Rh(I)-Catalyzed Asymmetric Intramolecular Pauson-Khand Reaction in Aqueous Media

Article abstract of DOI:10.1055/s-2003-41044

The first rhodium-BINAP complex-catalyzed enantioselective Pauson-Khand reaction in aqueous media, which is accelerated by surfactant, is reported. The chiral rhodium catalyst is easily prepared in situ from 1 equivalent of [Rh(cod)Cl]₂ and 2 e

Full text of DOI:10.1055/s-2003-41044

PAPER
2169
Rh(I)-Catalyzed Asymmetric Intramolecular Pauson–Khand Reaction in
Aqueous Media
Rh(I)-Catalyzed
A
symm
o
etric Intram
n
olecula
r
Pauson–K
H
handReaction in
A
y
queous
M
ed
u
ia ck Suh, Mira Choi, Sang Ick Lee, Young Keun Chung*
School of Chemistry and Center for Molecular Catalysis, Seoul National University, Seoul 151-747, Korea
Fax +82(2)8890310; E-mail: ykchung@plaza.snu.ac.kr
Received 20 May 2003; revised 1 July 2003
fore, our first reactions were designed to study the effect
of the co-solvent on the rhodium-catalyzed Pauson–
Khand reaction without using activators. The co-solvent
used ranged from non-polar hexane to ionic liquid
Abstract: The first rhodium-BINAP complex-catalyzed enantiose-
lective Pauson–Khand reaction in aqueous media, which is acceler-
ated by surfactant, is reported. The chiral rhodium catalyst is easily
prepared in situ from 1 equivalent of [Rh(cod)Cl]2 and 2 equivalents
of BINAP under 1 atm of CO and a temperature of 60 °C or 90 °C. (Table 1). Our solvent of choice for further studies was a
Ee’s up to 96% were achieved for the intramolecular Pauson–
mixture of 1,4-dioxane–water in a ratio of 1:1. When the
Khand reaction, but the yields are highly dependent upon the sub-
strate itself.
ratio was altered from 1:1, both the yield and enantiose-
lectivity dropped. We also studied the effect of the reac-
tion temperature on both the yield and ee values. We
found the optimum temperature to be 90 ºC. Since surfac-
Key word: Pauson–Khand reaction, rhodium, BINAP, surfactant,
aqueous
tants are known to induce reactions in aqueous phase to
proceed smoothly,3 we introduced a surfactant such as
Recently, tremendous attention has been given to aqueous
phase reactions as a consequence of the increasing de-
mand for efficient, safe, and environmentally friendly
processes.1 These aqueous systems can offer a fruitful op-
portunity for the practice of green chemistry. Extensive
research on new and effective catalytic Pauson–Khand re-
actions has continued to yield ever more efficient methods
for the preparation of cyclopentenone compounds.2 How-
ever, in spite of the recent demand for the development of
more environmentally benign processes, the application
of homogeneous catalysts in aqueous solution and on liq-
uid supports is still quite rare.3 Previously, water was em-
ployed as a Lewis base promoter in the Pauson–Khand
reaction.4 Recently, the first intramolecular Pauson–
Khand reaction in water was carried out by using aqueous
colloidal cobalt nanoparticles as catalysts.5 However, the
reaction was not asymmetric. Thus, the usefulness of the
catalytic system was diminished. In these circumstances,
we focused our attention on studying the use of water as a
co-solvent or the sole solvent in the rhodium-catalyzed
asymmetric Pauson–Khand reaction. Herein we report the
first use of a rhodium catalyst in an asymmetric Pauson–
Khand reaction in aqueous media.
cetyltrimethylammonium bromide (CTAB) and sodium
dodecylsulfate (SDS) as an additive. Interestingly, the use
of the surfactant as an additive had an influence on the re-
action time. When a cationic surfactant CTAB was used,
the reaction time increased to 24 hours with a slightly de-
creased enantioselectivity (62% yield; 77% ee). However,
when an anionic surfactant SDS was used, the reaction
time was reduced to 1.5 hours with almost no change in
the enantioselectivity. However, the reaction rate was
rather insensitive to the amount of SDS used. Thus, we
Table 1 Rh(I)-Catalyzed Asymmetric Pauson–Khand Reaction in
Various Solventsa
Entry
Solvent
1,4-dioxane
1,4-dioxane
THF
Time (h) Ee (%)
Yield (%)
1
2b
3
4
5
6
7
8
1.5
12
85
86
81
57
46
70
79
42
70
88
87
45
37
46
75
56
We first investigated the effect of the solvent system on
the rhodium-catalyzed Pauson–Khand reaction. A combi-
nation of [Rh(cod)Cl]2 and BINAP was chosen as a cata-
lyst for an asymmetric Pauson–Khand reaction because
this system was one of the best catalytic systems for an
asymmetric intramolecular Pauson–Khand reaction in
THF.6a When a Pauson–Khand reaction was carried out in
a water solution, no reaction was observed presumably
due to the insolubility of the substrate and catalyst. There-
3
26
24
24
15
9
DME
Hexane
c
[bmin]PF6
toluene
CH2Cl2
a Conditions: 3 mol% [Rh(cod)Cl]2 (25 mg), 6 mol% BINAP (63 mg),
6 mol% SDS (29 mg), solvent–H2O, 1:1, 90 °C.
