Catalytic tricarbonylation of alkynes with palladium catalysts

Article abstract of DOI:10.1246/cl.2005.1060

A novel catalytic process of introducing three CO units into alkynes by palladium-catalyzed alkoxycarbonylation was developed. Based on the fundamental studies on the behavior of organopalladium complexes, mechanisms to account for the mono- and tricarbon

Full text of DOI:10.1246/cl.2005.1060

1060
Chemistry Letters Vol.34, No.7 (2005)
Catalytic Tricarbonylation of Alkynes with Palladium Catalysts
Yusuke Izawa,y Isao Shimizu,ꢀy and Akio Yamamotoꢀyy
yDepartment of Applied Chemistry, School of Science and Engineering, Waseda University,
3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555
yyAdvanced Research Institute for Science and Engineering, Waseda University,
3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555
(Received April 21, 2005; CL-050548)
A novel catalytic process of introducing three CO units into
of DMF relative to methanol or by carrying out the reaction in
methanol, the amounts of the dicarbonylation products 4 and 5
were increased.
alkynes by palladium-catalyzed alkoxycarbonylation was devel-
oped. Based on the fundamental studies on the behavior of
organopalladium complexes, mechanisms to account for the
mono- and tricarbonylation processes are proposed.
PPh (0.2 equiv.)
3
Pd(OAc) (0.1 equiv.)
2
CO/O2
R CC H
1
+ MeOH
+
Solvent, 60 °C, 24 h
NaI (0.5 equiv.)
(15/5 atm)
(R = p-tolyl)
Catalytic carbonylation of alkynes provides convenient
routes to various unsaturated carboxylates that can be utilized
for synthesis of a variety of important organic compounds.1 Al-
kynes can be oxidatively carbonylated into alkynecarboxylates
with retention of the CꢁC bond or hydrocarbonylated into alke-
necarboxylates having the C=C bond in the presence of palla-
dium catalysts under carbon monoxide. However, mechanisms
of these carbonylation processes have not been satisfactorily
clarified and conditions to selectively produce mono- and/or
di-carbonylation products have not been well established.2
In the previous paper we have shown that a clean palladium-
catalyzed monocarbonylation proceeded under atmospheric
pressure of CO and oxygen without adding any other oxidant,
such as Cu(II) compound (Chart 1).3
(MeO2C)RC C(CO2Me)2
2
(MeO2C)RC CH(CO2Me)
4
MeO
MeO
MeO
O
O
O
5
O
RC CCO2Me
MeO
R
CO2Me
H
R
6
3
Chart 2.
Table 1. Oxidative carbonylation of 4-ethynyltoluene in vari-
ous solvents
Product Yielda/%
Run
Solvent
2
3
4
5
6
1
2
3
4
5
MeOH (2 mL)/THF (10 mL) trace
MeOH (2 mL)/DMF (10 mL) 18b
66
PPh3 (0.2 mol.amt.)
Pd(OAc)2 (0.1 mol.amt.)
9
MeOH (5 mL)/DMF (5 mL)
MeOH (8 mL)/DMF (2 mL)
MeOH
35b 36
11 10
13 19 37 16
R C
C
CO2Me
+
+
R C
C
H
CO/O2 MeOH
(1 atm)
DMF, rt, 72 h
4
trace 59
Chart 1.
aDetermined by H NMR. Isolated yield.
1
b
A mechanism proceeding through an intermediate palla-
dium complex having a methoxycarbonyl ligand coupled with
an alkynyl ligand was proposed to account for the oxidative
carbonylation of alkynes to produce alkyl alkynoates based on
properties of the isolated methoxycarbonyl- and alkynylpalla-
dium complexes.
Decrease in the CO pressure caused increase in the mono-
carbonylation product 6 at the cost of tricarbonylation product.
The tricarbonylation did not proceed at room temperature and
the starting alkyne was recovered unreacted. In the absence of
the iodide salt, only monocarbonylation product 6 was produced.
The use of NaBr or NaCl instead of the iodide gave no tricarbo-
nylation product. Aliphatic alkynes such as 1-heptyne gave the
tricarbonylation products as well as aromatic alkynes without
giving any mono- or dicarbonylation products, when the reac-
tions were carried out in the mixture containing methanol and
DMF in a comparable ratio under the pressure of CO (15 atm)
and O2 (5 atm).
Scheme 1 shows the mechanisms proposed to account for
the monocarbonylation as well as tricarbonylation proceeding
through a common methoxycarbonylpalladium intermediate
(B). Our previous work3 established the course of oxidation of
a Pd(0) complex E with molecular oxygen to a Pd(II) complex
A that is subsequently converted into the methoxycarbonylpalla-
dium species B upon reaction with CO and methanol with a base.
We have further confirmed that an isolated methoxycarbonyl-
Further examination of the reaction conditions on the oxida-
tive carbonylation process under the pressure of CO and oxygen
revealed that the oxidative tricarbonylation as well as dicarbon-
ylation took place when the reaction was performed under cer-
tain conditions in the presence of iodide, such as NaI and NEt4I
(Chart 2). Table 1 shows that the catalytic carbonylation of 4-
ethynyltoluene (p-tolylacetylene) depends strongly on the nature
of the solvent employed. When 4-ethynyltoluene was treated
with the mixture of methanol and THF under the pressure of
15 atm of CO and 5 atm of O2, the monocarbonylation product
