Hydrocarboxylation of unactivated internal alkynes with carboxylic acids catalyzed by dinuclear palladium complexes

Article abstract of DOI:10.1016/j.tetlet.2010.11.046

Dinuclear palladium complexes catalyzed addition reactions of carboxylic acid O-H bond to unactivated internal alkynes. The reaction afforded a trans-adduct selectively.

Full text of DOI:10.1016/j.tetlet.2010.11.046

Tetrahedron Letters 52 (2011) 248–250
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Hydrocarboxylation of unactivated internal alkynes with carboxylic acids
catalyzed by dinuclear palladium complexes
⇑
Naofumi Tsukada , Atsushi Takahashi, Yoshio Inoue
Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Dinuclear palladium complexes catalyzed addition reactions of carboxylic acid O–H bond to unactivated
internal alkynes. The reaction afforded a trans-adduct selectively.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 22 September 2010
Revised 27 October 2010
Accepted 4 November 2010
Available online 29 November 2010
Keywords:
Palladium
Catalysis
Carboxylic acid
Alkyne
Dinuclear transition metal complexes have been expected to
have novel and unique functions as catalysts in organic synthesis.1
The co-operation of two metal centers could enable various trans-
formations that are not possible using mononuclear metal com-
plexes. We have previously reported that dinuclear palladium
complexes with a novel bridging ligand, N,N0-bis[2-(diphenylphos-
phino)phenyl]amidinate2 (dpfam), served as catalysts for selective
addition reactions of various sp2 and sp C–H bonds to unactivated
alkynes,3 which were not possible using mononuclear palladium
complexes (Eq. 1). In the course of our study for the catalysis using
1, we found that the addition of carboxylic acid O–H bond to unac-
tivated internal alkynes proceeded in the presence of 1a (Eq. 2).
Hydrocarboxylation of alkynes with carboxylic acids is an atom
economical way to synthesize vinyl and alkenyl esters, some of
which are industrially important compounds.4 Although there
have been many reports concerning hydrocarboxylation catalyzed
by transition metals,4,5 intermolecular addition to internal alkynes
has been rather limited.6 Hidai and co-workers reported that a
cuboidal palladium–molybdenum cluster served as a catalyst for
addition to electron-deficient internal alkynes as well as terminal
alkynes.6a Unactivated internal alkynes react with several carbox-
ylic acids in the presence of silver salts.6b Ru3(CO)12 is also effective
for the hydrocarboxylation of unactivated alkynes to afford (Z)-
alkenyl esters.6c–e
N
N
N
N
Ph2P
PPh2
Ph2P
Pd
Me
Pd
Pd
X
P
Ph2
R
R
2
1a (X = OH, R = p-Tol)
1b (X = OH, R = Me)
1c (X = I, R = p-Tol)
1d (X = Br, R = p-Tol)
1e (X = Cl, R = p-Tol)
R'
H
1
+
R'
H
R
R
R
R
R
R
ð1Þ
ð2Þ
R' = aryl
alkenyl
alkynyl
R"C(=O)O
R
R
H
1
+
R"C(=O)O
H
Initially, the reaction of 3-hexyne with benzoic acid was carried
out under reaction conditions similar to that of the hydroaryla-
tion3a of internal alkynes using 1 (Eq. 3 and Table 1). Reactions
in the presence of 1 and tri-n-butylborane at 100 °C afforded Z-1-
ethylbut-1-enyl benzoate 37 as the sole product. No regio- and
stereoisomers were observed. Hydroxo-bridged complexes 1a
and 1b were more effective than halide-bridged complexes 1c–e.
Reaction using 1a or 1b as a catalyst afforded 3 in good yields
⇑
Corresponding author at present address: Department of Chemistry, Faculty of
Science, Shizuoka University, Shizuoka 422-8529, Japan. Tel./fax: +81 54 238 4759.
E-mail address: sntsuka@ipc.shizuoka.ac.jp (N. Tsukada).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.046

