Catalytic asymmetric synthesis of cyclopentenones from propargyl malonates and allylic acetate by successive action of homogeneous palladium(II) and cobalt on charcoal catalysts in a one-pot reaction

Article abstract of DOI:10.1039/b106836a

The tandem action of a homogeneous chiral Pd(II) catalyst and a heterogeneous Co/C catalyst leads to a two-step one-pot highly enantioselective Pauson-Khand-type reaction.

Full text of DOI:10.1039/b106836a

View Article Online / Journal Homepage / Table of Contents for this issue
Catalytic asymmetric synthesis of cyclopentenones from propargyl
malonates and allylic acetate by successive action of homogeneous
palladium(II) and cobalt on charcoal catalysts in a one-pot reaction†
Seung Uk Son,a Kang Hyun Park,a Hwimin Seo,a Young Keun Chung*a and Sueg-Geun Leeb
a School of Chemistry and Center for Molecular Catalysis, Seoul National University, Seoul 151-747,
Korea. E-mail: ykchung@plaza.snu.ac.kr; Fax: (+82)2-889-0310; Tel: +82-2-880-6662
b Korea Research Institute of Chemical Technology, PO Box 107, Yusong, Taejeon 305-600, Korea
Received (in Cambridge, UK) 30th July 2001, Accepted 17th October 2001
First published as an Advance Article on the web 5th November 2001
The tandem action of a homogeneous chiral Pd(II) catalyst
and a heterogeneous Co/C catalyst leads to a two-step one-
pot highly enantioselective Pauson–Khand-type reaction.
ligands were effective for Pd-catalyzed asymmetric allylic
alkylation. The ee values of 4(Me) ranged from 83 to 95% at
room temperature. As expected, the best ligand was phosphino-
oxazoline ligand b. The best ee value of 96% was obtained
when the reaction was conducted at 0 °C in the presence of b
(entry 3 in Table 1). The absolute configuration of 3(Me) was
easily established by comparison of the observed [a] values
with those of the known reactions. The absolute configuration
(3R,4S,5R) of the bicyclic enone 4(Me) was determined by an
NMR study. When the reaction in Scheme 1 was carried out
stepwise to determine whether the ee value was changed during
the carbonylative cyclization, the ee value of the final product
was the same as that of the first step and no other diastereomer
was found in the second step. Thus, the ee value of the first
asymmetric allylic alkylation reaction was maintained during
the second cycloaddition reaction. This suggests that the first
step is a stereoselective reaction and the second a stereospecific
one. The enantioselectivity of this tandem cycloaddition was
absolutely dependent on the Pd-catalyzed asymmetric allylic
alkylation. This could be a good advantage of this combination
of catalysts because the palladium-catalyzed allylic alkylation is
one of the most thoroughly and intensively studied catalytic
transformations. High yields were observed for all reactions.
The yield of the second step was always quantitative. Thus, the
turnover number was completely dependent upon the Pd-
catalyzed allylic alkylation. For convenience, we used 2.5
mol% of Pd(II) catalyst for studying the reactions.
Much success has been achieved in the field of transition-metal-
mediated (or catalyzed) synthesis of cyclopentenones from
readily available substrates;1 however, catalytic asymmetric
synthesis is still surprisingly underdeveloped. The use of a
chiral titanocene complex (EBTHI)Ti(CO)2 (EBTHI = ethyl-
5
ene-1,2-bis(h -4,5,6,7-tetrahydroinden-1-yl)2 and Co,3 Rh,4
and Ir5 complexes with chiral diphosphines have been recently
reported. Demand for the development of a catalytic and
enantioselective Pauson–Khand type reaction remains high.
Recently, the tandem use of two kinds of homogeneous
catalyst in a one-pot multistep transformation of substrates to
products has been reported.6 The report by Jeong’s group has
attracted our attention. They used a combination of Pd and Rh
catalysts in the preparation of bicyclopentenones from propa-
rgyl malonates. The use of Pd-catalyzed asymmetric allylic
alkylation7 to generate enantioselective enynes appears to be
quite promising. However, the use of in situ generated
enantiomerically enriched enynes as substrates in the Pauson–
Khand reaction has not been reported even though increasing
efforts are being devoted to the development of practical
enantioselective versions of the Pauson–Khand reaction.8
In this connection, we decided to use the Pd(II)-catalyzed
asymmetric allylic alkylation in the synthesis of enantiomer-
ically pure enynes. We report herein that the tandem action of
homogeneous chiral Pd(II) catalyst and heterogeneous catalyst
Co/C9 leads to a ‘two-step one-pot’ highly enantioselective
Pauson–Khand-type reaction. The efficiency of this two-step
one-pot reaction was studied for 3(Me) as shown in Scheme 1.
Thus, we screened several chiral ligands (Chart 1) to find the
best chiral ligand (Table 1).10 The same reaction was conducted
in the presence of dppe to obtain racemic products. All the chiral
The success of this tandem catalytic reaction is primarily due
to the use of Co/C. In the Pd(II)-catalyzed allylic alkylation
reaction, acetic acid was generated. The acid would interact
with cobalt species in the solution. When Co2(CO)8 (20 mol%)
instead of Co/C was used as a catalyst, only 2% of the product
Chart 1
Table 1 Asymmetric one-pot synthesis of bicyclopentenonea
Entry
Chiral ligand
Time/hb
Yield (%)c
Ee (%)d
1
2
3e
4f
5
a
b
b
b
c
10
4
18
4
74
81
95
2
—
95
96
—
83
12
81
a 1a and 2a used as substrates. Conditions for the 2nd step: 130 °C, 18 h, 30
atm. CO.b Reaction time of the first step at rt.c Isolated yield.d Diacel OD
column was used.e Reaction temperature of the first step is 0 °C.f 20 mol%
Co2(CO)8 was used instead of Co/C.
Scheme 1
† Electronic supplementary information (ESI) available: experimental
details. See http://www.rsc.org/suppdata/cc/b1/b106836a/
2440
Chem. Commun., 2001, 2440–2441
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b106836a