b Without surfactant.
Synthesis 2003, No. 14, Print: 02 10 2003. Web: 28 08 2003.
Art Id.1437-210X,E;2003,0,14,2169,2172,ftx,en;F04603SS.pdf.
DOI: 10.1055/s-2003-41044
c Ionic liquid.
© Georg Thieme Verlag Stuttgart · New York

2170
W. H. Suh et al.
PAPER
temporarily established optimized reaction conditions as within a short time, then the ee of the product might be
follows, 1,4-dioxane–H2O, 1:1; 6 mol% of SDS; 3 mol% high. A prolonged reaction time might result in a poor ee
of [Rh(cod)Cl]2; 6 mol% of BINAP; 90 ºC (1.5 h); and value.
1atm CO.
In summary, this study constitutes the first demonstration
Before proceeding to other substrates, we screened rhodi- that both asymmetric and heterogeneous versions can be
um complexes in order to confirm that the rhodium cata- achieved at the same time in the presence of surfactants.
lyst chosen for this study was the best (Table 2).
Table 3 Rh(I)-Catalzyed Pauson–Khand Reaction in Aqueous Me-
As shown in Table 2, considering both the yield and ee
values, [Rh(cod)Cl]2 was the best choice.
dia for Various Substrtatesa
Entry
1
Substrate
Yield (%)
70
ee (%)
85
Table 2 Various Rh-Catalyzed Asymmetric Pauson–Khand Reac-
tion in Aqueous Mediaa
Entry
Catalyst
Yield (%)
ee (%)
85
2
N.R
–
1
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)2]BF4
Rh(acac)(CO)2
70
88
15
16
2b
3
81
3
4
5
30
32
55
88
96
68
88
4
58
a H2O–1,4-dioxane (1:1), 6 mol% of SDS, 3 mol% of [Rh(cod)Cl]2, 6
mol% of BINAP, 90 ºC, and 1.5 h.
b 3 mol% of [Rh(cod)Cl]2, 6 mol% of (S)-BINAP, 12 mol% of AgO-
Tf, 90 °C in THF 3 h.
Ar = 2-naphthyl
Other enynes were subjected to the optimized reaction
conditions (Table 3). Relatively high enantioselectivities
(68–96%) were achieved, but the yields varied depending
upon the substrate. When the acetylenic substituent was
butyl or methyl (entries 3 and 4), high ee values and poor
yields were obtained. As the steric bulkiness of the sub-
stituent on the alkyne increases (entries 1, 5, 6, and 9–11),
the ee values and yields decreased. The electronic effect
of the substituent was not as apparent as the steric effect.
An electron-donating substituent is more helpful than an
electron-accepting substituent (entries 7 and 8). When
substrates having the same skeleton with a different bridg-
ing atom (entries 4, 10, and 12) were compared, the best
conversion yield (86%) was obtained for a nitrogen-teth-
ered enyne and the best ee (96%) was obtained for an ox-
ygen-tethered enyne. The internal alkene (entry 2) was
inactive in our reaction condition.
6
7
8
64
65
43
67
91
84
Ar = 3,5-dimethylphenyl
Ar = 4-methoxyphenyl
Ar = 4-Bromophenyl
9
10
11
86
93
37
93
71
86
After work-up, we could isolate a yellow crystalline solid
that was found to be a rhodium phosphine monoxide
[Rh{BINAP(O)}] complex by single crystal X-ray dif-
fraction study.7 During the reaction, the rhodium complex
might be oxidized by water to give [Rh{BINAP(O)}]
complex. In the beginning, we suspected that [Rh{BI-
NAP(O)}] was a catalyst in the reaction. However, when
a newly synthesized-[Rh{BINAP(O)}] was used as a cat-
alyst, a racemate was obtained in a 10% yield and approx-
imately 80% of the reactant was recovered. When bis-
a H2O–1,4-dioxane (1:1), 6 mol% of SDS, 3 mol% of [Rh(cod)Cl]2, 6
mol% of BINAP, 90 ºC, 1.5 h.
