Rhodium-catalyzed pauson-khand-type reaction using alcohol as a source of carbon monoxide

Article abstract of DOI:10.1002/anie.201001246

Three in one pot! Bicyclic cyclopentenones have been synthesized from enynes in alcohol in the presence of a rhodium catalyst through a newly developed auto-tandem catalytic reaction. This process combines three mechanistically distinctive reactions - an

Full text of DOI:10.1002/anie.201001246

Communications
DOI: 10.1002/anie.201001246
Pauson–Khand Reaction
Rhodium-Catalyzed Pauson–Khand-Type Reaction Using Alcohol as a
Source of Carbon Monoxide**
Ji Hoon Park, Yoonhee Cho, and Young Keun Chung*
The invention of increasingly rapid, efficient, and convenient
strategies to obtain valuable compounds from readily avail-
able starting materials is one of the primary objectives of
modern chemistry. To this end, chemists have long been
interested in tandem or cascade reactions, whereby one
catalyst promotes two or more distinct chemical transforma-
tions in a single flask without the need for intermediate
workup procedures or purification.[1] When considering these
sequential reactions, one often needs to consider the compat-
ibility of a catalyst with the residual material derived from the
proceeding steps.
Owing to the recent attention given to green chemistry,
gaseous carbon monoxide used in carbonylation reactions has
been replaced by organic and inorganic carbonyl com-
pounds.[2] In many cases, the substitute for carbon monoxide
was an aldehyde,[3] which is normally prepared from the
corresponding alcohol. We envisioned the use of alcohols as a
carbon monoxide source in the presence of a catalyst
(Scheme 1) and supposed that the ability to use the alcohol
itself would be highly beneficial.
generated metal carbonyl complex is used in a successive
carbonylation reaction, the catalytic system might be effec-
tive. To verify our assumption, we explored rhodium com-
plexes, which are known catalysts for the transformation of
alcohols into aldehydes,[5] for the decarbonylation of alde-
hyde[6] and for the Pauson–Khand reaction.[7] Normally, three
kinds of rhodium compounds might be needed to catalyze
these three conceptually different reactions. However, we
wanted to develop a catalytic one-pot reaction using just one
rhodium compound as a catalyst. Herein we report our
preliminary results for the rhodium-catalyzed intramolecular
Pauson–Khand-type reaction using an alcohol as the source of
carbon monoxide.
Initially we studied an intramolecular Pauson–Khand-
type reaction using allyl propargyl tosylamide (1a) as a model
substrate using ethanol as a CO source (Table 1). As shown in
Table 1, we screened a variety of rhodium complexes that are
known as effective catalysts in decarbonylation of aldehydes
and Pauson–Khand-type reactions. To our delight, the
Pauson–Khand-type product 1b was obtained in reasonable
yields with the concomitant formation of the reductive
cyclization compound 1c.[8] Compound 1c was derived from
Table 1: Catalytic Pauson–Khand-type reaction of 1a with ethanol.[a]
Scheme 1. Hypothesis of the cascade reaction.
Entry
Catalyst
mol% T [8C]
1b [%][b]
1c [%][b]
Because of the unfavorable thermodynamic nature of the
dehydrogenation reaction of alcohols to yield the correspond-
ing aldehydes, the yield of aldehyde and hydrogen in a closed
system is low. However, if the aldehyde produced from the
alcohol is continually removed from the system through a
decarbonylation reaction as a second process,[4] and the thus
1
2
3
4
5
6
7
[{Rh(CO)Cl(dppp)}2]
[{Rh(CO)Cl(dppp)}2]
[{Rh(CO)Cl(dppp)}2]
[Rh(CO)Cl(dppe)]
[{Rh(CO)Cl(dppb)}2]
[Rh(dppp)2Cl]
8
8
8
16
8
16
120
70
40
70
70
70
70
61
66
36
33
22
trace
16
31(45)[c]
trace
18(65)[c]
24(32)[c]
n.r.
