Halide ions as a highly efficient promoter in the Ru-catalyzed hydroesterification of alkenes and alkynes

Article abstract of DOI:10.1021/ol061753e

(Chemical Equation Presented) The presence of catalytic amounts of halide salts was found to enhance dramatically the reaction efficiency in the Ru-catalyzed hydroesterification of alkenes and alkynes using a chelating 2-pyridylmethyl formate by lowering

Full text of DOI:10.1021/ol061753e

ORGANIC
LETTERS
2006
Vol. 8, No. 19
4355-4358
Halide Ions as a Highly Efficient
Promoter in the Ru-Catalyzed
Hydroesterification of Alkenes and
Alkynes
Eun Ju Park, Ji Min Lee, Hoon Han, and Sukbok Chang*
Center for Molecular Design and Synthesis (CMDS), Department of Chemistry and
School of Molecular Science (BK21), Korea AdVanced Institute of Science and
Technology, Daejeon 305-701, Republic of Korea
sbchang@kaist.ac.kr
Received July 17, 2006
ABSTRACT
The presence of catalytic amounts of halide salts was found to enhance dramatically the reaction efficiency in the Ru-catalyzed hydroesterification
of alkenes and alkynes using a chelating 2-pyridylmethyl formate by lowering the reaction temperature. On the basis of IR and NMR studies,
the halide effect on the reaction is mainly attributed to the facile dissociation of the trirutheniumcarbonyl precursor into the presumed active
metal species. With this milder condition, the substrate scope has been significantly broadened.
Functionalization of unsaturated compounds into carbonyl-
containing molecules is an area of great interest.1 We recently
reported one notable example of those functionalizations by
virtue of Ru3(CO)12 catalyst in the hydroesterification and
hydroamidation of double and triple bonds using 2-pyridyl-
methyl formate (1, eq 1).2
with a range of substrates. Additionally, the reaction does
not require external CO atmosphere and it can be run even
in solvent-free conditions. The chelating auxiliary, 2-pyridine-
methanol, can be quantitatively recovered after hydrolysis
of the produced esters, thus offering additional merits.
Despite these advantages, the reaction usually requires
relatively high temperatures and a large excess of substrates,
which provide difficulties for making this one-carbon ho-
mologating protocol more practical. Although several aspects
may be considered to improve the reaction conditions,4 we
envisioned that the generation of catalytically more active
The reaction is believed to proceed via a chelation-assisted
pathway,3 and it exhibits excellent efficiency and selectivity
(2) (a) Ko, S.; Na, Y.; Chang, S. J. Am. Chem. Soc. 2002, 124, 750-
751. (b) Na, Y.; Ko, S.; Hwang, L. K.; Chang, S. Tetrahedron Lett. 2003,
44, 4475-4478. (c) Ko, S.; Lee, C.; Choi, M.-G.; Na, Y.; Chang, S. J.
Org. Chem. 2003, 68, 1607-1610. (d) Ko, S.; Han, H.; Chang, S. Org.
Lett. 2003, 5, 2687-2690.
(3) For some selected examples, see: (a) Murai, S.; Kakiuchi, F.; Sekine,
S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N. Nature 1993, 366,
529-531. (b) Itami, K.; Koike, T.; Yoshida, J.-i. J. Am. Chem. Soc. 2001,
123, 6957-6958. (c) Han, H.; Bae, I.; Yoo, E. J.; Lee, J.; Do, Y.; Chang,
S. Org. Lett. 2004, 6, 4109-4112. (d) Ko, S.; Kang, B.; Chang, S. Angew.
Chem., Int. Ed. 2005, 44, 455-457.
(1) For selected examples of hydroacylation of alkenes, see: (a) Lochow,
C. F.; Miller, R. G. J. Am. Chem. Soc. 1976, 98, 1281-1283. (b) Marder,
T. B.; Roe, D. C.; Milstein, D. Organometallics 1988, 7, 1451-1453. (c)
Bosnich, B. Acc. Chem. Res. 1998, 31, 667-674. (d) Tanaka, K.; Fu, G.
