Rhodium complex-catalyzed Pauson-Khand-type reaction with aldehydes as a CO source

Article abstract of DOI:10.1021/jo0262661

With aldehydes as a CO source under solvent-free conditions, rhodium complex efficiently catalyzed an intramolecular carbonylative alkene-alkyne coupling (Pauson-Khand-type reaction) and various bicyclic enones were obtained in high yield. Experiments und

Full text of DOI:10.1021/jo0262661

Rh od iu m Com p lex-Ca ta lyzed P a u son -Kh a n d -Typ e Rea ction w ith
Ald eh yd es a s a CO Sou r ce
Takanori Shibata,* Natsuko Toshida, and Kentaro Takagi
Department of Chemistry, Faculty of Science, Okayama University, Tsushima, Okayama 700-8530, J apan
tshibata@cc.okayama-u.ac.jp
Received J uly 31, 2002
With aldehydes as a CO source under solvent-free conditions, rhodium complex efficiently catalyzed
an intramolecular carbonylative alkene-alkyne coupling (Pauson-Khand-type reaction) and various
bicyclic enones were obtained in high yield. Experiments under argon flow and a 13C-labeling
experiment suggested that almost no free carbon monoxide was generated in this reaction. When
noncationic rhodium complex with chiral phosphine was used as a chiral catalyst, the reaction
proceeded enantioselectively to give various chiral cyclopentenones in up to 90% ee under solvent-
free conditions.
In tr od u ction
studied since the 1960s, in the early stage of organome-
tallic chemistry.10 Rh complexes are effective catalysts11
and catalytic decarbonylation under mild reaction condi-
tions is still an intriguing topic.12 While the use of a
decarbonylative step in synthetic procedures, including
total syntheses, has already been reported,13 the syn-
thetic utilization of the generated carbon monoxide has
been largely ignored.14 In this study, we noted that
decarbonylation and Pauson-Khand-type reactions can
be catalyzed by the same transition metal (Rh) complex,
and that if two catalytic cycles of decarbonylation and
carbonylation occur in concert, the carbon monoxide
generated by the decarbonylation of aldehyde can be
efficiently used as a CO source for Pauson-Khand-type
reactions (Figure 1).
The transition metal-catalyzed carbonylative reaction
is one of the major procedures for preparing carbonyl
compounds. Carbonylative alkene-alkyne coupling (Pau-
son-Khand-type reaction) has drawn particular atten-
tion1 and various transition metal complexes (Co,1c,2 Ti,3
Ru,4 Rh5 complexes) have been reported as efficient
catalysts. Since the first reaction with a chiral Ti
complex,6 several highly enantioselective Pauson-Khand-
(-type) reactions have been reported with chiral Ir,7 Rh,8
and Co9 complexes. On the other hand, transition metal-
mediated and -catalyzed decarbonylation from carbonyl
compounds is a fundamental process and has been closely
* Address correspondence to this author. Fax: +81-86-251-7831.
(1) Recent reviews of the Pauson-Khand(-type) reaction: (a) Schore,
N. E. In Comprehensive Organometallic Chemistry II; Hegedus, L. S.,
Ed.; Pergamon: Oxford, UK, 1995; Vol. 12, pp 703-739. (b) Geis, O.;
Schmalz, H. G. Angew. Chem., Int. Ed. 1998, 37, 911-914. (c) J eong,
N. In Transition Metals In Organic Synthesis; Beller, M., Bolm, C.,
Eds.; Wiley-VCH: Weinheim, Germany, 1998; Vol. 1, pp 560-577.
(2) Recent examples: (a) J eong, N.; Hwang, S. H. Angew. Chem.,
Int. Ed. 2000, 39, 636-638. (b) Kim, S.-W.; Son, S. U.; Lee, S. I.; Hyeon,
T.; Chung, Y. K. J . Am. Chem. Soc. 2000, 122, 1550-1551. (c) Comely,
A. C.; Gibson, S. F.; Stevenazzi, A.; Hales, N. J . Tetrahedron Lett. 2001,
42, 1183-1185. (d) Sugihara, T.; Yamaguchi, M.; Nishizawa, M. Chem.