View Article Online
Table 2 Asymmetric one-pot synthesis of various cyclopentenonesa
synthesis of various tricyclic enones 6(n) (n = 1–3) (Scheme 2
and entries 4–6 in Table 2).
Time/ Yield Ee
The intramolecular Pauson–Khand reaction of cyclic enynes
having cyclopentenes or cyclohexenes with pendant alkynes has
been well studied.11 Chiral ligand d developed by Trost12 was
selected since it is one of the best ligands in the Pd(II)-catalyzed
asymmetric reaction of 2-cyclopentenyl, -hexenyl, or -hepenyl
acetate with the anion of dimethyl malonate.13 The reaction was
quite sensitive to the base and the solvent used. The best results
were obtained when Cs2CO3 and dichloromethane were used as
a base and a solvent, respectively.13 Interestingly, substrates
5(2) and 5(3) were known not to be cyclized with (EBTHI)-
Ti(CO)2.1 However, fairly high yields (89–97%) were obtained
in our case. In the cyclization of 5(1), the reduced 7 was
obtained as a byproduct provided the generated acetic acid was
not removed. In contrast to the high yields, the ee values
(31–94%) were quite sensitive to the ring size. As the ring size
increases, the ee values decrease. A fairly high ee value of 94%
was obtained for 6(1). The absolute configuration (3R,4R,5S) of
the tricyclic enone 6(n) was determined by comparison with the
known reactions.13 The fused tricyclic systems such as 6(1) and
6(2) had been used in the synthesis of natural products.14
In summary, we have demonstrated that the tandem action of
a homogeneous chiral Pd(II) catalyst and a heterogeneous Co/C
catalyst leads to a two-step one-pot highly enantioselective
Pauson–Khand-type reaction. The enantiomeric purity of the
product depends upon the optical purity of the in situ generated
enyne. Further synthetic applications of the tandem action of
two different catalysts in other reactions are now in progress.
This work supported by the Korea Science and Engineering
Foundation (KOSEF) (1999-1-122-001-5), and the KOSEF
through the Center for Molecular Catalysis. SUS, KHP, and HS
acknowledge receipt of the BK21 fellowship.
Substrates
Product
L*
Base
BSA
hb
(%)c (%)d
1
2
3
1a 2a
b
4
81
95
84
95
84
93
1b 2a
1c 2a
b
b
BSA
BSA
6
4
4
5
1a 2b
1a 2c
a
d
d
BSA
BSA
CS2CO3 12
10
24
95
85
92
—
33
94
e
a
d
d
BSA
BSA
Cs2CO3 12
10
24
95
90
90
—
36
72
e
6
1a 2d
a
d
d
BSA
BSA
Cs2CO3 12
10
24
89
93
97
—
4
31
e
Notes and references
3
a Reaction conditions: 6.0 mol% L* , 2.5 mol% [(h allyl)PdCl]2, 0.2 g Co/
C, and THF. Condtions for the 2nd step: 130 °C, 18 h, and 30 atm
CO.b Reaction time of the first step at rt.c Isolated yield.d Diacel OD column
was used.e CH2Cl2 as a solvent.
1 For recent reviews, see: N. Jeong, in Transition Metals in Organic