All reactions were conducted under nitrogen using standard
Schlenk-type flasks. Work-up procedures were done in air. All sol-
vents were dried and distilled according to standard methods before
phosphine monoxide rhodium [Rh{BINAP(O)2}] com- use. Reagents were purchased from Aldrich Chemical Co., Acros
Chemical Co. and were used as received. BINAP was purchased
plex was generated in situ by addition of [Rh(cod)Cl]2
from Strem. IR spectra were obtained in solution or measured as
with BINAP(O)2, no reaction was observed. These results
films on NaCl by evaporation of solvent. 1H NMR spectra were ob-
tained with a Bruker 300 spectrometer. High Resolution Mass spec-
trum was measured at the Korea Basic Science Institute(Daegu).
The ee’s were determined by chiral HPLC analysis. For entries 1,
unambiguously prove that the relative ratio of rhodium
and rhodium phosphine monoxide determines the ee of
the reaction product. Thus, if a reaction was completed
Synthesis 2003, No. 14, 2169–2172 © Thieme Stuttgart · New York

PAPER
Rh(I)-Catalyzed Asymmetric Intramolecular Pauson–Khand Reaction in Aqueous Media
2171
3–8, a CHIRALPAK AS: 4 × 250mm, 254 nm UV detector (Daicel
Chemical Ind., Ltd) was used. For entries 9–11, a CHIRALPAK
AD (Daicel Chemical Ind., Ltd) was used.
1-[3-(Allyloxy)prop-1-yn-1-yl]-3,5-dimethylbenzene (entry 6 in
Table 3)
1H NMR (CDCl3, 300 MHz): = 2.27 (s, 6 H), 4.13 (d, J = 5.8 Hz,
2 H), 4.36 (s, 2 H), 5.23 (dd, J = 10.4, 10.4 Hz, 1 H), 5.34 (dd, J =
17.2, 17.2 Hz, 1 H), 5.90 (m, 1 H), 6.94 (s, 1 H), 7.08 (s, 2 H).
Asymmetric Pauson–Khand Reaction with Rhodium–BINAP
Complex in Aqueous Media; General Procedure
13C NMR (CDCl3, 125 MHz): = 21.5, 58.3, 71.0, 84.6, 87.0, 118.3,
122.6, 129.8, 130.7, 134.4, 138.2.
To a Shclenck-type flask charged with [Rh(cod)Cl]2 (25 mg, 0.05
mmol) and (S)-BINAP (63 mg, 0.1 mmol) was added solvent (1
mL). After the solution was stirred at r.t. for 20 min, a balloon filled
with CO was attached to the flask with stirring. After 20 min, enyne
(1.5 mmol), SDS, and H2O (2 mL) were added. The resulting solu-
tion was heated at 90 ºC for 1.5 h. After the solution was cooled to
r.t., CH2Cl2 (10 mL) was added. Removal of water over anhydrous
MgSO4 followed by chromatography on a silica gel column eluting
with hexane–diethyl ether gave the product.
HRMS: m/z calcd for C14H16O, 200.1201; found, 200.1205.
6-(3,5-Dimethylphenyl)-3a,4-dihydro-1H-cyclopenta[c]furan-
5(3H)-one (entry 6 in Table 3)
Yield: 64%; ee 67%; major isomer: tR 8.8 min, minor isomer: tR 10.8
min (10% 2-propanol–hexane, flow rate: 1.0 mL/min).
IR: 1705 cm-1 (C=O).
1H NMR (CDCl3, 300 MHz): = 2.28 (d, J = 12.4 Hz, 1 H), 2.34 (s,
6 H), 2.84 (dd, J = 6.1, 6.0 Hz, 1 H), 3.22 (dd, J = 11.1, 11.2 Hz, 1
H), 3.29 (m, 1 H), 4.38 (t, J = 7.1 Hz, 1 H), 4.58 (d, J = 16.3 Hz, 1
H), 4.94 (d, J = 16.6 Hz, 1 H), 7.00 (s, 1 H), 7.17 (s, 2 H).
13C NMR (CDCl3, 125 MHz): = 21.8, 40.7, 43.6, 66.7, 71.7, 120.3,
126.1, 135.4, 138.5, 177.6, 207.5.