N. Tsukada et al. / Tetrahedron Letters 52 (2011) 248–250
249
Table 1
Table 2 summarizes the results of the reaction of 3-hexyne
with various carboxylic acids (Eq. 4). Most reactions with substi-
tuted benzoic acids also gave the corresponding alkenyl esters
4–12 (entries 1–9). While electron-donating groups slightly
decrease the yield of the products, electron-withdrawing groups
increase the yield (entries 1–4). An acetyl group at the ortho
position inhibits the reaction, probably due to deactivation of
the catalyst by chelation (entry 5). In several cases, small
amounts of isomers were observed by GC–MS. The structure of
the isomers was determined by 1H NMR spectra only in two reac-
tions where significant amounts of isomers were formed (entries
2 and 8). The standard reaction conditions are unsuitable for the
reaction with p-toluic acids (entry 9). In this case, the reaction
mixture was heterogeneous because only a small amount of
THF was used as the solvent and p-toluic acid has lower solubil-
ityandahighermeltingpoint. Althoughnitrogenousheteroaromatic
carboxylic acids such as 2-picolinic acid and pyrrole-2-carboxylic
acid inhibited the addition (entries 10 and 11), the reaction of
2-furoic acid or 2-thiophenecarboxylic acid gave the corresponding
adducts 15 and 16, respectively (entries 12 and 13). Alkenoic acids
can also be used for hydrocarboxylation (entries 14–16); the reac-
tion of cinnamic acid afforded the adduct 17 in a satisfactory yield.
Most aliphatic carboxylic acids exhibited low reactivity. Among
them, phenyl-substituted acids, such as phenylacetic acid and
hydrocinnamic acid were more reactive and adducts 24 and 25
were obtained from their reactions (entries 21 and 22).
Pd-catalyzed addition of benzoic acid to 3-hexynea
Run
Catalyst (mol %)
Additive
Yieldb (%)
1
2
3
4
5
6
7
8
9
1a (2)
1b (2)
1c (2)
1d (2)
1e (2)
1a (2)
B(n-Bu)3
B(n-Bu)3
B(n-Bu)3
B(n-Bu)3
B(n-Bu)3
None
71
65
27
44
41
53
55
51
4
1a (2)
1a (2)
2 (4)
Pd(PPh3)4 (4)
Pd(OAc)2 (4)
None
B(sec-Bu)3
LiAl(O-t-Bu)3H
B(n-Bu)3
B(n-Bu)3
B(n-Bu)3
B(n-Bu)3
10
11
12
0
0
0
a
A mixture of 3-hexyne (0.5 mmol) and benzoic acid (5.0 mmol) was stirred at
100 °C for 17 h in the presence of a palladium complex (0.01–0.02 mmol) and an
additive (0.15 mmol).
b
Determined by GC.
(entries 1 and 2). Although 1c–e were wholly ineffective in the pre-
vious hydroarylation,3a hydrocarboxylation proceeded in the pres-
ence of 1c–e to give 3 in moderate yields (entries 3–5). The
addition of tri-n-butylborane is not essential for hydrocarboxyla-
tion in contrast to hydroarylation; however, the absence of the
additive decreased the yield of 3 (entry 6). The addition of tri-
sec-butylborane or lithium tri-tert-butoxyaluminum hydride did
not affect the yield of 3 (entries 7 and 8). Next, several mononu-
clear complexes were employed as catalysts. The reaction did not
proceed in the presence of ordinary palladium catalysts such as
Pd(PPh3)4 and Pd(OAc)2 (entries 10 and 11). Only the mononuclear
complex 2, which has the same ligand as the dinuclear complexes
1 have, showed very low catalytic activity (entry 9).
2 mol% 1a
30 mol% BnBu3
O
+
Et
Et
R1 OH
100 ºC
17 h
ð4Þ
O
O
Et
H
R1
O
Et
4-25
catalyst
additive
100 ºC
17 h
O
Et
H
O
+
Et
Et
Ph
ð3Þ
Ph
OH
Et
Table 3 summarizes the results of the reaction of various
3
alkynes with benzoic acid (Eq. 5). Various dialkylethynes reacted
with benzoic acid as well as 3-hexyne to provide the corresponding
esters 26–29 (entries 1–4). Unfortunately, a hindered group inhib-
ited the reaction (entry 3) and the regioselectivity in the reaction of
2-octyne was low (entry 4). The regioselectivity increased slightly
in the reactions of phenyl-substituted alkynes (entries 6 and 7),
and was significantly improved in the reaction of methyl butyno-
ate, although the E/Z ratio was low (entry 9). Terminal alkynes such
as phenylacetylene and 1-hexyne afforded no adducts.
Table 2
Pd-catalyzed addition of various carboxylic acids to 3-hexynea
Run
R1
Product
Yieldb (%)
1
2
3
o-MeC6H4
o-MeOC6H4
o-CF3C6H4
o-FC6H4
4
5
6
58
40c
88
4
7
62
5
6
7
8
o-CH3(C@O)C6H4
m-MeC6H4
m-MeOC6H4
m-CF3C6H4
p-CH3C6H4
2-Pyrroryl
2-Pyridyl
8
9
Trace
24
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
41
32d
Trace
0
Table 3
9
Pd-catalyzed addition of benzoic acid to various alkynesa
10
11
12
13
14
15
16
17
18
19
20
21
22
Entry
R2
R3
Product
Yieldb (%)
a:b
0
57
50
74
42
29
20
23
23
42
47
66
2-Furyl
1
2
3
4
5
6
7
8
9
n-Pr
n-Bu
Me
Me
Ph
Me
Et
CO2Me
Me
n-Pr
n-Bu
t-Bu
n-C5H11
Ph
Ph
Ph
CO2Me
CO2Me
26
27
28
29
30
31
32
33
34
29
32
0
58
15
55
36c
41d
70e
—
—
—
51:49
—
65:35
69:31
—
2-Thienyl
trans-PhCH@CH
trans-PrCH@CH
trans-MeCH@CH
Me
Et
ClCH2
Cyclohexyl
PhCH2
PhCH2CH2
100:0
a
A mixture of an alkyne (0.5 mmol) and benzoic acid (5.0 mmol) was stirred at
a
100 °C for 17 h in the presence of 1a (0.01 mmol) and B(n-Bu)3 (0.15 mmol, 1 M THF
A mixture of 3-hexyne (0.5 mmol) and a carboxylic acid (5.0 mmol) was stirred
solution).
at 100 °C for 17 h in the presence of 1a (0.01 mmol) and B(n-Bu)3 (0.15 mmol, 1 M
b
Isolated yields.
E/Z = 16/84 (32a), 26/74 (32b).
E/Z = 50/50.
E/Z = 29/71.
THF solution).
c
b
Isolated yields.
E/Z = 14/86.
E/Z = 24/76.
d
c
e
d