6 was obtained predominantly, whereas the use of DMF in high-
er proportions in combination with methanol afforded tricarbon-
ylation products 2 and 3 (Runs 2 and 3 in Table 1) without
producing the monocarbonylation product under otherwise
similar conditions. However, upon reduction of the proportion
Copyright ꢀ 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.7 (2005)
1061
palladium complex B reacted with an alkyne in the presence of a
base to release methyl alkynecarboxylate, probably through an
intermediate C that produces the methyl alkynoate by reductive
elimination of the methoxycarbonyl and the alkynyl ligands.
dicarbonylation of alkynes under atmospheric pressure of CO.4
Effectiveness of the iodide in the catalytic tricarbonylation
process and the delicate influence of the compositions of the
solvent mixtures in performing the carbonylation process may
be associated with the dissociation of X from the palladium cen-
ter. Further detailed examination of the effect of the solvent
nature on the carbonylation process is required to maximize
the yield of the tricarbonylation products.
R
C C CO2Me
Pd0Ln
Oxidant, X-
(E)
(L = PPh3)
R
CO Me
2
A typical catalytic carbonylation of 4-ethynyltoluene under
the pressure of CO (15 atm) and O2 (5 atm) was performed
in a 100 mL stainless autoclave containing 4-ethynyltoluene
(131 mL, 1.00 mmol), Pd(OAc)2 (22.5 mg, 0.100 mmol), PPh3
(52.4 mg, 0.200 mmol), and NEt4I (129 mg, 0.502 mmol) dis-
solved in DMF (5 mL) and MeOH (5 mL). The autoclave was
immersed in an oil bath heated at 60 ꢂC for 24 h. The reaction
mixture was separated by passing through a celite column and
the organic layer was collected after washing with water fol-
lowed by drying with MgSO4. The tricarbonylation products
were collected by separation with column chromatography over
silica gel by eluting with a hexane/ethyl acetate mixture (1:10
ratio).
C
C
MeO
C
CO Me
2
2
(2)
O
C
R
CO2Me
CO2Me
OMe
LnPd
PdIIX2Ln
(A)
LnPd
C
CO2Me
C
(C)
(D)
R
(X = Anionic Ligand)
Path a
CO, MeOH
Base
R
C C CO2Me
(6)
.
O
C
HX Base
.
HX Base
OMe
R
C C H
LnPd
X
(B)
Use of aliphatic alkyne also gave the tricarbonylation prod-
ucts 2 and 3. Treatment of hept-1-yne under similar conditions
under the pressure of CO/O2 yielded the tricarbonylation prod-
uct 2 and 3 in 32% and 15%, respectively.
The di- and tricarbonylation products were identified with
spectroscopic methods (1H, 13C{1H} NMR, IR, and GC-MS)
and elemental analysis after purification by chromatography
(supplementary material attached).
Path b
CO
C
O
C
O
C
R
C
CO2Me
O
OMe
LnPd
MeO
C
OMe
MeOH, - HX
LnPd
R
CO2Me
X
(B)
OMe
MeO
O
Pd
Ln
O
O
O
- PdLn
C
C
C
C
MeO
MeO
R
CO2Me
R
CO2Me
(3)
References
1
a) B. Trost and I. Flemming, ‘‘Comprehensive Organic
Synthesis,’’ Pergamon, Oxford (1991). b) G. P. Chiusoli
and M. Costa in ‘‘Handbook of Organopalladium Chemistry
for Organic Synthesis,’’ ed. by E. Negishi, Wiley Inter-
science, New York (2002), Vol. II.
For recent reports, see: B. Gabriele, L. Veltri, G. Salerno, M.
Costa, and G. P. Chiusoli, Eur. J. Org. Chem., 2003, 1722,
and references cited therein.
Scheme 1. Proposed mechanism for the palldium-catalyzed
oxidative mono- and tricarbonylation of a terminal alkyne.
The tricarbonylation process found in the present study can
be accounted for by assuming insertion of the alkynecarboxy-
late, the monocarbonylation product 6, into the Pd-methoxycar-
bonyl bond in B (Path a) as shown in the center of Scheme 1.
The insertion of 6 coupled with another methoxycarbonylation
of B produces an intermediate D having the vinyl and the
methoxycarbonyl ligands. The reductive elimination of the vinyl
group substituted with the two methoxycarbonyl groups with
another methoxycarbonyl ligand in D produces the olefin 2
substituted with three methoxycarbonyl groups with regenera-
tion of the Pd(0) species E to carry the catalytic cycle.
Path b in Scheme 1 shows one of the possible routes for
production of the lactone 3 as the tricarbonylation product.
The process involves additional CO insertion into the vinyl-Pd
bond followed by cyclization and the transfer of the methoxy
groups. A similar palladium-catalyzed dicarbonylation of 1-al-
kynes to produce lactones has been observed in the catalytic
2
3
4
Y. Izawa, I. Shimizu, and A. Yamamoto, Bull. Chem. Soc.
Jpn., 77, 2033 (2004).
a) M. Gabriele, M. Costa, G. Salerno, and G. P. Chiusoli,
J. Chem. Soc., Perkin Trans. 1, 1994, 83. b) B. Gabriele,
G. Salerno, M. Costa, and G. P. Chiusoli, J. Organomet.
Chem., 503, 21 (1995). c) J. Tsuji, N. Iwamoto, and M.
Morikawa, J. Am. Chem. Soc., 86, 2095 (1964). d) A. V.
Malashkevich, L. G. Bruk, and O. N. Temkin, J. Phys. Chem.
A, 101, 9825 (1997). e) L. G. Bruk, I. V. Oshamina, A. P.
Kozlova, E. V. Borontsov, and O. N. Temkin, J. Mol. Catal.
A: Chem., 104, 9 (1995). f) Y. Sakurai, S. Sakaguchi, and
Y. Ishii, Tetrahedron Lett., 40, 1701 (1999).
Published on the web (Advance View) June 25, 2005; DOI 10.1246/cl.2005.1060