Eur. J . 2001, 7, 1589-1595. (e) Krafft, M. E.; Bon˜aga, L. V. R.;
Hirosawa, J . J . Org. Chem. 2001, 66, 3004-3020 and references
therein.
(3) (a) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J . Am. Chem.
Soc. 1996, 118, 9450-9451. (b) Hicks, F. A.; Kablaoui, N. M.; Buchwald,
S. L. J . Am. Chem. Soc. 1999, 121, 5881-5898.
(4) (a) Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J . Org.
Chem. 1997, 62, 3762-3765. (b) Kondo, T.; Suzuki, N.; Okada, T.;
Mitsudo, T. J . Am. Chem. Soc. 1997, 119, 6187-6188.
(5) (a) Koga, Y.; Kobayashi, T.; Narasaka, K. Chem. Lett. 1998, 249-
250. (b) J eong, N.; Lee, S.; Sung, B. K. Organometallics 1998, 17, 3642-
3644. (c) Kobayashi, T.; Koga, Y.; Narasaka, K. J . Organomet. Chem.
2001, 624, 73-87. (d) J eong, N.; Sung, B. K.; Choi, Y. K. J . Am. Chem.
Soc. 2000, 122, 6771-6772. (e) Evans, P. A.; Robinson, J . E. J . Am.
Chem. Soc. 2001, 123, 4609-4610.
(6) (a) Hicks, F. A.; Buchwald, S. L. J . Am. Chem. Soc. 1996, 118,
11688-11689. (b) Hicks, F. A.; Buchwald, S. L. J . Am. Chem. Soc. 1999,
121, 7026-7033. (c) Sturla, S. J .; Buchwald, S. L. J . Org. Chem. 1999,
64, 5547-5550.
(7) Shibata. T.; Takagi, K. J . Am. Chem. Soc. 2000, 122, 9852-9853.
(8) J eong, N.; Sung, B. K.; Choi, Y. K. J . Am. Chem. Soc. 2000, 122,
6771-6772.
We report here rhodium complex-catalyzed carbonyla-
tion using aldehydes as a CO source under an argon
atmosphere.15,16 A mechanistic study of CO transfer and
an enantioselective reaction with chiral Rh complex are
also described.
(9) (a) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe, I. Tetrahedron
Lett. 2000, 41, 891-895. (b) Hiroi, K.; Watanabe, T.; Kawagishi, R.;
Abe, I. Tetrahedron: Asymmetry 2000, 11, 797-808. (c) Sturla, S. J .;
Buchwald, S. L. J . Org. Chem. 2002, 67, 3398-3403.
(10) (a) Alyea, E. C.; Meek, D. W. In Catalytic Aspects of Metal
Phosphine Complexes; American Chemical Society: Washington, D.C.,
1980; Chapter 4, pp 65-83. (b) Doughty, D. H.; Pignolet, L. H. In
Homogeneous Catalysis with Metal Phosphine Complexes; Pignolet, L.
H., Ed.; Plenum: New York, 1983; Chapter 11, pp 343-375. (c) J ardine,
F. H. In Carbonylations; Colquhoun, H. M., Thompson, D. J ., Twigg,
M. V., Eds.; Plenum: New York, 1991; Chapter 11, pp 407-469.
(11) (a) Ohno, K.; Tsuji, J . J . Am. Chem. Soc. 1968, 90, 99-107. (b)
Blum, J .; Oppenheimer, E.; Bergmann, E. D. J . Am. Chem. Soc. 1967,
89, 2338-2341.
(12) Beck, C. M.; Rathmill, S. E.; Park, Y. J .; Chen, J .; Crabtree, R.
H.; Liable-Sands, L. M.; Rheingold, A. L. Organometallics 1999, 18,
5311-5317.
(13) Shimizu, Y.; Mitsuhashi, H.; Capri, E. Tetrahedron Lett. 1966,
4113-4114.
(14) Decarbonylated CO from formic acid is utilized in metal-
catalyzed hydroxycarbonylation: Simonato, J .-P.; Walter, T.; Me´tivier,
P. J . Mol. Catal. A 2001, 171, 91-94 and references therein.
(15) For a preliminary communication of this work, see: Shibata,
T.; Toshida, N.; Takagi, K. Org. Lett. 2002, 4, 1619-1621.
