Regiocontrolled Ru-catalyzed addition of carboxylic acids to alkynes: Practical protocols for the synthesis of vinyl esters

Article abstract of DOI:10.1039/b211277a

The catalytic activity of commercially available, air and water stable ruthenium complexes in the addition of carboxylic acids to terminal alkynes was found to be drastically enhanced by the addition of small quantities of base. Moreover, the regioselecti

Full text of DOI:10.1039/b211277a

Regiocontrolled Ru-catalyzed addition of carboxylic acids to alkynes:
practical protocols for the synthesis of vinyl esters†
Lukas J. Goossen, Jens Paetzold and Debasis Koley
Max Planck Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany.
E-mail: goossen@mpi-muelheim.mpg.de; Fax: +49 208-306-2985; Tel: +49 208-306-2392
Received (in Cambridge, UK) 14th November 2002, Accepted 28th January 2003
First published as an Advance Article on the web 17th February 2003
The catalytic activity of commercially available, air and
water stable ruthenium complexes in the addition of
carboxylic acids to terminal alkynes was found to be
drastically enhanced by the addition of small quantities of
base. Moreover, the regioselectivity of the reaction can be
controlled by the choice of the base so that both the
order to identify factors that influence their catalytic activity.
Selected results are summarized in Table 1.
At a temperature of only 60 °C, commercially available
ruthenium compounds display almost no catalytic activity for
the desired transformation (Table 1, Entries 1–3). However, in
the presence of
((p-cumene)RuCl
a
catalyst generated in situ from
Markovnikov (Na
2
CO
3
) and the anti-Markovnikov products
2
)
2
6 and PPh , the addition proceeds with
3
(
DMAP) are now easily accessible in excellent selectivities.
high selectivity for the Markovnikov product 3a, though in
modest yields (Entry 4). Better yields are obtained when using
phosphines with strong p-acceptor ability such as tri-2-furyl
Vinyl esters such as vinyl acetates, acetoxystyrenes and vinyl
haloacetates are important substrates for polymerization reac-
3
phosphine ( = P(Fur) ) (Entries 5–7).
1
tions. Furthermore, they are utilized as mild acylating agents in
It was then investigated whether the addition of silver salts
with non-coordinating counterions would generate more active
cationic catalysts.13 However, among the silver salts tested,
2
3
the synthesis of various esters, amides or a-halo ketones and
are important intermediates in enzyme-catalyzed kinetic resolu-
tions of chiral alcohols. Other applications include cyclopropa-
4
3
solely AgNO showed an accelerating effect (Entries 8–10).
5
6
nations, [2 + 4]-, [2 + 2]-, and 1,3-dipolar cycloadditions,
Since the proposed catalytic cycle involves attack of the
asymmetric hydrogenation7 and hydroformylation8 reactions
carboxylate onto the alkyne coordinated to the ruthenium, we
2
and the conversion to enamides.9
reasoned that the presence of catalytic amounts of base should
increase the amount of carboxylate ions and might thus
facilitate the reaction more effectively. Indeed, simply by
adding a few mol% of sodium benzoate, the yields were
drastically increased. The addition of inorganic bases to the
reaction mixture had the same accelerating effect, best results
being obtained with sodium carbonate (Entries 11–13). The
reaction is insensitive to both air and water—a great advantage
for preparative applications (Entry 14).
Common syntheses of vinyl esters are transesterifications
10
with vinyl acetate or isopropenyl acetate, or O-acylations of
enolates.11 A particularly efficient entry to these compounds is
the ruthenium-catalyzed addition of carboxylic acids 1 to
alkynes 2 (Scheme 1). This was first performed by Rotem et al.
3
using Ru (CO)12 as the catalyst under rather harsh conditions,
12
giving rise mainly to the Markovnikov products. In the groups
of Mitsudo and Dixneuf, the reaction was further developed and
more active catalysts were discovered, e.g. bis(cyclooctadie-
nyl)Ru–phosphine–maleic anhydride or Ru(methallyl)
It was also found that bidentate
phosphines on the ruthenium reverse the selectivity of the
2
–phos-
phine combinations.1
3,14
Table 1 Ru-catalyzed addition of benzoic acid (1a) to hexyne (2a)
Conv. Sel. 3 Sel. 4
addition, so that instead of alk-1-en-2-yl esters 3, the (Z)-alk-
Entry Ru-Precursor Ligand
Additive
(%)
(%)
(%)
14
1-en-1-yl esters 4 are predominantly formed.
