Re(CO)5Br-catalyzed addition of carboxylic acids to terminal alkynes: A high anti-Markovnikov and recoverable homogeneous catalyst

Article abstract of DOI:10.1021/jo049455n

The addition of carboxylic acids to terminal alkynes is efficiently catalyzed by the early transition-metal complex Re(CO)₅Br in toluene or n-heptane at 110 °C in an air atmosphere, affording the anti-Markovnikov adducts in good yields with high selectivity. In most cases, the reactions afford unusual Z-adduct predominantly. When n-heptane was used as solvent, Re(CO)₅Br can be partly recovered from the reaction mixture.

Full text of DOI:10.1021/jo049455n

TABLE 1. Effect of Solven t on th e Selectivity in th e
Ad d ition of 2a to 1a Ca ta lyzed by Re(CO)5Br a
Re(CO)5Br -Ca ta lyzed Ad d ition of
Ca r boxylic Acid s to Ter m in a l Alk yn es: A
High An ti-Ma r k ovn ik ov a n d Recover a ble
Hom ogen eou s Ca ta lyst
Ruimao Hua* and Xin Tian
Department of Chemistry, Tsinghua University,
Key Laboratory of Organic Optoelectronics & Molecular
Engineering of Ministry of Education,
Beijing 100084, China
yield of
selectivity of
entry
solvent
adducts (%)b
3a (%) (E/Z)c
ruimao@mail.tsinghua.edu.cn
Received April 2, 2004
1
2
3
4
5
6
7
8
9
n-heptane
toluene
CHCl2CHCl2
di-n-butyl ether
DMF
CH3COOC2H5
THF
acetone
72 (60)
73
69
73
30
35
20
4
3
99 (27/73)
100 (28/72)
100 (26/74)
95 (26/74)
94 (37/63)
50 (44/56)
40 (77/23)
29 (38/62)
62 (42/58)
Abstr a ct: The addition of carboxylic acids to terminal
alkynes is efficiently catalyzed by the early transition-metal
complex Re(CO)5Br in toluene or n-heptane at 110 °C in an
air atmosphere, affording the anti-Markovnikov adducts in
good yields with high selectivity. In most cases, the reactions
afford unusual Z-adduct predominantly. When n-heptane
was used as solvent, Re(CO)5Br can be partly recovered from
the reaction mixture.
CH3CN
a
Reactions were carried out with 2.0 mmol of 1a , 2.5 mmol of
2a , and 0.02 mmol of Re(CO)5Br in 1.0 mL of solvent at 110 °C
b
for 15 h. GC yields based on the amount of 1a used. Values in
parentheses are isolated yields. c Determined by GC.
Transition-metal-catalyzed addition of carboxylic acids
1 to terminal alkynes 2 is an efficient, atom-economic
method for the synthesis of 1-alkenyl esters. The addition
reaction often affords a mixture of three possible 1-alk-
enyl esters (one Markovnikov-type adduct and two anti-
Markovnikov-type E and Z adducts) (eq 1). Therefore, it
complexes. In most cases, the addition reactions either
gave the Markovnikov-type adduct as the major product
or afforded a mixture of three adducts with low selectiv-
ity. The aims of our study are to develop a simple,
efficient, and recoverable new catalyst system to catalyze
the addition of carboxylic acids to terminal alkynes with
high selectivity of the anti-Markovnikov adduct. In this
paper, we describe our findings of an early transition-
metal complex Re(CO)5Br-catalyzed addition reaction of
carboxylic acids to terminal alkynes with high selectivity
to afford anti-Markovnikov adducts. To the best of our
knowledge, this is the first example of early transition-
metal-catalyzed addition of carboxylic acids to alkynes.