34
[{Rh(cod)Cl}2]
/binap
8
(16)[d]
8
[{Rh(cod)Cl}2]
/dppp
[RhCl(PPh3)3]
[{Rh(CO)Cl(dppp)}2]
[{Rh(CO)Cl(dppp)}2]
[{Rh(CO)Cl(dppp)}2]
8
70
48
49
[*] J. H. Park, Y. Cho, Prof. Dr. Y. K. Chung
Intelligent Textile System Research Center
and Department of Chemistry
(16)[d]
9
16
8
4
70
70
70
70
n.r.
n.r.
58
10[e]
11
12
College of Natural Sciences, Seoul National University
Seoul 151-747 (Korea)
Fax: (+82)2-889-0310
37
53
2
41
E-mail: ykchung@snu.ac.kr
[a] Reaction conditions: 1a (0.15 mmol), ethanol (10 equiv), toluene
(2 mL), and 18 h. [b] Yield of isolated product. [c] The numbers in
parenthesis represent the amount of recovered starting materials.
[d] Amount of phosphine used. [e] 5 mol% of NaOH was added. cod=
[**] This research was supported by the Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Sience and Technology (2009-0093864
and R11-2005-065). Y.H.C. thanks the Brain Korea 21 fellowships.
cycloocta-l,5-diene,
dppb=butane-l,4-diylbis(diphenylphosphane),
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201001246.
dppe=ethane-l,2-diylbis(diphenylphosphane), dppp=propane-l,3-diyl-
bis(diphenylphosphane), Ts=4-toluenesulfonyl, n.r.=no reaction.
5138
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Angew. Chem. Int. Ed. 2010, 49, 5138 –5141

Angewandte
Chemie
the reaction of 1a with the generated hydrogen or rhodium
hydride intermediate.[9] The yield of 1b was highly sensitive to
the rhodium complexes that were used. The best yield (66%;
Table 1, entry 2) was observed with [{Rh(CO)Cl(dppp)}2] at
708C. Indeed, the reaction could even be conducted at much
lower temperature (408C; Table 1, entry 3).[10] The formation
of 1b was observed with [{Rh(CO)Cl(dppb)}2] (18% yield;
Table 1, entry 5) and [Rh(dppp)2Cl] (24% yield; Table 1,
entry 6). Strangely, complexes [Rh(CO)Cl(dppe)] and [{Rh-
(cod)Cl}2] with binap were inactive (Table 1, entries 4 and 7).
As expected, no reaction was observed with a monophos-
phine rhodium complex (Table 1, entry 9).[6b] Remarkably,
[{Rh(CO)Cl(dppp)}2] uniquely showed its effectiveness in the
oxidation of ethanol to acetaldehyde, in the decarbonylation
of acetaldehyde to carbon monoxide and methane, and in the
Pauson–Khand-type reaction. To enhance the oxidative
dehydrogenation of ethanol, a base such as NaOH was
added, but turned out to be detrimental and no reaction
occurred (Table 1, entry 10).[4a] When the amount of
[{Rh(CO)Cl(dppp)}2] used was lowered to 4 mol% and
2 mol% (Table 1, entries 11 and 12), the catalytic system
was still quite effective and the corresponding product 1b was
isolated in 58% and 41% yield, respectively.
(Table 2, entry 6). Olefinic alcohols such as allyl alcohol and
cinnamyl alcohol also gave high yields of the product (Table 2,
entries 7–11). For unsaturated alcohols, it was expected that
the yield of a reductive cyclization product should be
decreased.[11] The best yield (95%; Table 2, entry 9) was
observed when 10 equivalents of cinnamyl alcohol were used
in 2.0 mL of xylene at 1308C for 18 hours.[12] When the
amount of cinnamyl alcohol used was lowered to 1.2 equiv-
alents with 4 mol% of the catalyst, the yield was still 91%
after 2 hours of reaction time (Table 2, entries 7–11). An aryl
group and a carbon–carbon double bond are important
characteristics of a good CO donor.[13] Moreover, better
yields were observed at 1308C than at 708C, presumably as a
result of the enhancement of both the decarbonylation
reaction and the subsequent carbonylative cycloaddition at
high temperature.