10.1021/jo0262661 CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/20/2002
7446
J . Org. Chem. 2002, 67, 7446-7450

Rhodium Complex-Catalyzed Pauson-Khand-Type Reaction
TABLE 2. Ca r bon yla tive Cou p lin g of 1a w ith Va r iou s
CO Sou r cesa
entry
CO source (equiv)
time, h
yield, %
1
2
3
cinnamaldehyde (20)
cinnamaldehyde (5)
cinnamaldehyde (1.2)
cinnamaldehyde (1.2)
cinnamaldehyde (20)
benzaldehyde (20)
benzaldehyde (1.2)
benzaldehyde (20)
2-hexenal (20)
2
3
3
3
24
3
4
24
2
2
24
5
98
93
83
80
54
87
12
18
68
30
31
85
F IGUR E 1. Carbonylative coupling with CO generated by
decarbonylation.
4b
5c
6
TABLE 1. Scr een in g of Va r iou s Rh Com p lexes
7
8c
9
10
11
12d
hexanal (20)
CO gas
CO gas
entry
catalysta
time, h
yield, %
a
The reaction was carried out by using the 0.3 mmol scale and
2a was purified by preparative TLC, except entry 4. The reaction
b
1
2
3
4
5
6
1/2 [RhCl(CO)2]2
1/2 trans-[RhCl(CO)dppp]2
1/2 [Rh(cod)Cl]2+dppp
Rh(dppe)2Cl
Rh(dppp)2Cl
Rh(dppb)2Cl
4
4
6
12
2
20
13
67
75
37
98
43
was carried out by using the 2.1 mmol scale and 2a was purified
by bulb-to-bulb distillation. c The reaction was carried out at 60°C.
d
Xylene was used as solvent.
are necessary for a high yield and the use of almost an
equivalent amount of aldehyde and a lower reaction
temperature gave poor results (entries 6-8). When
2-hexenal was compared with hexanal, R,â-unsaturated
aldehyde was the better CO donor (entries 9 and 10).
These results imply that cinnamaldehyde is the best CO
source among these four aldehydes, and that a phenyl
group and carbon-carbon double bond are important
components of the CO donor. On the basis of the results
of decarbonylation in an NMR tube with Rh(dppp)2Cl (5
mol %) at 120 °C for 24 h in toluene-d8, cinnamaldehyde
is mostly consumed to give styrene, but only about 5%
of benzaldehyde is consumed.
a
dppp ) 1,3-bis(diphenylphosphino)propane, dppe ) 1,2-bis-
(diphenylphosphino)ethane, dppb ) 1,4-bis(diphenylphosphino)-
butane.
Resu lts a n d Discu ssion
We first examined intramolecular alkene-alkyne cou-
pling using [Rh(CO)2Cl]2 in the presence of cinnamal-
5a
dehyde as a CO source without a solvent at 120 °C under
an atmospheric pressure of argon. Enyne 1a was con-
sumed to give a complex mixture, but cyclopentenone 2a
was obtained in poor yield (Table 1, entry 1). This result
implies that the carbonyl moiety of aldehyde is incorpo-
rated into cyclopentenone, as expected. Under the same
reaction conditions, a carbonyl complex with a dppp
ligand5b gave a much better result (entry 2). Entry 3
shows that dppp complex prepared in situ without CO
ligand also has high catalytic activity. Among the isolated
rhodium complexes with bidentate phosphine ligands,
dppp was the best choice to give the product in very high
yield (entries 4-6).
We next examined the effect of aldehydes and the
amount of aldehyde as a CO source using Rh(dppp)2Cl
as a catalyst (Table 2). When cinnamaldehyde was used,
5 equiv of aldehyde was sufficient for high yield (entry
2). Even with almost an equivalent amount of the CO
source, the reaction proceeded smoothly to give 2a in good
yield (entry 3). Carbonylative coupling at a larger scale
proceeded within the same reaction time and simple
distillation gave the pure product 2a in almost the same
yield (entry 4). This means that all of these procedures
can be performed in a completely solvent-free system. It
is noteworthy that this reaction, which includes both
catalytic decarbonylation and Pauson-Khand-type cou-
pling, proceeds with a moderate yield at as low as 60 °C
(entry 5). In the case of benzaldehyde, excess amounts
When the present reaction was examined under an
atmospheric pressure of CO without solvent, a much
longer reaction time was needed and enone 2a was
obtained in low yield from a complex mixture (entry 11).