C. J. Am. Chem. Soc. 2001, 123, 11492-11493. (e) Sato, Y.; Oonishi, Y.;
Mori, M. Angew. Chem., Int. Ed. 2002, 41, 1218-1221. (f) Tanaka, M.;
Sakai, K.; Suemune, H. Curr. Org. Chem. 2003, 7, 353-367. (g) Kakiuchi,
F.; Chatani, N. Top. Organomet. Chem. 2004, 11, 45-79.
10.1021/ol061753e CCC: $33.50
© 2006 American Chemical Society
Published on Web 08/24/2006

species via the facile dissociation of the trirutheniumcarbonyl
cluster might be a key to overcome the present drawback.
Herein, we report our findings that certain halide additives
greatly improve the reaction conditions, thereby enabling the
hydroesterification to be carried out under much milder
conditions with a more diverse range of substrates.5
We embarked on the study of additive effects6 in a test
reaction of 3,3-dimethyl-1-butene (1.2 equiv) with 2-pyridyl-
methyl formate (1) by the action of Ru3(CO)12 catalyst in
DMF at 70 °C (Table 1).7 Addition of amine bases or acids
additives such as NH4PF6,8 t-BuOH, Ph3P, or Ph3PO dis-
played deteriorative effects (entries 6-9).
On the other hand, certain halide salts dramatically im-
proved the efficiency of the hydroesterification, the extent
of which was varied depending on the countercations. While
the lithium salt of chloride displayed a marginal improve-
ment, the use of bromide or iodide salts resulted in notable
activation effects (entries 10-12). Interestingly, in the case
of organic ammonium salts, the halide effect was most signif-
icant with iodide anion (entries 13-15). The additive effects
turned out to be less effective below 70 °C (entry 16).
There are several precedents in which a series of new inter-
exchangeable ruthenium species are generated when a solu-
tion of Ru3(CO)12 is treated with halide ions. For example,
it is known that Ru3(CO)12 reacts readily with iodide ion to
form initially [Ru3(CO)11(I)]-, which is next converted to a
bridging species [Ru3(CO)10(µ2-I)]- and then to [Ru3(CO)9-
(µ3-I)]- having a triply bridged iodide ligand.9 Interestingly,
Dombek reported that iodide reacts with Ru3(CO)12 under
normal H2 or H2/CO atmosphere to afford two main
ruthenium species, [HRu3(CO)11]- and [Ru(CO)3I3]-.6 He
further demonstrated that a combination of these two adducts
is required for achieving an optimal activity in the hy-
drogenation of CO to produce ethylene glycol with the
Ru3(CO)12/I- catalyst precursor system. Since Ru3(CO)12 is
in equilibrium with its monomeric Ru(CO)5 species only
under high CO pressure,10 it is reasonable, in our case, to
rule out a possibility that the added halide ions directly
dissociate the trinuclear cluster into monomeric species under
the present hydroesterification conditions.
Table 1. Additive Effects in the Hydroesterification Reactiona
entry
additive
Et3N
2,6-lutidine
CH3CO2H
NMO
NH4 PF6
t-BuOH
PPh3
Ph3PO
LiCl
LiBr
LiI
Bu4NCl
Bu4NBr
Bu4NI
convb (%)
yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
12
<5
10
13
25
16
10
<5
10
40
90
>98
13
30
>98
10
10
<5
<5
<5
15
10
<5
<5
6
20
85
95
12
30
95
8
When we treated a solution of Ru3(CO)12 in THF with
LiI at 60 °C, IR spectroscopy showed that the original
carbonyl peaks of Ru3(CO)12 were gradually replaced with
a series of new vibrational bands at 2043, 1991, and 1950
cm-1 (Figure 1). In contrast, no spectroscopic change was
Bu4NI (50 °C)
a Alkene (0.48 mmol), 1 (0.4 mmol), Ru3(CO)12 (5 mol %), and additive
(15 mol %) in DMF (0.2 mL). b Conversion and yield were determined by
1H NMR relative to an internal standard.