We chose the reaction of phenyl acetylene 1a with
acetic acid 2a in the presence of Re(CO)5Br as a model
reaction to optimize the reaction conditions. The yields
of adducts were determined by gas chromatographic
analysis, using C16H34 as an internal standard. When a
solution of 2.0 mmol of 1a , 2.5 mmol of 2a , and 0.02 mmol
of Re(CO)5Br in 1.0 mL of n-heptane, in an air atmo-
sphere of a closed glass tube, was stirred at 110 °C for
15 h, the GC and GC-MS analyses of the reaction mixture
showed the formation of three adducts in a ratio of <1:
73:27 (retention time order) in 72% GC yield. The 1H
NMR spectroscopic data of the reaction mixture disclosed
that the addition reaction gave only a trace amount of
the Markovnikov adduct 4a (<1%). On the basis of the
coupling constants of the olefinic protons of the anti-
Markovnikov adducts, it was confirmed that the ratio of
Z-3a :E-3a was 73:27. These results are in accordance
with the GC quantitatively analytical data (Table 1, entry
is interesting and important to develop the catalyst
system for the high regio- and stereocontrol of the
addition reaction. Since Rotem and co-worker first re-
ported the example of the addition reaction in 1983 using
Ru3(CO)12 as catalyst,1 a variety of other catalytic systems
have been employed including Ru,2 Rh,3 Pd,4 and Ir5
(1) Rotem, M.; Shvo, Y. Organometallics 1983, 2, 1689-1691.
(2) (a) Mitsudo, T.; Hori, Y.; Watanabe, Y. J . Org. Chem., 1985, 50,
1566-1568. (b) Ruppin, C.; Dixneuf, P. H. Tetrahedron Lett. 1986, 27,
6323-6324. (c) Mitsudo, T.; Hori, Y.; Yamakawa, Y.; Watanabe, Y. J .
Org. Chem. 1987, 52, 2230-2239. (d) Rotem, M.; Shvo, Y. J . Orga-
nomet. Chem. 1993, 448, 189-204. (e) Doucet, H.; Martin-Vaca, B.;
Bruneau, C.; Dixneuf, P. H. J . Org. Chem. 1995, 60, 7247-7255. (f)
Bruneau, C.; Dixneuf, P. H. Chem. Commun. 1997, 507-512. (g)
Opstal, T.; Verpoort, F. Synlett 2002, 6, 935-941. (h) Melis, K.; Opstal,
T.; Verpoort, F. Eur. J . Org. Chem. 2002, 22, 3779-3784. (i) Melis,
K.; Verpoort, F. J . Mol. Catal. A: Chem. 2003, 194, 39-47. (j) Goossen,
L. J .; Paetzold, J .; Koley, D. Chem. Commun. 2003, 706-707. (k) Melis,
K.; Vos, D.; J acobs, P.; Verpoort, F. J . Organomet. Chem. 2003, 671,
131-136.
(3) Bianchini, C.; Meli, A.; Peruzzini, M.; Zanobini, F. Organome-
tallics 1990, 9, 1155-1160.
(4) Lu, X.; Zhu, G.; Ma, S. Tetrahedron Lett. 1992, 33, 7205-7209.
(5) Nakagawa, H.; Okimoto, S.; Sakaguchi, S.; Ishii, Y. Tetrahedron
Lett. 2003, 44, 103-106.
10.1021/jo049455n CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/20/2004
5782
J . Org. Chem. 2004, 69, 5782-5784

TABLE 2. Ad d ition of Ca r boxylic Acid s to Ter m in a l
Alk yn es Ca ta lyzed by Re(CO)5Br a
SCHEME 1. P r op osed Mech a n ism for th e
Ad d ition of Ca r boxylic Acid s to Ter m in a l Alk yn es
adducts;
selectivity of
entry
R
R′
yield (%)b
3 (%) (E/Z)c
1
C6H5
C6H5
CH3
CH3
3b; 70(67)
3c; 81(73)
3d ; 80 (51)
3e; 57 (50)
3f; 77 (45)
99 (13/87)
100 (24/76)
>99 (45/55)
98 (36/64)
>99 (44/56)
2
p-MeC6H4
n-C6H13
n-C6H13
n-C6H13
3d
4
C6H5
5d
6
t-C4H9
t-C4H9
NC(CH2)3
CH3OCO
CH3
CH3
CH3
CH3
3g; 78
99 (67/33)
f
96 (40/60)
100 (96/4)
7e
8
3g; 76f
3h ; 70 (65)
3i; 51 (33)
9
a
Reactions were carried out with 2.0 mmol of alkynes 1, 2.5
b
mmol of 2, and 0.02 mmol of Re(CO)5Br in 1.0 mL of toluene. GC
yields based on the amount of 1 used. The values in parentheses
d
are isolated yields. c Determined by GC. Reaction in n-heptane.
e Reaction in C6D6. f Yield and ratio of E:Z (67:33) were determined
by 1H NMR.