However, the practical value of this elegant transformation
1
2
3
4
5
6
7
8
9
0
1
2
RuCl
RuCl
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
3
3
—
—
—
PPh
3
P(Cy)
P(p-Cl-C H )
P(Fur)
P(Fur)
P(Fur)
P(Fur)
P(Fur)
P(Fur)
—
—
—
—
—
—
—
AgNO
AgClO
AgSbF
NaF
< 1
< 1
< 1
10
10
10
15
85
5
—
—
—
97
80
97
97
95
90
—
97
97
97
97
—
< 1
< 1
< 1
< 1
< 1
97
—
97
—
—
—
2
15
2
2
4
n.d.
—
2
2
2
2
—
98
98
99
99
99
2
remained limited for organic chemists, since the catalytic
activity of readily available ruthenium compounds is rather
low,15 and sufficiently active catalysts have to be especially
(PPh )
3 3
synthesized from sensitive organometallic compounds (i.e.
3
bis(cyclooctadienyl)Ru).13
6
4 3
3
3
3
3
3
3
We herein disclose a new catalyst system that is highly
effective, yet consists solely of easy-to-handle, commercially
available components and is thus particularly practical for
applications in synthetic chemistry.‡
We chose the reaction of benzoic acid 1a with 1-hexyne 2a
according to Scheme 1 (R1 = phenyl, R2 = n-butyl) as our
model system and screened various ruthenium complexes in
3
4
1
1
1
6
< 1
50
PhCOONa 95
Na CO3
Na
13
14
P(Fur)3
2
95
95
a
P(Fur)
P(Fur)
P(Fur)
P(Fur)
PPh
3
P(p-Cl-C
P(p-Cl-C
P(Fur)
P(Fur)
P(Fur)
3
3
3
3
2
CO
3
15
16
17
18
19
20
21
22
23
2,6-lutidine < 1
pyridine
DMAP
DMAP
DMAP
DMAP
Na
Na
Na
20
20
45
65
90
95
< 1
95
6
6
6
6
6
6
6
H
H
4
)
)
3
b
c
d
e
6
4
3
3
3
3
2
2
2
CO
CO
CO
3
3
3
—
2
Scheme 1 Addition of carboxylic acids to terminal alkynes.
Conditions: 1.00 mmol benzoic acid, 1.30 mmol 1-hexyne, 0.01 mmol Ru-
precursor, 0.02 mmol ligand, 0.04 mmol additive, toluene, 60 °C, 16 h. 10
mmol water, no argon, 25 °C, 72 h. 0.03 mmol ligand. 1,2-
Dichloroethane. d NMP. e Nonanoic acid, no solvent.
a
†
We thank Prof. Dr. M. T. Reetz for generous support and constant
encouragement, and gratefully acknowledge the DFG, the FCI, and the
BMBF for financial support.
b
c
7
06
CHEM. COMMUN., 2003, 706–707
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In the presence of inorganic bases, the reactions showed high
selectivities for the Markovnikov product 3a. To our surprise,
this selectivity was reversed when organic bases, e.g. pyridines,
were added (Entries 15–17). In the presence of (4-dimethylami-
no)pyridine (DMAP), the selectivity for the (Z)-anti-Markovni-
kov product 4a was 98 to 99%. Only trace quantities of 3a and
the E-isomer 5a were observed. This effect may be rationalized
by assuming that DMAP coordinates to the ruthenium, giving
pressure, so that no high-pressure equipment is required for the
preparation of the synthetically particularly useful isopropenyl
esters.4
Overall, we have developed highly efficient catalyst systems
for both the Markovnikov and the anti-Markovnikov addition of
carboxylic acids to terminal alkynes. The catalysts are gen-
erated in situ from air- and water-stable compounds that are
commercially available at low cost. Thus, important drawbacks
of this elegant transformation have been overcome.
rise to a complex with similar selectivities to ruthenium
compounds with chelating ligands.1
4,16
For the anti-Markovni-
kov reaction variant, P(p-Cl-C
than P(Fur) (Entries 17–20).
6
H
4
)
3
was slightly more effective
Notes and references
3
‡
0
Method A: Benzoic acid (588 mg, 5.00 mmol) and Na
.08 mmol) were suspended in toluene (16 ml). Subsequently, a solution of
(12.2 mg, 0.02 mmol) and tri(2-furyl)phosphine (9.20
2 3
CO (9.40 mg,
Toluene, chloroform and 1,2-dichloroethane are suitable
solvents for both reaction variants, while more strongly
coordinating solvents lower the turnover rates (Entries 13, 21
and 22). When using liquid carboxylic acids, the reaction can
also be carried out successfully without solvent (Entry 23).