(15 mol %) showed rather inhibitory effects (entries 2-4).
While Floreancig et al. showed that the addition of N-
methylmorpholine N-oxide (NMO) resulted in a rate en-
hancement in the hydroesterification using 1,4 it did not
greatly improve the reaction efficiency under our conditions
(entry 5). In addition, the employment of various other
(4) For an intuitive mechanistic work on the hydroesterification of olefins
using 1, see: (a) Wang, L.; Floreancig, P. E. Org. Lett. 2004, 6, 569-572.
(b) Wang, L.; Floreancig, P. E. Org. Lett. 2004, 6, 4207-4210.
(5) For selected examples of halide additive effects in catalytic reactions,
see: (a) Lavigne. G.; Kaesz, H. D. J. Am. Chem. Soc. 1984, 106, 4647-
4648. (b) Dombek, B. D. Organometallics, 1985, 4, 1707-1712. (c) Kiso,
Y.; Tanaka, M.; Nakamura, H.; Yamasaki, T.; Saeki, K. J. Organomet.
Chem. 1986, 312, 357-364. (d) Yoshida, S.-I.; Mori, S.; Kinoshita, H.;
Watanabe, Y. J. Mol. Catal. 1987, 42, 215-227. (e) Lautens, M.; Fagnou,
K.; Yang, D. J. Am. Chem. Soc. 2003, 125, 14884-14892. (f) Dahle´n, A.;
Hilmersson, G. Eur. J. Inorg. Chem. 2004, 3393-3403. (g) Ruck, R. T.;
Zuckerman, R. L.; Krska, S. W.; Bergman, R. G. Angew. Chem., Int. Ed.
2004, 43, 5375-5377.
(6) For selected examples showing that the addition of certain salts to a
solution of rutheniumcarbonyl complexes results in catalytically more active
species, see: (a) Dombek, B. D. J. Am. Chem. Soc. 1981, 103, 6508-
6510. (b) Knifton, J. F. J. Am. Chem. Soc. 1981, 103, 3959-3961. (c)
Dombek, B. D. J. Organomet. Chem. 1983, 250, 467-483. (d) Dombek,
B. D. J. Organomet. Chem. 1989, 372, 151-161. (e) Lavigne, G. Eur. J.
Inorg. Chem. 1999, 917-930. (f) Fagnou, K.; Lautens, M. Angew. Chem.,
Int. Ed. 2002, 41, 26-47.
Figure 1. IR spectra of a mixture of Ru3(CO)12 and LiI (3 equiv)
in THF at 60 °C.
detected when a Ru3(CO)12 solution was treated with
additives possessing no promoting effects such as NH4PF6.11
Interestingly, several characteristic IR peaks obtained from
4356
Org. Lett., Vol. 8, No. 19, 2006

the presently employed system of Ru3(CO)12/LiI are well
matched with those of the reported complex [Ru3(CO)9-
(µ3-I)][N(PPh3)2], albeit missing a bridging carbonyl peak
near 1793 cm-1.9 The IR studies imply that all of the CO’s
from the present combination of Ru3(CO)12 and LiI are
terminal. Although further studies remain to elucidate the
exact structure of the catalytically active species in our case,12
this observation suggests that the main reason for the present
improvement of the reaction conditions by virtue of additives
is probably due to the facile CO ligand dissociation of the
rutheniumcarbonyl cluster upon the addition of halide ions.
Table 2. Hydroesterification of Various Olefinic Substratesa
In addition, when we treated a solution of Ru3(CO)12 and
2-pyridylmethyl formate (1) in DMF-d7 with tetrabutylam-
1
monium iodide (2) at 70 °C, it was observed by H NMR
that two peaks appeared gradually at -12.5 and -15.7 ppm,
which are assignable to ruthenium hydride presumably
generated by an oxidative addtion of formyl C-H bond of
1 with ruthenium metal.13 Interestingly, the intensity of the
peaks was maintained without much diminution even after
12 h, suggesting that the presence of halides may also help
increase the half-life of the emerging rutheniumcarbonyl
hydride species, which subsequently insert into the unsatur-
ated C-C bonds.4
The halide additive effects turned out to be general, and
a wide range of alkenes were efficiently converted to the
corresponding one-carbon elongated esters under the opti-
mized conditions (Table 2). The additive effects are often
moderate with highly reactive alkenes such as terminal or
strained internal olefins. With those olefins, excellent product
yileds could be obtained even when only 1.2 equiv of
substrates were employed by virtue of Bu4NI salt (2) (entries
1-10).