Even under typical reaction conditions for a Pauson-
Khand-type reaction (under an atmospheric pressure of
CO in xylene), the results (reaction time and yield) were
inferior to those with cinnamaldehyde as a CO source
(entry 12). These results show the advantage of a solvent-
free Pauson-Khand-type reaction using cinnamaldehyde
as a CO source.
Various enynes were examined by using an excess
amount (20 equiv: method A) and almost an equivalent
amount (1.2 equiv: method B) of cinnamaldehyde as a
CO source in the presence of Rh(dppp)2Cl (Table 3).
Enynes 1b,c bridged by heteroatoms such as oxygen and
nitrogen gave good results with a short reaction time (2
h) to give the corresponding enones 2b,c (entries 1 and
2). The yield by method B is good, but is lower than that
by method A. Enyne 1d with an alkyl substituent on
alkyne was also an appropriate substrate for providing
2d in high yield (entry 3). The carbonylative coupling of
enynes 1e,f bridged by a carbon chain took a longer
reaction time than that of enynes bridged by hetero-
atoms, but enones 2e,f were obtained in acceptable yields
(entries 4 and 5) and methods A and B gave almost the
same results. Enyne 1g with a 1,1-disubstituted olefin
(16) Independently, Pauson-Khand-type reaction with pentafluo-
robenzaldehyde as a CO source in xylene was reported, see: Morimoto,
T.; Fuji, K.; Tsutsumi, K.; Kakiuchi, K. J . Am. Chem. Soc. 2002, 124,
3806-3807.
J . Org. Chem, Vol. 67, No. 21, 2002 7447

Shibata et al.
F IGURE 2. Proposed mechanism by direct CO transfer.
TABLE 3. Ca r bon yla tive Cou p lin g of Va r iou s En yn es
w ith Cin n a m a ld eh yd e a s a CO Sou r ce
TABLE 4. Ca r bon yla tive Cou p lin g u n d er Ar F low a n d
Ar Bu bblin g Con d ition s
entry
condition of Ar
flow rate, mL/min
yield, %
1
2
3
flow
flow
bubbling
150
750
150
63
66
64
a
Rh(dppp)2Cl:enyne:cinnamaldehyde ) 0.05:1.0:20. b Rh(dppp)2-
Cl:enyne:cinnamaldehyde ) 0.05:1.0:1.2.
F IGURE 3. Label experiment with use of 13CO.
is a rather inactive substrate in the Pauson-Khand-type
reaction, but coupling proceeded to give 2g in good yield
by both methods A and B.
4). We investigated different flow rates, but the results
were almost the same (entries 1 and 2). Even when argon
was bubbled into the reaction mixture, the yield was not
significantly changed (entry 3). If free CO exists in the
liquid phase or gas phase of the reaction vessel, different
flow rates of argon and bubbling of argon should signifi-
Figure 2 shows the reaction mechanism with 1a as a
representative enyne. The catalytic cycle on the left is
the established mechanism of decarbonylation from an
aldehyde10 and carbon monoxide is introduced into met-
allacyclopentene C. As a result, the carbonyl moiety of
aldehyde is incorporated into cyclopentenone.17 Moreover,
we propose a novel direct CO transfer from a decarbon-
ylative cycle to a Pauson-Khand-type reaction. Thus,
almost no free CO was generated and CO for carbonyla-
tive coupling was mainly provided by metal carbonyl
complex A, rather than by free CO. The following results
(Table 4 and Figure 3) support this hypothesis.
(17) A reaction mechanism with one catalytic cycle is also possible,
where metal carbonyl complex A itself acts as a catalyst for carbon-
ylative coupling. But this mechanism conflicts with highly enantiose-
lective induction by chiral diphosphine (Table 6), since the dissociation
of phosphine ligand from the metal center is needed for coordination
of an enyne, which is an enantiomerically differentiated step.