As an alternative source of carbon monoxide, carbohy-
drates such as glucose[14] and xylitol were also exploited. In
principle, they can donate six or five carbon monoxide groups,
but they are almost insoluble in organic solvents. However,
when 0.2 equivalents of glucose and 0.3 equivalents of xylitol
were used as a CO source, 52% and 43% of the correspond-
ing products were isolated with a concomitant formation of an
enyne-dimerized product (Scheme 2).[15]
To lower the amount of 1c formed, we screened a variety
of hydrogen acceptors including methyl methacrylate, 2-
cyclohexenone, diphenylacetylene, and styrene. However,
they were ineffective and sometimes no reaction was
observed.
By using [{Rh(CO)Cl(dppp)}2] as a catalyst in the intra-
molecular Pauson–Khand-type reaction of 1a, we screened
diverse alcohols that could be easily dehydrogenated and
decarbonylated to give a high yield of cyclopentenone.
Primary mono alcohols such as n-propanol, n-pentanol, and
n-octanol gave reasonable to high yields (61–81%; Table 2,
entries 2–4) of the product. On the other hand, methanol gave
a lower yield (22%; Table 2, entry 1), presumably because of
its low boiling point. Ethylene glycol was quite efficient
Scheme 2. Using carbohydrates as multiple CO sources. Reaction
conditions: in 2 mL of diglyme at 1608C (glucose); in 2 mL of toluene
at 1108C (xylitol).
We next screened various enyne substrates for the intra-
moleular Pauson–Khand-type reaction under optimized reac-
tion conditions. As shown in Table 3, the catalytic system is
quite effective for giving high yields (53–99%) of the
intramolecular Pauson–Khand-type products. In the cases of
Table 3, entries 1, 3, and 6, a considerable amount (12–24%
yields) of a reductive cyclization was observed. For entries 7
and 8, an intricate mixture of byproducts was formed. The
highest yield (99%) was obtained for the substrate that could
be hardly reductively cyclized under the given reaction
conditions (Table 3, entry 2).[16] Also, a 1,7-enyne compound
was transformed into bicyclo[4.3.0]nonenone in high yield
(74%; Table 3, entry 8).
We then conducted a preliminary mechanistic investiga-
tion. When a Pauson–Khand reaction was carried out in the
presence of ethanol, we could confirm the formation of
methane by GC (see the Supporting Information) in addition
to the Pauson–Khand product and a reductive cyclization
product. As we expected, hydrogen is transferred from the
alcohol to the enyne, and the aldehyde formed is decarbony-
lated to afford methane by the rhodium catalyst. The evolved
Table 2: Pauson–Khand-type reaction of 1a with various alcohols
catalyzed by [{Rh(CO)Cl(dppp)}2].[a]
Entry Alcohol (equiv)
Cat. [mol%] T [8C] t [h] Yield [%][b]
1
2
3
4
5
6
7
8
methanol (10)
n-propanol (10)
n-pentanol (10)
n-octanol (10)
8
8
8
8
8
8
8
8
8
4
4
4
70
70
18
18
18
18
18
18
18
18
18
18
2
22(26)[c]
63(37)[c]
73(25)[c]
62(36)[c]
81(12)[c]
69(29)[c]
60(32)[c]
67(18)[c]
95
130
70
130
130
70
130
130
130
130
130
n-octanol (10)
ethylene glycol (5)
allyl alcohol (10)
allyl alcohol (10)
cinnamyl alcohol (10)
cinnamyl alcohol (10)
cinnamyl alcohol (4)
phenethyl alcohol (4)
9
10[d]
11[e]
12[d]
90
91(4)[c]
69(24)[c]
2
[a] Reaction conditions: 1a (0.15 mmol), alcohol, toluene (2 mL, 708C)
or xylene (2 mL, 1308C). [b] Yield of isolated product. [c] The numbers in
parenthesis represent the yield of reductive cyclized product. [d] The
reaction was conducted without solvent. [e] The reaction was carried out
in xylene (0.5 mL).
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Communications
Table 3: Scope of the rhodium-catalyzed Pauson–Khand-type reaction
with cinnamyl alcohol.
method that uses alcohols as a CO source in the presence of
the catalyst [{Rh(CO)Cl(dppp)}2]. Any primary alcohol can
be directly used as a CO source. The carbonylation method
developed in this study is more reliable and accessible than
other currently available methods and should promote
further advances in this area. More detailed studies are
required to fully understand the mechanism of these sequen-
tial reactions.