A general procedure for Synthesis of Entries 5,6,7 and 8; Typi-
cal Procedure
To a solution of 4-arene-2-yn-1-ol (5 mmol)8 and anhyd DMF(30
mL), was added NaH (60% in oil, 1.2 equiv) at 0 °C. After 1h, allyl
bromide was added at 0 °C, and the mixture was allowed to warm
to r.t. and stirred. After 2 h, the mixture was cautiously quenched
with saturated aqueous NaCl (20 mL)and extracted with Et2O (30
mL). The ethereal solution was dried with MgSO4, purified by flash
column chromatography to afford the product.
HRMS: m/z calcd for C15H16O2, 228.1150; found, 228.1148.
6-(4-Methoxyphenyl)-3a,4-dihydro-1H-cyclopenta[c]furan-
5(3H)-one (entry 7 in Table 3)
Yield: 64%; ee 67%; major isomer: tR 16 min, minor isomer: tR 28
min (10% 2-propanol–hexane, flow rate: 1.0 mL/min); spectral data
were consistent with those in literature.6b
2-Phenyl-7-oxabicyclo[3.3.0]oct-1-en-3-one (entry 1 in Table 3)
Yield: 70%; ee 85%; R-isomer: tR 18 min, S-isomer tR 25 min (10%
2-propanol–hexane, flow rate: 1.0 mL/min); spectral data were con-
sistent with those in the literature.6a
1-[3-(Allyloxy)prop-1-yn-1-yl]-4-bromobenzene (entry 8 in Ta-
ble 3)
2-Butyl-7-oxabicyclo[3.3.0]oct-1-en-3-one (entry 3 in Table 3)
Yield: 30%; ee 88%; major isomer: tR 12 min, minor isomer: tR 14
min (10% 2-propanol–hexane, flow rate: 1.0 mL/min); spectral data
were consistent with those in the literature.6a
1H NMR (CDCl3, 300 MHz): = 4.12 (dd, J = 1.2, 1.2 Hz, 2 H),
4.35 (s, 2 H), 5.24 (dd, J = 10.2, 10.4 Hz, 1 H), 5.34 (dd, J = 17.2,
17.4 Hz, 1 H), 7.43 (d, J = 8.7 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): = 58.7, 71.2, 85.5, 86.6, 118.5,
121.9, 123.1, 131.9, 133.6, 134.2. HRMS: m/z calcd for C12H11OBr,
249.9993, found, 249.9996.
2-Methyl-7-oxabicyclo[3.3.0]oct-1-en-3-one (entry 4 in Table 3)
Yield: 32%; ee 96; major isomer: tR 17 min, minor isomer: tR 23 min
(210 nm, 10% 2-propanol–hexane, flow rate: 1.0 mL/min); spectral
data were consistent with those in the literature.6a
6-(4-Bromophenyl)-3a,4-dihydro-1H-cyclopenta[c]furan-
5(3H)-one (entry 8 in Table 3)
Yield: 43%; ee 84%; major isomer: tR 8.8 min, minor isomer: tR 10.8
min (10% 2-propanol–hexane, flow rate: 1.0 mL/min).
2-[3-(Allyloxy)prop-1-yn-1-yl]naphthalene (entry 5 in Table 3)
1H NMR (CDCl3, 300 MHz): = 4.17 (d, J = 5.8 Hz, 2 H), 4.42 (s,
2 H), 5.35 (dd, J = 10.4, 10.4 Hz, 1 H), 5.38 (dd, J = 17.2, 17.2 Hz,
1 H), 5.90 (m, 1 H), 7.48 (m, 3 H), 7.78 (m, 3 H), 7.97 (s, 1 H).
IR: 1705cm–1 (C=O).
13C NMR (CDCl3, 125 MHz): = 53.5, 58.0, 70.7, 85.4, 86.6, 117.9,
119.9, 126.6, 126.7, 127.7, 128.0, 128.4, 131.7, 132.8, 134.0.
1H NMR (CDCl3, 300 MHz): = 2.34 (dd, J = 17.7, 17.9 Hz, 1 H),
2.84 (dd, J = 5.6, 6.0 Hz, 1 H), 3.24 (dd, J = 7.0, 7.2 Hz, 1 H), 3.30
(m, 1 H), 4.38 (t, J = 6.9 Hz, 1 H), 4.55 (d, J = 16.5 Hz, 1 H), 4.91
(d, J = 16.4 Hz, 1 H), 7.41 (d, J = 8.8 Hz, 2 H), 7.52 (d, J = 8.9 Hz,
1 H).
13C NMR (CDCl3, 125 MHz): = 40.6, 43.8, 66.6, 71.6, 123.2,
129.8, 129.9, 132.2, 133.9, 178.5, 206.9.
HRMS: m/z calcd for C16H14O, 222.1044; found, 222.1042.
