Oxygen-promoted Pd(II) catalysis for the coupling of organoboron compounds and olefins

Article abstract of DOI:10.1021/ol034458s

(Matrix presented) Reported herein is a mild and efficient Pd(ll) catalysis, leading to the formation of carbon-carbon bonds between a broad spectrum of organoboron compounds and alkenes. Molecular oxygen was employed to reoxidize the resultant Pd(0) species back to Pd(ll) during catalytic cycles. This oxygen protocol promoted the desired Pd(ll) catalysis, whereas it retarded competing Pd(0) catalytic pathways such as Heck or Suzuki couplings.

Full text of DOI:10.1021/ol034458s

ORGANIC
LETTERS
2
003
Vol. 5, No. 13
231-2234
Oxygen-Promoted Pd(II) Catalysis for
the Coupling of Organoboron
Compounds and Olefins
2
Young Chun Jung, Rajesh Kumar Mishra, Cheol Hwan Yoon, and
Kyung Woon Jung*
Department of Chemistry (SCA 400), UniVersity of South Florida,
4202 E. Fowler AVenue, Tampa, Florida 33620-5250
kjung@chuma.cas.usf.edu
Received March 15, 2003 (Revised Manuscript Received May 16, 2003)
ABSTRACT
Reported herein is a mild and efficient Pd(II) catalysis, leading to the formation of carbon−carbon bonds between a broad spectrum of organoboron
compounds and alkenes. Molecular oxygen was employed to reoxidize the resultant Pd(0) species back to Pd(II) during catalytic cycles. This
oxygen protocol promoted the desired Pd(II) catalysis, whereas it retarded competing Pd(0) catalytic pathways such as Heck or Suzuki couplings.
6
The Heck reaction is one of the most widely used standard
reagents and their byproducts are highly toxic and difficult
7
tools for carbon-carbon bond-forming reactions in organic
to remove. Comparatively, organoboron reagents are less
toxic, stable in air, and easily accessible; thus, it is
1
8
synthesis. In addition to the conventional Heck reaction of
unsaturated compounds with organic halides and triflates as
an electrophile, the use of nucleophilic organometallic
worthwhile to explore their synthetic utility for the Heck-
type reactions. Uemura reported a Pd(0)-catalyzed cross-
coupling of boronic acids and alkenes via oxidative addition
2
3
reagents such as organosilanes, organoantimony, and or-
4
9
ganotins have attracted much attention. Our group has also
of Pd(0) to a carbon-boron bond. In this case, the reactions
reported an improved method for the aryl-alkenyl coupling
required long reaction times (20-38 h) and acetic acid as a
solvent. On the other hand, Mori reported a Pd(II)-catalyzed
pathway for the reaction between organoboron reagents and
by utilizing arylstannanes via Pd(II) catalysis in the presence
5
of oxygen or Cu(II) oxidants. However, these organometallic
2
alkenes in the presence of Cu(OAc) as an oxidant, which