Entry Product
Reaction conditions t [h] Yield [%][c]
1
2b
3b
4b
5b
A
B
B
A
2
2
2
4
57(21)
99
Experimental Section
Preparation of 1b using ethanol in toluene: [{Rh(CO)Cl(dppp)}2]
(7.0 mg, 6 mmol) and toluene (1 mL) were added to a flame-dried
Schlenk tube equipped with a stirring bar. The mixture was stirred at
RT for 5 min before enyne 1a (0.15 mmol, 48 mg) in toluene (1 mL)
and ethanol (10 equiv, 1.5 mmol) were added. After the reaction
mixture had been stirred for 18 h at 708C the mixture was purified by
flash chromatography on silica gel (eluent: n-hexane/EtOAc 5:2 v/v)
to afford 1b as a white solid.
2
3[d]
68(24)
90
4[d]
Preparation of 1b using cinnamyl alcohol without solvent:
[{Rh(CO)Cl(dppp)}2] (7.0 mg, 6 mmol), enyne 1a (0.15 mmol,
48 mg), and cinnamyl alcohol (0.6 mmol, 80 mg) were added to a
flame-dried Schlenk tube equipped with a stirring bar. After the
reaction mixture had been stirred for 2 h at 1308C, the reaction
mixture was purified by flash chromatography on silica gel (eluent: n-
hexane/EtOAc 5:2 v/v) to afford 1b as a white solid.
5
6
7
8
6b
7b
8b
9b
B
A
A
B
12
18
2
93
77(12)
53
Received: March 2, 2010
Revised: April 29, 2010
Published online: June 16, 2010
4
74
Keywords: alcohols · carbonylation · dehydrogenation ·
.
rhodium · tandem reactions
[a] Reaction conditions A: enyne (a, 0.15 mmol), cinnamyl alcohol
(1.2 equiv), xylene (0.5 mL). [b] Reaction conditions B: enyne
(0.15 mmol), cinnamyl alcohol (4 equiv), no solvent. [c] Yield of isolated
product. [d] 0.3 mmol of enyne was used. Bn=benzyl.
[1] a) A. Ajamian, J. L. Gleason, Angew. Chem. 2004, 116, 3842;
Angew. Chem. Int. Ed. 2004, 43, 3754; b) C. J. Chapman, C. G.
Frost, Synthesis 2007, 1; c) D. E. Fogg, E. N. dos Santos, Coord.
Chem. Rev. 2004, 248, 2365; d) P. A. Evans, J. E. Robinson, J.
Am. Chem. Soc., 2001, 123, 4609.
[2] a) T. Morimoto, K. Kakiuchi, Angew. Chem. 2004, 116, 5698;
Angew. Chem. Int. Ed. 2004, 43, 5580; b) T. Morimoto, M.
Fujioka, K. Fuji, K. Tsutsumi, K. Kakiuchi, Pure Appl. Chem.
2008, 80, 1079.
[3] a) T. Morimoto, K. Fuji, K. Tsutsumi, K. Kakiuchi, J. Am. Chem.
Soc. 2002, 124, 3806; b) T. Shibata, N. Toshida, K. Takagi, J. Org.
Chem. 2002, 67, 7446; c) H. W. Lee, L. N. Lee, A. S. C. Chan,
F. Y. Kwong, Eur. J. Org. Chem. 2008, 3403.
[4] A decarbonylation of alkanals has already been proposed to
promote the dehydrogenation of alcohols, see: a) D. Morton,
D. J. Cole-Hamilton, I. D. Utuk, M. Paneque-Sosa, M. Lopez-
Poveda, J. Chem. Soc., Dalton Trans. 1989, 489; b) D. Morton,
D. J. Cole-Hamilton, J. Chem. Soc., Chem. Commun. 1987, 248.
[5] a) H. Alper, K. Hachem, S. Gambarotta, Can. J. Chem. 1980, 58,
1599; b) E. Delgado-Lieta, M. Luke, R. F. Jones, D. J. Cole-
Hamilton, Polyhedron 1987, 1, 839.
CO reacts with the enyne in the presence of the rhodium
catalyst.