(7) Lavigne and co-workers showed that preformed ruthenium carbonyl
halide species [N(PPh3)2]2[Ru3(µ-Cl)2(CO)11] could be used as a good
catalyst precursor in the hydroesterification of ethylene using methyl formate
at 160 °C: (a) Lavigne, G.; Lugan, N.; Kalck, P.; Soulie´, J. M.; Lerouge,
O.; Saillard, J. Y.; Halet, J. F. J. Am. Chem. Soc. 1992, 114, 10669-10670.
(b) Lugan, N.; Lavigne, G.; Soulie´, J. M.; Fabre, S.; Kalck, P.; Saillard, J.
Y.; Halet, J. F. Organometallics 1995, 14, 1712-1731.
(8) For selected examples of NH4PF6 additive effects in Ru3(CO)12
catalysis, see: (a) Tokunaga, M.; Eckert, M.; Wakatsuki, Y. Angew. Chem.,
Int. Ed. 1999, 38, 3222-3225. (b) Shimada, T.; Yamamoto, Y. J. Am. Chem.
Soc. 2003, 125, 6646-6647. (c) Yi, C. S.; Yun, S. Y.; Guzei, I. A. J. Am.
Chem. Soc. 2005, 127, 5782-5783.
(9) (a) Han, S.-H.; Geoffroy, G. L.; Dombek, B. D.; Rheingold, A. L.
Inorg. Chem. 1988, 27, 4355-4361. (b) Rivomanana. S.; Lavigne. G.;
Lugan, N.; Bonnet. J.-J. Organometalllics 1991, 10, 2285-2297.
(10) (a) Bor, G. Pure Appl. Chem. 1986, 58, 543-552. (b) Koelliker,
R.; Bor, G. J. Organomet. Chem. 1991, 417, 439-451.
a Olefin (0.48 mmol in entries 1-10 and 1.2 mmol in entries 11-22), 1
(0.4 mmol), and 2 (15 mol %) in the indicated solvent (0.2 mL). b Isolated
yield and ratio of linear/branced isomer of crude mixture. c Only exo-product
was generated. d An equal mixture of two diastereomers. e Ratio of R- to
â-ester. f Ratio of 1- to 2-carboxylate.
(11) See the Supporting Information for details.
(12) Several additional examples have been reported on the halide
promotion effects in Ru3(CO)12-catalyzed reactions. Hydrogenation of
carbon dioxide: (a) Tominaga, K.-i.; Sasaki, Y. J. Mol. Catal. A: Chem.
2004, 220, 159-165. Oxonation of olefins: (b) Knifton, J. F. J. Mol. Catal.
1988, 47, 99-116. Alkoxycarbonylation: (c) Hidai, M.; Koyasu, Y.;
Chikanari, K.; Uchida, Y. J. Mol. Catal. 1987, 40, 243-254. Hydroformy-
lation of olefins with CO2: (d) Keister, J. B.; Gentile, R. J. Organomet.
Chem. 1981, 222, 143-153. Homologation of methyl formate: (e) Ragaini,
F.; Cenini, S. J. Mol. Catal. A: Chem. 2000, 161, 31-38. Reductive
carbonylation of aromatic nitro compounds: (f) Pizzotti, M.; Cenini, S.;
Quici, S.; Tollari, S. J. Chem. Soc., Perkin Trans. 2. 1994, 913-917.