Synthesis, ed. M. Beller and C. Bolm, Wiley-VCH, Weinheim, 1998,
vol. 1, p. 560; Y. K. Chung, Coord. Chem. Rev., 1999, 188, 297; K. M.
Brummond and J. L. Kent, Tetrahedron, 2000, 56, 3263.
2 F. A. Hicks and S. L. Buchwald, J. Am. Chem. Soc., 1996, 118,
11688.
3 K. Hirori, T. Watanabe, R. Kawagishi and I. Abe, Tetrahedron Lett.,
2000, 41, 891.
4 N. Jeong, B. K. Sung and Y. K. Choi, J. Am. Chem. Soc., 2000, 122,
6771.
was isolated (entry 4 in Table 1). However, the Co/C was found
to be insensitive to acid or base. Generally, for good
enantioinduction, low temperatures are required. However, our
reaction conditions in the second step seem to be quite harsh,
nevertheless no racemization occurred under these reaction
conditions. We also examined the catalytic asymmetric carbo-
nylative cyclization of 3(R) (R = Ph, n-Bu) (entries 2 and 3 in
Table 2). Under our reaction conditions, 4(R) were obtained in
high yields (84–95%) with high ee values (84–95%). The
usefulness of this combination catalyst is highlighted by the
5 T. Shibata and K. Takagi, J. Am. Chem. Soc., 2000, 122, 9852.
6 R. W. Barnhart and G. C. Bazan, J. Am. Chem. Soc., 1998, 120, 1082;
Z. J. A. Komon, X. Bu and G. C. Bazan, J. Am. Chem. Soc., 2000, 122,
1830; N. Jeong, S. D. Seo and J. Y. Shin, J. Am. Chem. Soc., 2000, 122,
10220; P. A. Evans and J. E. Robinson, J. Am. Chem. Soc., 2001, 123,
4609.
7 B. M. Trost and D. L. van Vranken, Chem. Rev., 1996, 96, 395.
8 X. Verdaguer, J. Vázquez, G. Fuster, V. Bernardes-Génisson, A. E.
Greene, A. Moyano, M. A. Pericàsa and A. Riera, J. Org. Chem., 1998,
63, 7037; J. Castro, A. Moyano, M. A. Pericàsa, A. Riera, A. Alvarez-
Larena and J. F. Piniella, J. Am. Chem. Soc., 2000, 122, 7944.
9 S. U. Son, S.-I. Lee and Y. K. Chung, Angew. Chem., Int. Ed., 2000, 39,
4158.
10 P. Von Matt and A. Pfaltz, Angew. Chem., Int. Ed. Engl., 1993, 32, 566;
J. Sprinz and G. Helmchen, Tetrahedron Lett., 1993, 34, 1769; G. J.
Dawson, C. G. Frost, J. M. J. Williams and S. J. Coote, Tetrahedron
Lett., 1993, 34, 3149.
11 C. Almansa, A. Moyano and F. Serratosa, Tetrahedron, 1988, 44, 2657;
J. Macro-Contelles and J. Ruiz, Tetrahedron Lett., 1998, 39, 6393; J.
Cassayre and S. Z. Zard, J. Organomet. Chem., 2001, 624, 316.
12 B. M. Trost, D. L. van Vranken and C. Bingel, J. Am. Chem. Soc., 1992,
114, 9327.
13 B. M. Trost and R. C. Bunt, J. Am. Chem. Soc., 1994, 116, 4089; B. M.
Trost and R. C. Bunt, Angew. Chem., Int. Ed. Engl., 1996, 35, 99.
14 S. Takano, K. Inomata and K. Ogasawara, Chem. Lett., 1992, 443; L. A.
Paquette and S. Borrelly, J. Org. Chem., 1995, 60, 6912; J. Cassayre and
S. Z. Zard, J. Am. Chem. Soc., 1999, 121, 6072.
Scheme 2
Chem. Commun., 2001, 2440–2441
2441