1). In addition, the ratio of Z-3a and E-3a could not be
changed by a prolonged reaction time (25 h).6
1-octyne with 2a , 2b, and acrylic acid furnished the anti-
Markovnikov adducts in good yields, and in all these
cases, the Z-adducts were predominant (Table 2, entries
3-5). However, in the case of the sterically congested 3,3-
dimethyl-1-butyne used, the addition reaction with 2a
took place to produce the E-adduct predominantly (Table
Table 1 summarizes the results of the effect of solvents
on the distribution of adducts in the reaction of 1a with
2a . The distribution of Markovnikov product and anti-
Markovnikov products, as well as the distribution of E-3a
and Z-3a stereoisomer, depends greatly on the nature of
the employed solvents. When toluene, 1,1,2,2-tetrachlo-
roethane, and di-n-butyl ether were used as solvents, the
addition reactions afforded the anti-Markovnikov adduct
3a exclusively (Table 1, entries 2 and 3) or with high
selectivity (Table 1, entry 4). The obtained yields and the
ratios of E-3a and Z-3a were similar to or the same as
those observed in n-heptane solvent. In contrast to the
nonpolar solvents, when the addition reactions were
carried out in polar solvents such as DMF, ethyl acetate,
THF, acetone, and acetonitrile, Re(CO)5Br showed low
catalytic activity (entries 5-9). In addition, except for
DMF, the use of polar solvents resulted in the increase
of the Markovnikov adduct 4a . In the cases of THF and
acetone, the addition reaction gave 4a as the main
product (Table 1, entries 7 and 8).
1
2, entry 6). A study of H NMR of the addition reaction
in C6D6 also confirmed the reversal of stereoselectivity
of adducts (Table 2, entry 7). In addition, the functional
group-bearing alkynes such as 5-hexynenitrile and meth-
yl propiolate also reacted with 2a to give the adducts 3h
and 3i in 70% and 51% yields, respectively (Table 2,
entries 8 and 9). I When methyl propiolate was employed,
the E-adduct was obtained in very high selectivity
(Z-3i: E-3i ) 4:96). Since methyl propiolate is an active
alkyne, we examined the reaction in the absence of
catalyst, and no addition reaction occurred at all.
Although the mechanism of the present rhenium-
catalyzed addition of carboxylic acids to alkynes remains
to be elucidated, one of the possible catalytic cycles
proposed is shown in Scheme 1. We suggest that the
catalytic reaction is initiated by the decarbonylation of
We also tested the catalytic activity of Re2(CO)10 in the
reaction of 1a with 2a under identical reaction conditions
(as shown in Table 1, entry 2); however, a very low yield
(ca. 10%) of adducts mixture was obtained.
Re(CO)5
Br to give 16-electron intermediate Re(CO) Br
4
(5).7 The formation of the vinylrhenium intermediates
(E)-7 and (Z)-7, which arise from the reaction of the
alkyne-coordinated intermediate 6 with carbonylic acid,
leads eventually to the formation of the anti-Markovnikov
adducts (Z)-3 and (E)-3. The stereoselective formation of
the adducts (Z)-3 or (E)-3 depends on the formation of
intermediate (E)-7 or (Z)-7, respectively. Intermediate
(E)-7 exists the steric repulsion between the substituent
R and the R′COO groups, while (Z)-7 has the steric
repulsion between the CO ligand and the R′COO group.
