1608C for an additional
1.5 h. Pentane (3 mL) was then added and the mixture was filtered off to
(KBr): n˜ =2062, 2019, 1619, 1327 cmÀ1
; MS (ESI-TOF): calcd for
C42H20ClF15NaO2Ru+: 1000.9848; found: 1000.9800.
General procedure for racemization studies: Ruthenium catalyst 3, 4, 5,
or 6 (3.80 mmol) and Na2CO3 (0.38 mmol) were added to a flame-dried
microwave tube in a glove box. The solids were suspended in dry toluene
Chem. Eur. J. 2011, 17, 11216 – 11222
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11221

J.-E. Bꢁckvall et al.
(1.5 mL) and were allowed to stir for 5 min at RT. Potassium tert-butox-
ide (11.4 mmol) in THF (40 mL) was added, and a color change from
yellow to orange could be observed, indicating activation of the catalyst.
After stirring for 5–60 min (depending on the catalyst) at RT, 1-phenyl-
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Financial support from the European Research Council (ERC AdG
247014) is gratefully acknowledged.
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Received: March 17, 2011
Published online: August 31, 2011
11222
www.chemeurj.org
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 11216 – 11222