involved transmetalation as the initial step in the catalytic
cycle. However, the reaction conditions remained harsh
(
1) For reviews, see: (a) Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV.
1
0
2
1
1
1
000, 100, 3009. (b) Ikeda, M.; El Bialy, S. A. A.; Yakura, T. Heterocycles
999, 51, 1957. (c) Shibasaki, M.; Boden, C. O. J.; Kojima, A. Tetrahedron
997, 53, 7371. (d) Gibson, S. E.; Middleton, R. J. Contemp. Org. Synth.
996, 3, 447. (e) Negishi, E.; Coperet, C.; Ma, S.; Liou, S.-Y.; Liu, F.
Chem. ReV. 1996, 96, 365. (f) de Meijere, A.; Meyer, F. E. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 2379. (g) Heck, R. F. Org. React. 1982, 27, 345.
(
100 °C, DMF) and excess Cu(II) reagent was utilized as an
1
1
oxidant, generating a poisonous waste.
(6) For toxicology studies, see: (a) Smith, P. J. Toxicological Data on
Organotin Compounds; Publication 538; International Tin Research Insti-
tute: London, 1978. (b) Chau, Y. K.; Wong, P. T. S. Some EnVironmental
Aspects of Organo-arsenic, Lead and Tin; NBS Special Publication (United
States), 1981, 618, 65-80. (c) Sandhu, G. K. J. Chem. Sci. 1983, 9, 36. (d)
Barnes, J. M.; Magos, L. Organomet. Chem. ReV. 1968, 3 (2), 137.
(7) Pyrene, M.; Quintard, J.-P.; Rahm, A. Tin in Organic Synthesis;
Butterworth: Boston, 1987; pp 36-37.
(8) Ullmann’s Encyclopedia of Industrial Chemistry, 6th ed., June 2001
Electronic Release; Wiley-VCH: Weinheim, Germany, 2001.
(9) Cho, C. S.; Uemura, S. J. Organomet. Chem. 1994, 465, 85.
(10) Du, X.; Suguro, M.; Hirabayashi, K.; Mori, A. Org. Lett. 2001, 21,
3313.
(
h) Heck, R. F. Acc. Chem. Res. 1979, 12, 146.
(2) (a) Hirabayashi, K.; Nishihara, Y.; Mori, A.; Hiyama, T. Tetrahedron
Lett. 1998, 39, 7893. (b) Hirabayashi, K.; Kondo, T.; Toriyama, F.;
Nishihara, Y.; Mori, A. Bull. Chem. Soc. Jpn. 2000, 73, 749. (c) Hirabayashi,
K.; Ando, J.; Kawashima, J.; Nishihara, Y.; Mori, A.; Hiyama, T. Bull.
Chem. Soc. Jpn. 2000, 73, 1409.
(
3) Motoba, K.; Motofusa, S.; Cho, C. S.; Uemura, S. J. Organomet.
Chem. 1999, 574, 3.
4) (a) Oda, H.; Morishita, M.; Fugami, K.; Sano, H.; Kosugi, M. Chem.
Lett. 1996, 811. (b) Fugami, K.; Hagiwara, S.; Oda, H.; Kosugi, M. Synlett
998, 477. (c) Hirabayashi, K.; Ando, J.; Nishihara, Y.; Mori, A.; Hiyama,
(
1
T. Synlett 1999, 99. (d) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518. (e)
Heck, R. F. J. Am. Chem. Soc. 1969, 91, 6707.
(11) For toxicology studies, see; (a) Beritic, T.; Dimov, D. ArhiV Za
Higijenu Rada I Toksikologiju 1970, 21 (3), 285. (b) Grebennikov, E. P.
SoVetskaia Meditsina 1969, 32 (4), 94.
(5) Parrish, J. P.; Jung, Y. C.; Shin, S. I.; Jung, K. W. J. Org. Chem.
2
002, 67, 7127.
1
0.1021/ol034458s CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/30/2003