On the basis of the observation of adduct (Z)-3 obtained
predominantly in most cases, it seems that there is much
stronger steric repulsion between the CO ligand and the
R′COO group than between the R and the R′COO groups,
resulting in the favored formation of (E)-7. Accordingly,
The Re(CO)5Br-catalyzed addition reaction can be
readily applied to other terminal alkynes and carboxylic
acids. In n-heptane or toluene, all the addition reactions
afforded the anti-Markovnikov adduct exclusively or with
high selectivities. The results are summarized in Table
2. Addition of benzoic acid 2b to 1a afforded adducts 3b
in 70% GC yield with 99% of selectivity, and the ratio of
E-3b and Z-3b was 13:87 (Table 2, entry 1). p-Meth-
ylphenylacetylene reacted with 2a to give the adducts
3c in high yield with high selectivity as 1a did. Alkyl
alkynes also facilitated the present catalytic addition
reactions to afford the anti-Markovnikov adducts with
high selectivities. For example, the addition reactions of
(6) In the presence of Re(CO)5Br (1.0 mol %), heating a solution of
the isolated E-3a and Z-3a (E-3a /Z-3a ) 28/72) in n-heptane at 110
°C for 10 h could not change the ratio of E-3a and Z-3a . This observed
result indicated that the isomerization between E-3a and Z-3a could
not occur.
(7) The formation of 16-electron Re(CO)4Br (5) through the decar-
bonylation of Re(CO)5Br has already been reported: (a) J olly, P. W.;
Stone, F. G. A. J . Chem. Soc. 1965, 5259-5263. (b) Zingales, F.;
Sartorelli, U.; Canziani, F.; Raveglia, M. Inorg. Chem. 1967, 6, 154-
157.
J . Org. Chem, Vol. 69, No. 17, 2004 5783

it is reasonable to explain that when benzoic acid 2b was
used instead of acetic acid 1b, the ratios of the adducts
(Z)-3:(E)-3 were increased (Table 1, entry 2 vs Table 2,
entry 1; Table 2, entry 3 vs entry 4), since phenyl (R′ )
Ph, 2b) is bulkier than methyl (R′ ) Me, 1b).
On the other hand, when R is a bulky group (e.g. t-Bu),
the steric repulsion between the R and the R′COO group
becomes important. Therefore, in the case of 3,3-dimeth-
yl-1-butyne, the addition reaction gave (E)-3g predomi-
nantly. However, the highly selective formation of (E)-
3i from the reaction of methyl propiolate with 2a is not
clear.
Additionally, when the addition reaction was carried
out in n-heptane, Re(CO)5Br could be recovered partly
after the reaction. For example, if the reaction mixture
(shown in Table 2, entry 3) was cooled to ambient
temperature, the white crystals were formed.8 The IR
data of the isolated crystals were in accordance with
those of the authentic sample of Re(CO)5Br,9 and the
molecular structure of the crystals was unequivocally
confirmed by the X-ray structure analysis.10 Further-
more, the recovered Re(CO)5Br showed the same catalytic
activity and selectivity in n-heptane as fresh Re(CO)5Br
employed in the reactions of 1-octyne with acetic acid to
give 3d in 81% GC yield (Z-3d /E-3d ) 55:45).
In conclusion, we have developed the first early transi-
tion-metal complex Re(CO)5Br-catalyzed addition of car-
boxylic acids to terminal alkynes under an air atmo-
sphere. The catalytic procedure has three charac-
teristics: (1) the reactions take place in n-heptane or
toluene to give anti-Markovnikov adducts with high
selectivities; (2) in most cases, the addition reactions
afford unusual Z-adducts predominantly; and (3) the
catalyst Re(CO)5Br can be partly recovered after the
catalytic reactions in n-heptane solvent.
Ack n ow led gm en t. This work was supported by the
Tsinghua University for Scientific Research Program.
Su p p or tin g In for m a tion Ava ila ble: Detailed experi-
mental procedure, the ORTEP structure of the recovered Re-
(CO)5Br, and the charts of 1H, 13C NMR of 3a -i. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O049455N
(8) Re(CO)5Br could be recovered in 46-61% as precipitate with
n-heptane as solvent.
(10) For the ORTEP structure of Re(CO)5Br, see the Supporting
Information.
(9) IR(KBr): 2030, 2025, 1975, 600 cm-1
.
5784 J . Org. Chem., Vol. 69, No. 17, 2004