To follow high-temperature reactions, a high-temperature
NMR experiment was performed (see the Supporting Infor-
mation). Enyne 1a was heated with cinnamyl alcohol in the
presence of a catalytic amount of [{Rh(CO)Cl(dppp)}2] in
[D8]toluene at 1308C. From the beginning, the signal corre-
sponding to the aldehyde was observed. The signals corre-
sponding to the Pauson–Khand-type reaction product were
also observed in the early stage of heating. Thus, the
observations suggested that the dehydrogenation of cinnamyl
alcohol and the decarbonylation of cinnamaldehyde occur
almost at the same time. As the processes are not sequential,
the precise mechanism by which a catalyst influences the
three processes is difficult to elucidate. Based on the above
observation and on other previous studies,[6e] a plausible
mechanism for the rhodium-catalyzed tandem transformation
is proposed (see the Supporting Information).
[6] a) G. Wilkinson, C. J. Nyman, M. C. Baird, J. Chem. Soc. A 1968,
348; b) D. H. Doughty, L. H. Pignolet, J. Am. Chem. Soc. 1978,
100, 7083; c) M. Kreis, A. Palmelund, L. Bunch, R. Madsen, Adv.
Synth. Catal. 2006, 348, 2148; d) T. C. Fessard, S. P. Andrews, H.
Motoyoshi, E. M. Carreira, Angew. Chem. 2007, 119, 9492;
Angew. Chem. Int. Ed. 2007, 46, 9331; e) P. Fristrup, M. Kreis, A.
Palmelund, P. Norrby, R. Madsen, J. Am. Chem. Soc. 2008, 130,
5206; f) M. A. Garralda, Dalton Trans. 2009, 3635.
In conclusion, we have developed a new version of an
auto-tandem catalytic intramolecular Pauson–Khand-type
reaction in a one-pot reaction procedure, which is an
inexpensive, safe, and environmentally benign carbonylation
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[7] a) N. Jeong in Modern Rhodium-Catalyzed Organic Reactions
(Ed.: P. A. Evans), Wiley-VCH, Weinheim, 2005, pp. 215 – 240;
b) T. Shibata, Adv. Synth. Catal. 2006, 348, 2328; c) J. Pꢀrez-
Castells, Top. Organomet. Chem. 2006, 19, 207; d) H. Wang, J. R.
Sawyer, P. A. Evans, M.-H. Baik, Angew. Chem. 2008, 120, 348;
Angew. Chem. Int. Ed. 2008, 47, 342.
[8] H. Y. Jang, M. J. Krische, Acc. Chem. Res. 2004, 37, 653.
[9] J. H. Park, Y. K. Chung, unpublished results.
[10] When the same reaction was carried out under bubbling N2, a
trace amount of 1c was formed but formation of 1b was not
observed.
[12] Formation of ethylbenzene (ca. 5%) was observed by GC–MS
analysis.
[13] T. Shibata, N. Toshida, K. Takagi, Org. Lett. 2002, 4, 1619.
[14] The major form of glucose is pyranose ring (98.6%) in aqueous
solution at 828C, see: a) R. N. Monrad, R. Madsen, J. Org.
Chem. 2007, 72, 9782; b) R. R. Maple, A. Allerhand, J. Am.
Chem. Soc. 1987, 109, 3168.
[15] According to the mass spectrometric investigation, the molec-
ular weight of the product was twice that of 1a, but its NMR
spectrum was too complicated to assign. Thus, we temporary call
the product an enyne-dimerized product.
[11] For unsaturated alcohols, an aldehyde species could be gener-
ated without the generation of hydrogen or a metal hydride
species through an allylic isomerization through coordination of
[16] When the same substrate was reacted in ethanol under the
optimized reaction conditions, the yield of the Pauson–Khand-
type product decreased to 43% and an alkyne hydrogenated
product instead of a reductive cyclized product was obtained in
35% yield.
À
the p C C bond followed by hydrogenation, see: A. Emery,
A. C. Oehlschlager, A. M. Unrau, Tetrahedron Lett. 1970, 11,
4401.
Angew. Chem. Int. Ed. 2010, 49, 5138 –5141
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