Carbonylative coupling with cinnamaldehyde as a CO
source was examined under argon flow conditions (Table
7448 J . Org. Chem., Vol. 67, No. 21, 2002

Rhodium Complex-Catalyzed Pauson-Khand-Type Reaction
TABLE 5. Ad va n ta ge of En a n tioselective Cou p lin g w ith
Ald eh yd e u n d er Solven t-F r ee Con d ition s
TABLE 6. En a n tioselective Cou p lin g of Va r iou s En yn es
w ith Cin n a m a ld eh yd e a s a CO Sou r cea
entry
CO source
cinnamaldehyde none
CO gas none
cinnamaldehyde xylene
CO gas xylene
solvent time, h yield, % ee, %
1
4
4
89
23
54
51
82
60
8
2a
3
36
36
4
10
a
Chiral catalyst was prepared in xylene and enyne 1a was
added after removing xylene.
cantly affect carbonylative coupling. Therefore, these
results imply that free CO is not generated in this
reaction.
Next, carbonylative coupling was performed in the
presence of cinnamaldehyde (1.2 equiv) under a partial
pressure of 13CO (Figure 3).5c Only 10% of the resulting
cyclopentenone contained 13CO. A control experiment
showed that carbonylative coupling proceeded with CO
gas as a CO source without aldehyde. A calculation based
on the amount of recovered cinnamaldehyde (0.44 equiv)
indicates that most of the consumed aldehyde (93%) was
incorporated into cyclopentenone even under a CO at-
mosphere. These results also suggest that the carbonyl
moiety of cyclopentenone is mainly supplied by the metal
carbonyl complex rather than by free CO.
We further studied an enantioselective reaction using
cinnamaldehyde as a CO source (Table 5). A chiral
catalyst was prepared in situ from [Rh(cod)Cl]2 and
tolBINAP (2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl)
and was used in the carbonylative reaction under solvent-
free conditions.18 The coupling of enyne 1a proceeded
smoothly to give 2a in good yield and ee (Table 5, entry
1).19 When CO gas was used as a CO source under the
same reaction conditions, both yield and ee significantly
decreased (entry 2). When asymmetric carbonylative
coupling was examined in xylene, the yield was moderate
even with a longer reaction time but the ee was very poor
both in the presence of cinnamaldehyde and under an
atmospheric pressure of CO (entries 3 and 4). Rhodium
cationic complex, which is prepared in situ from [RhCl-
(CO)2]2, chiral phosphine, and AgOTf, has been reported
to be an efficient chiral catalyst.8 Therefore, these results
imply that the solvent-free conditions with aldehyde as
a CO source have an advantage for a high yield and ee
in enantioselective coupling catalyzed by a noncationic
Rh complex.
a
[Rh(cod)Cl]2:tolBINAP:enyne:cinnamaldehyde ) 0.05: 0.10:
1.0:20. The reaction was carried out at 120 °C. b Benzaldehyde was
used as a CO source in place of cinnamaldehyde.
ee than cinnamaldehyde only for allyl propargylamine
1c (entries 6 and 7). The enantioselective coupling of
allylpropargylmalonate 1e also proceeded in good yield
with moderate ee (entry 8).
Con clu sion s
We developed a rhodium complex-catalyzed Pauson-
Khand-type reaction based on a new experimental pro-
tocol. In place of CO gas, which is very poisonous and
must be handled with caution in an efficient fume hood,
aldehyde was used as a CO source for carbonylation. The
reaction proceeded efficiently even under solvent-free
conditions to give various bicyclic enones in high yield.
Argon flow and 13C-labeling experiments indicated that
almost no free CO exists in the reaction scheme and CO
generated by the decarbonylation of aldehyde is directly
incorporated into carbonylative coupling. Moreover, highly
enantioselective coupling was also achieved by using
chiral and noncationic Rh complex under solvent-free
conditions.