After having identified highly active catalyst systems for both
Markovnikov and anti-Markovnikov additions of carboxylic
acids to 1-alkynes, we investigated the scope of our protocols
using various carboxylic acids in combination with several
alkynes. Selected results are summarized in Table 2. Electron-
rich and electron-poor alkyl, aryl, and heteroaryl carboxylic
acids give excellent yields with both catalyst systems. Even
sterically hindered carboxylic acids are converted and a variety
of functionalities including esters, ethers, aldehydes, carba-
mates, and even hydroxyl groups are tolerated.
((p-cumene)RuCl
)
2 2
mg, 0.04 mmol) in toluene (4 ml), and 1-hexyne (710 ml, 6.50 mmol) were
added. The reaction mixture was heated to 50 °C. After complete conversion
(GC), usually 16 h, the mixture was cooled and filtered over a small plug of
silica gel. The solvent was removed and the crude mixture was purified by
Kugelrohr distillation at 120 °C/0.1 mbar, yielding product 3a (950 mg,
9
3%, isomeric purity > 96%) as a colorless liquid.
Method B: A solution of ((p-cumene)RuCl (30.6 mg, 0.05 mmol),
tri(p-Cl-C )phosphine (54.8 mg, 0.15 mmol) and DMAP (24.4 mg, 0.20
2 2
)
6 4
H
mmol) in dry toluene (4 ml) was added to a solution of benzoic acid (588
mg, 5.00 mmol) and 1-hexyne (710 ml, 6.50 mmol) in dry toluene (16 ml).
The mixture was stirred for 16 h at 60 °C and worked up as above, yielding
4
a (908 mg, 89%, isomeric purity > 98 %).
H-, 13C-NMR, HRMS) was identical to that
All spectroscopic data (
reported in the literature for the (Z)-isomer.
1
While the Markovnikov addition of N-protected a- and b-
amino acids proceeds smoothly, the a-amino acids give no
conversion in the anti-Markovnikov reaction variant. Further
experiments suggested that this may be due to the high C–H
acidity of a-amino acids.
1
2
3
J. P. Monthéard, M. Camps, G. Seytre, J. Guillet and J. C. Dubois,
Angew. Makromol. Chem., 1978, 72, 45–55.
Recent review: E. Bruneau, M. Neveux, Z. Kabouche, C. Ruppin and P.
H. Dixneuf, Synlett, 1991, 755–763.
(a) A. D. Cort, J. Org. Chem., 1991, 56, 6708–6709; (b) R. C. Cambie,
R. C. Hayward, J. L. Jurlina, P. S. Rutledge and P. D. Woodgate, J.
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S. Stavber, B. Sket, B. Zajc and M. Zupan, Tetrahedron, 1989, 45,
6003–6010.
Various other terminal alkynes were converted in good yields
and mostly in good selectivities. It is especially worth
mentioning that gaseous propyne smoothly reacts at ambient
Table 2 Scope of the Markovnikov and the anti-Markovnikov addition
4
(a) For examples see: T. Ema, S. Maneo, Y. Takaya, T. Sakai and M.
Utaka, J. Org. Chem., 1996, 61, 8610–8616; (b) M. Kawasaki, M. Goto,
S. Kawabata and T. Kometani, Tetrahedron: Asymmetry, 2001, 12,
586–596.
R1
R2
Method Prod.
Yield (%) Sel 3+4
a
Phenyl
o-Tolyl
p-MeO-C
n-C
n-C
n-C
n-C
n-C
4
4
4
4
4
4
4
4
4
4
4
4
H
H
H
H
H
H
H
H
H
H
H
H
9
9
9
9
9
9
9
9
9
9
9
9
A
B
A
B
A
B
A
3a
4a
3b
4b
3c
4c
3d
4d
3e
4e
3f
93
89
86
93
88
90
87
80
94
87
95
94
61
72
86
86
83
74
95
78
70
46
82
< 5
88
99
99
76
88
68
30+1
1+50
35+1
1+50
15+1
1+50
10+1
1+50
30+1
1+50
24+1
1+50
15+1
1+50
50+1
1+50
22+1
1+50
30+1
1+50
14+1
1+50
14+1
n.d.