(13) (a) Ayllon, J. A.; Sayers, S. F.; Sabo-Etienne, S.; Donnadieu, B.;
Chaudret, B.; Clot, E. Organometallics 1999, 18, 3981-3990. (b) Grumbine,
S. K.; Mitchell, G. P.; Straus, D. A.; Tilley, T. D.; Rheingold, A. L.
Organometallics 1998, 17, 5607-5619. (c) Na, Y.; Chang, S. Org. Lett.
2000, 2, 1887-1889. (d) Lee, M.; Ko, S.; Chang, S. J. Am. Chem. Soc.
2000, 122, 12011-12012.
The regioselectivity for the formation of linear to branched
isomeric ester was not noticeably changed by the presence
of halide additives (entries 3, 4 and 7, 8), suggesting that
the main catalytic cycle is not altered by the promoter.4
Moreover, the nature of halide ions does not seem to have
much influence on the regioselectivity of the reaction. For
example, when less effective LiCl or LiBr was employed as
an additive in the reaction of 1-hexene, the regioselectivity
of the linear/branched products was observed to be 3.7:1 and
Org. Lett., Vol. 8, No. 19, 2006
4357

15-18). When 3,4-dihydro-2H-pyran was employed, tet-
rahydropyran carboxylates were produced in a satisfactory
yield as a mixture of 2- and 3-regioisomer (R-/â-ester, 82:
18) only in the presence of of 2 at 110 °C (entries 19 and
20). Likewise, the similar promotion effect of 2 was observed
in the reaction of 1,2-dihydronaphthalene (entries 21 and 22).
Interestingly, 2-carboxylate was generated as a major isomer
relative to 1-carboxylate (R-/â-ester, 15:85).
Table 3. Hydroesterification of Dienes and Alkynesa
The halide additive effect was next investigated in the Ru-
catalyzed hydroesterification of dienes and alkynes with
2-pyridylmethyl formate (1). It was found that the reaction
of those compounds efficiently proceeded only in the
presence of ammonium iodide salt in aprotic polar solvents
(Table 3). For example, a regioselective hydroesterification
of 4-vinylcyclohexene took place more smoothly by the
combined action of Ru3(CO)12 and Bu4NI catalyst at 70 °C
(entries 1 and 2). The promotion effects were exerted more
dramatically on bulkier diolefinic substrates (entries 3-6).
When alkynes were examined, a similar additive effect of
iodide ion was also observed as demonstrated by entries
7-10.
In summary, we have demonstrated that certain halides
induce dramatic enhancement effects in the Ru3(CO)12-
catalyzed hydroesterification of alkenes and alkynes using
2-pyridylmethyl formate, thus enabling the reaction to be
carried out under milder conditions with a much broader
substrate scope. The promotion effect is mainly attributed
to the facile dissociation of CO ligand from the ruthenium-
carbonyl precursor catalyst initiated by the added halides. It
is anticipated that this study can lead to more diverse
synthetic applications using the developed milder procedure
as an one-carbon homologation approach.
a Substrate (1.2 mmol), 1 (0.4 mmol), Ru3(CO)12 (5 mol %), 2 (15 mol
%) in the indicated solvent (0.2 mL). b Isolated yield. c Two diastereomers
were produced almost as an equal mixture. d Ratio of two regioisomers A/B
1
determined by H NMR of crude mixture.
4.0:1, respectively, which are in a similar range compared
to that with the LiI additive (4.0:1). As anticipated, the halide
effect was more dramaticially exerted with less reactive olefin
substrates. For example, while only negligible conversion
was observed with cyclohexene or 5-methyl-5-hexen-2-one
without additives, excellent yields were obtained in the
presence of Bu4NI (entries 11-14). In addition, hydroesteri-
fication of â-pinene and R-methylstyrene took place smoothly
only in the presence of the halide additive leading to good
to excellent yields of the corresponding esters (entries
Acknowledgment. Dedicated to Professor Sunggak Kim
on the occasion of his 60th birthday. This research was
supported by Grant No. (R01-2005-000-10381-0) from the
Basic Research Program and by the CMDS at KAIST.
Supporting Information Available: General procedures,
data, and spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
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