Under the optimal reaction conditions, other allyl
propargyl ethers were also transformed into chiral enones
in high ee (Table 6, entries 1-5). In particular, enyne 1i
gave the best result of 90% ee (entry 3). In the case of
enyne 1g, benzaldehyde gave a better yield than cinna-
maldehyde (entries 4 and 5). Although the reason for this
result is unclear, benzaldehyde gave a significantly better
Exp er im en ta l Section
Gen er a l. [RhCl(CO)2]2 and [Rh(cod)Cl]2 were obtained
commercially. trans-[RhCl(CO)dppp]220 and RhL2Cl (L ) dppe,
dppp, dppb) were prepared as reported in the literature.21
Aldehydes were distilled from CaCl2 prior to use.
(18) A recent example of solvent-free enantioselective reaction with
organometallic compounds: Sato, I.; Saito, T.; Soai, K. Chem. Commun.
2000, 2471-2472.
(19) From the sign of optical rotation, the absolute configuration of
obtained 2a proved to be S (ref 3b). This means that the mechanism
of asymmetric induction with aldehyde as
Rh-tolBINAP system is the same as that with CO gas (refs 7 and 8).
a CO source by the
(20) Sanger, A. R. J . Chem. Soc., Dalton Trans. 1977, 120-129.
J . Org. Chem, Vol. 67, No. 21, 2002 7449

Shibata et al.
Exp er im en ta l P r oced u r e for th e P a u son -Kh a n d -Typ e
Rea ction w ith Cin n a m a ld eh yd e u n d er Solven t-F r ee
Con d ition s (Ta ble 2, en tr y 4). Rh(dppp)2Cl (101 mg, 0.105
mmol), enyne 1a (362 mg, 2.10 mmol), and cinnamaldehyde
(333 mg, 2.52 mmol) were placed in a flask under an atmo-
sphere of argon and the mixture was stirred at 120 °C for 3 h.
The flask was then attached to a bulb-to-bulb distillation
apparatus. After removing styrene and a small amount of
recovered cinnamaldehyde, the pure product 2a was distilled
(334 mg, 1.67 mmol, 80% yield).
Gen er a l P r oced u r e for th e En a n tioselective P a u son -
Kh a n d -Typ e Rea ction w ith Cin n a m a ld eh yd e u n d er Sol-
ven t-F r ee Con d ition s (Ta ble 6). [Rh(cod)Cl]2 (8.1 mg, 0.016
mmol), (S)-tolBINAP (22.4 mg, 0.033 mmol), enyne 1 (0.33
mmol), and cinnamaldehyde (872 mg, 6.60 mmol) were placed
in a flask under an atmosphere of argon. The reaction mixture
was then stirred at 120 °C for the number of hours shown in
Table 6. After the exclusion of excess cinnamaldehyde, the
crude product was purified by thin-layer chromatography
(TLC) and pure bicyclic enone 2 was obtained. The ee was
determined by HPLC analysis using a 4 mm × 250 mm chiral
column (conditions: 254 nm UV detector, rt, flow rate of
eluent ) 1.0 mL/min).
2-P h en yl-7-oxa bicyclo[3.3.0]oct-1-en -3-on e (2a ). Spec-
tral data accorded with those in the literature.5c,22 [R]28 7.30
D
(c 1.25, CHCl3). Ee was determined to be 82% by HPLC
analysis, using Daicel Chiralpak AD (eluent ) 10% 2-propanol
in hexane; retention time ) 12 min for minor isomer and 17
min for major isomer).
Ack n ow led gm en t. This research was supported by
a Grant-in-Aid for Scientific Research on Priority Areas
(A) “Exploitation of Multi-Element Cyclic Molecules”
from the Ministry of Education, Culture, Sports, Science
and Technology, J apan. T.S. thanks the Nagase Foun-
dation for supporting this work. We thank the Center
for Instrumental Analysis, Kyushu Institute of Technol-
ogy for the measurement of analytical data.
Su p p or tin g In for m a tion Ava ila ble: Listing of spectral
data for new compounds and determination of ee by HPLC
for all compounds (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
J O0262661
(22) Berk, S. C.; Grossmann, R. B.; Buchwald, S. L. J . Am. Chem.
Soc. 1994, 116, 8593-8601.
(21) J ames, B. R.; Mahajan, D. Can. J . Chem. 1979, 54, 180-187.
7450 J . Org. Chem., Vol. 67, No. 21, 2002