5 (a) A. Demonceau, E. Saive, Y. de Froidmont, A. F. Noels and A. J.
Hubert, Tetrahedron Lett., 1992, 33, 2009–2012; (b) W. B. Motherwell
and L. R. Roberts, J. Chem. Soc., Chem. Commun., 1992, 1582–1583.
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4309–4311; (b) L. F. Tietze, A. Montenbruck and C. Schneider, Synlett,
1994, 509–510; (c) A. Wexler, R. J. Balchunis and J. S. Swenton, J.
Chem. Soc., Chem. Commun., 1975, 601–602; (d) M. C. Pirrung and Y.
R. Lee, Tetrahedron Lett., 1994, 35, 6231–6234.
7 K. E. Koenig, G. L. Bachman and B. E. Vineyard, J. Org. Chem., 1980,
45, 2362–2365.
8 (a) N. Sakai, K. Nozaki, K. Mashima and H. Takaya, Tetrahedron:
Asymmetry, 1992, 3, 583–586; (b) C. G. Arena, F. Nicolo, D. Drommi,
G. Bruno and F. Faraone, J. Chem. Soc., Chem. Commun., 1994,
2251–2252.
9 (a) P. H. Dixneuf, C. Bruneau and S. Dérien, Pure Appl. Chem., 1998,
70, 1065; (b) H. Doucet, C. Bruneau and P. H. Dixneuf, Synlett, 1997,
807–808.
10 J. March, Advanced Organic Chemistry, 3rd ed., John Wiley & Sons,
New York, pp. 351–353.
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43, 2601–2608; (c) J. Libman and Y. Mazur, Tetrahedron, 1969, 25,
1699–1706.
12 M. Rotem and Y. Shvo, Organometallics, 1983, 2, 1689–1691.
13 (a) T. Mitsudo, Y. Hori and Y. Watanabe, J. Org. Chem., 1985, 50,
1566–1568; (b) T. Mitsudo, Y. Hori, Y. Yamakawa and Y. Watanabe,
J. Org. Chem., 1987, 52, 2230–2239.
6
H
4
b
p-H(CO)-C
6
H
4
c
B
2
1
-Thienyl
A
B
A
B
A
B
A
B
A
B
A
-Me-pyrrol-2-yl n-C
4f
b
HO-n-C11
m-AcO-C
-C
-C
H
22
n-C
n-C
n-C
n-C
n-C
n-C
3g
4g
3i
4i
3j
6 4
H
6
C H
5
2
H
4
4j
p-CF
3
6
H
4
3k
4k
3l
c
B
b
Cbz-NHCH
Cbz-NHCH
Phenyl
2
CH
2
A
B
A
B
A
B
A
B
A
4l
b
d
2
3m
4m
3n
4n
3o
4o
3p
4p
Phenyl
CH
t-Butyl
3+2
1+50
22+1
1+50
10+1
1+50
Phenyl
3
Phenyl
14 (a) H. Doucet, J. Höfer, C. Bruneau and P. H. Dixneuf, J. Chem. Soc.,
Chem. Commun., 1993, 850–851; (b) H. Doucet, B. Martin-Vanca, C.
Bruneau and P. H. Dixneuf, J. Org. Chem., 1995, 60, 7247–7255.
c
B
Conditions: A: 5.00 mmol acid, 6.50 mmol alkyne, 0.02 mmol 6, 0.04 mmol
P(Fur) , 0.08 mmol Na CO , toluene, 50 °C, 16 h; B: 5.00 mmol acid, 6.50
mmol alkyne, 0.05 mmol ((p-cumene)RuCl 6, 0.15 mmol P(p-Cl-C
1
5 (a) H. Doucet, N. Derrien, Z. Kabouche, C. Bruneau and P. H. Dixneuf,
J. Organomet. Chem., 1997, 551, 151–157; (b) C. Bruneau, M. Neveux-
Duflos and P. H. Dixneuf, Green Chem., 1999, 1, 183–185.
3
2
3
)
2 2
6 4 3
H ) ,
a
b
c
0
1
3
.20 mmol DMAP, toluene, 60 °C, 16 h. Isomer 5 < 1 %. In CHCl . In
d
16 In the ESI-MS of the reaction mixture, a signal for a Ru–p-cumene–
benzoate–hexyne–DMAP complex was detected at m/z = 561.3.
,2-dichloroethane, 80 °C. 70 °C.
CHEM. COMMUN., 2003, 706–707
707