250
N. Tsukada et al. / Tetrahedron Letters 52 (2011) 248–250
2 mol% 1a
N
N
N
N
30 mol% BnBu3
O
BBu3
R2
R3
Ph2P
PPh2
Ph2P
PPh2
+
Pd
Pd
Pd
Pd
O
H
Ph
OH
100 ºC
17 h
H
Tol
Tol
Tol
Tol
35
1a
ð5Þ
O
O
+ PhCO2H
— 2 Tol-H
R3
H
O
R2
H
O
+
Ph
Ph
R3
R2
+ alkyne
N
N
26-34b
26-34a
Ph2P
PPh2
Pd Pd
Et
O
While hydroarylation did not proceed without trialkylbor-
Z-3
anes,3a those are not essential for hydrocarboxylation. As indicated
previously, trialkylboranes could serve as a hydride source to
transform a hydroxo-bridged complex into a hydride-bridged com-
plex, which could be a true reaction intermediate.3a Actually, lith-
ium tri-tert-butoxyaluminum hydride can be used instead of
trialkylboranes.3b An acidic hydrogen atom of benzoic acid would
be a hydride source for generation of a hydride-bridged complex.8
Therefore hydrocarboxylation does not need additives essentially.
Hydroarylation,3a,b hydroalkenylation3c and hydroalkynyla-
Ph
Et
36
O
PhCO2H
path A
path B
N
N
N
N
Ph2P
Et
PPh2
Pd Pd
Ph2P
PPh2
Pd Pd
L
Et
O
Ph
O
O
L
Et
E/Z isomerization
O
tion3d catalyzed by
1 proceeded selectively via cis-addition,
38
Et
37
whereas the present hydrocarboxylation afforded mainly trans-ad-
ducts. To elucidate whether the trans-adducts were generated by
the isomerization of cis-adducts, the E/Z ratio of products was ob-
served at the early stage of several reactions. After 1 h, the reaction
of 3-hexyne with benzoic acid gave only the trans-adduct Z-3 in
low yield and with high stereoselectivity (Eq. 6). The E/Z ratio of
34 in the 1-h reaction of methyl butynoate was 29/71, which
was similar to that after 17 h (Table 3, entry 9). Next, the pure
E-isomer of 3, which was prepared by a different method,6d was
added to the reaction of 4-octyne with benzoic acid (Eq. 7). After
17 h, no isomerization of E-3 to Z-3 was observed. These results
show that the trans-adducts are not generated by isomerization
of the cis-adducts.
Ph
Scheme 1. Possible mechanisms.
isomerization of the alkenyl ligand,10 and protonated with benzoic
acid to afford Z-3. Nucleophilic attack of benzoate to alkyne from
the opposite side of palladium in 36 could also generate complex
38 directly (path B).
In summary, the dinuclear palladium complex 1 catalyzed the
hydrocarboxylation of internal alkynes with carboxylic acids to
predominantly yield trans-adducts. The precise reaction mecha-
nism and addition reactions of other O–H bonds to alkynes are un-
der investigation.
2 mol% 1a
Supplementary data
30 mol% BnBu3
O
R2
R3
+
Supplementary data (experimental details and product charac-
terizations) associated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2010.11.046.
Ph
OH
100 ºC
1 h
O
ð6Þ
O
R3
H
Ph
R2
References and notes
3 (R2 = R3 = Et); 21% (E/Z = <1/>99)
34a (R2 = Me, R3 = CO2Me); 37% (E/Z = 28/72)
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O
O
H
O
+
+
Pr
Ph
Pr
Ph
OH
Et
E-3
0.50 mmol
Et
0.25 mmol
5.0 mmol
ð7Þ
O
2 mol% 1a
30 mol% BnBu3
O
Pr
H
+
Ph
E-3
100 °C
17 h
Pr
98% recovery
4
Although there is little evidence for the mechanistic aspects at
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of 3-hexyne with benzoic acid is described in Scheme 1.3e As men-
tioned above, the reaction of 1a with tri-n-butylborane could give
hydride-bridged complex 35. Reductive elimination of toluene
from 35, followed by protonation of another tolyl ligand with ben-
zoic acid, would afford benzoate complex 36. Insertion of 3-hexyne
into Pd–Pd bond9 of 36 and reductive elimination on the right pal-
ladium center could result in cis-addition to give alkenyl palladium
complex 37 (path A). Complex 38 could be generated via E/Z
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