6-(2-Naphthyl)-3a,4-dihydro-1H-cyclopenta[c]furan-5(3H)-one
(entry 5 in Table 3)
Yield: 55%; ee 68%; major isomer: tR 14.9 min, minor isomer: tR 17
min (10% 2-propanol–hexane, flow rate: 1.0 mL/min).
HRMS: m/z calcd for C12H11OBr, 277.9942; found, 277.9943.
IR: 1705 cm–1 (C=O).
1H NMR (CDCl3, 300 MHz): = 2.34 (dd, J = 17.5 Hz, 1 H), 2.83
(dd, J = 5.6, 6.0 Hz, 1 H), 3.24 (dd, J = 7.0, 7.2 Hz, 1 H), 3.4 (m, 1
H), 4.34 (t, J = 6.9 Hz, 1 H), 4.59 (d, J = 16.5 Hz, 1 H), 4.98 (d, J =
16.4 Hz, 1 H), 7.48 (m, 3 H), 7.81 (m, 3 H), 8.10 (s, 1 H).
13C NMR (CDCl3, 125 MHz): = 23.1, 32.0, 40.8, 66.8, 71.7, 125.8,
126.2, 126.8, 127.1, 128.0, 128.1, 128.4, 128.6, 128.9, 133.4, 133.6,
134.9, 178.2, 207.4.
6-Methyl-2-(toluene-4-sulfonyl)-2,3,3a,4-tetrahydro-1H-cyclo-
penta[c]pyrrol-5(3H)-one (entry 9 in Table 3)
Yield: 86%; ee 93%; major isomer: tR 26 min, minor isomer: tR 30
min (10% 2-propanol–hexane, flow rate: 1.0 mL/min); spectral data
were consistent with those in the literature.6a
6-Phenyl-2-(toluene-4-sulfonyl)-2,3,3a,4-tetrahydro-1H-cyclo-
penta[c]pyrrol-5(3H)-one (entry 10 in Table 3)
Yield: 93%; ee 71%; major isomer: tR 17 min, minor isomer: tR 23
min (10% 2-propanol–hexane, flow rate: 1.0 mL/min); spectral data
were consistent with those in the literature.6a
HRMS: m/z calcd for C17H14O2, 250.0993; found, 250.0993.
Synthesis 2003, No. 14, 2169–2172 © Thieme Stuttgart · New York

2172
W. H. Suh et al.
PAPER
(3) Very recently an aqueous-phase stoichiometric Pauson–
Khand reaction was reported, see: Kraft M. E., Wright J. A.,
Boaga L. V. R.; Tetrahedron Lett.; 2003, 44: 3417.
(4) (a) Sugihara, T.; Yamaguchi, M.; Nishizawa, M. Chem.–
Eur. J. 2001, 7, 1589. (b) Sugihara, T.; Yamaguchi, M.
Synlett 1998, 1384.
Diethyl 6-Methyl-5-oxo-3,3a,4,5-tetrahydropentalene-2,2(1H)-
dicarboxylate (entry 11 in Table 3)
Yield: 37%; ee 86%; major isomer: tR 26 min, minor isomer: tR 30
min (10% 2-propanol–hexane, flow rate: 1.0 mL/min); spectral data
were consistent with those in the literature.6a
(5) Son, S. U.; Lee, S. I.; Chung, Y. K.; Kim, S.-W.; Hyeon, T.
Org. Lett. 2002, 4, 277.
Acknowledgments
(6) For Rh see: (a) Jeong, N.; Sung, B. K.; Choi, Y. K. J. Am.
Chem. Soc. 2000, 122, 6771. (b) For Ir see: Shibata, T.;
Takagi, K. J. Am. Chem. Soc. 2000, 122, 9852. (c) For Ti
see: Hick, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996,
118, 11688. (d) For Co see: Sturla, S. J.; Buchwald, S. L. J.
Org. Chem. 2002, 67, 3398. (e) Hiroi, K.; Watanabe, T.;
Kawagishi, R.; Abe, I. Tetrahedron Lett. 2000, 41, 891.
(7) The same crystal structure was reported by Poe et al., see:
Bunten, K. A.; Farrar, D. H.; Poe, A. J.; Lough, A.
Organometallics 2002, 21, 3344.
YKC thanks KOSEF for financial support (R01-1999-000-00041-
012002) and the KOSEF through the Center for Molecular Catalysis
at Seoul National University and MRC and SIL acknowledge re-
ceipt of the Brain Korea 21 fellowship.
References
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Synthesis 2003, No. 14, 2169–2172 © Thieme Stuttgart · New York