The use of molecular oxygen as a sole reoxidant has been
reported in palladium-catalyzed methodologies, encompass-
that molecular oxygen played a pivotal role in Pd(II)-
catalyzed reaction through the reoxidation of Pd(0) species
12
ing oxidation of alcohols to carbonyl compounds, cycliza-
to Pd(II). Under these aerobic conditions, Na
to be the best, and several bases such as NaOAc, Cs
and K CO were effective as well. DMF was the choice of
2
CO
3
proved
13
tion of olefinic compounds, and synthesis of hydrogen
2 3
CO ,
1
4
15
peroxide. Recently, arylzinc compounds, triarylbismuth-
2
3
16
17
ines, and arylboronic acids were reported to be dimerized
in the presence of oxygen. Our group has also reported the
use of oxygen for the oxidative homocouplings of aryl and
akenylboronic acids.18 The mechanistic aspect of aerobic
oxidation of palladium catalysts via peroxopalladium(II)
species has been well rationalized by Stahl.1
the solvent, whereas protic solvents, including water and
EtOH, delivered biaryls via homocoupling reaction exclu-
1
7
sively. Regarding temperature, optimal results were ob-
tained at 50 °C, while longer reaction times (12-24 h) were
required to complete the reactions at 23 °C; increased
amounts of homocoupling products were produced at higher
temperatures such as 100 °C. When arylboronic acids were
utilized as coupling partners, phenols were sometimes
observed as minor side products along with the aforemen-
9
Described herein is the use of molecular oxygen as the
catalyst oxidant in Pd(II)-catalyzed couplings of organoboron
compounds and olefins. The presence of oxygen was critical
5,18
17c
for catalyst reoxidation as we reported earlier. As shown
in Table 1, a low yield of the product was obtained when
tioned biaryls.
To examine substrate versatility, we first probed the effect
of electron density on olefins as shown in Table 2. tert-Butyl
Table 1. Effect of Oxygen
Table 2. Effect of Electron Density on Olefins
entry
Pd catalysta
oxidant
yield
entry
R
yield
E/ Z ratio
1
2
3
4
5
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
noneb
air
O2
O2
noneb
12%
44%
87%
85%
0%
t
1
2
3
4
CO2 Bu (1)
87%
73%a
90%
86%
(E)-only
2/1
(E)-only
(E)-only
OBu
Ph
(4)
(5)
CH2Ph (6)
an-Butyl vinyl ether (2.0 equiv), 23 °C, 10 h. Yields were calculated on
the basis of boronic acid.
a
Amount used ) 10 mol%. b N2 condition.
the reaction was run under a nitrogen condition (entry 1).
Under air and oxygen, the product was obtained in 44 and
acrylate (1), which is an electron-poor alkene, was converted
smoothly to tert-butyl trans-cinnamate in 87% yield (entry
87% yields, respectively (entries 2 and 3). In a further study,
1). An electron-rich alkene, n-butyl vinyl ether (4) delivered
it was found that Pd(OAc) was the choice of the catalyst
2
7
3% of â-butoxystyrene with an isomeric ratio of 2/1 at 23
and that Pd(0) catalyst was also effective in delivering the
desired product in 85% yield in the presence of oxygen (entry
°
C after 10 h (entry 2). Styrene (5), an aromatic nonallylic
alkene, reacted with phenylboronic acid to give 90% of trans-
stilbene (entry 3). Allylbenzene (6) was converted to (E)-
4), whereas no product was observed under nitrogen condi-
tions (entry 5). Comparable results were obtained when 5
1
,3-diphenylpropene smoothly in 86% yield (entry 4). This
20
2
mol% Pd(OAc) was used. From these results, we inferred
newly developed protocol was effective regardless of the
electron density on olefins and was regioselective to provide
an (E)-isomer exclusively except with an electron-rich alkene.
After screening olefins, we investigated the scope and
limitation of organoboron compounds as summarized in
Table 3. 4-Methoxyphenylboronic acid (7), which has an
electron-donating group, and 3-acetylphenylboronic acid (8),
which has an electron-withdrawing group, showed similar
reactivities, furnishing the desired arylated products in 79
(
12) (a) Steinhoff, B. A.; Fix, S. R.; Stahl, S. S. J. Am. Chem. Soc. 2002,
1
2
6
24, 766. (b) Brink, G. T.; Arends, I. W. C. E.; Sheldon, R. A. Science
000, 287, 1636. (c) Peterson, K. P.; Larock, R. C. J. Org. Chem. 1998,
3, 3185.
(13) (a) Rohn, M.; Backvall, J.; Andersson, P. G. Tetrahedron Lett. 1995,
3
6, 7749. (b) Larock, R. C.; Hightower, T. R.; Hasvold, L. A.; Peterson,
K. P. J. Org. Chem. 1996, 61, 3584.
14) (a) Bianchi, D.; Bortolo, R.; D’Aloisio, R.; Ricci, M. Angew. Chem.,
Int. Ed. 1999, 38, 706. (b) Thiel, W. R. Angew. Chem., Int. Ed. 1999, 38,
157.
15) Hossain, K. M.; Kameyama, T.; Shibata, T.; Tagaki, K. Bull. Chem.
Soc. Jpn. 2001, 74, 2415.
16) Ohe, T.; Tanaka, T.; Kuroda, M.; Cho, C. S.; Ohe, K.; Uemura, S.
Bull. Chem. Soc. Jpn. 1999, 72, 1851.
17) (a) Smith, K. A.; Campi, E. M.; Jackson, W. R.; Marcuccio, S.;
(
3
(
(
(20) Reaction conditions: O2, Pd(OAc)2, Na2CO3, DMF, 50 °C, 3 h.
(
Naeslund, C. G. M.; Deacon, G. B. Synlett 1997, 131. (b) Wong, M. S.;
Zhang, X. L. Tetrahedron Lett. 2001, 42, 4087. (c) Yoshida, H.; Yamaryo,
Y.; Ohshita, J.; Kunai. A. Tetrahedron Lett. 2003, 44, 1541.
(
18) Parrish, J. P.; Jung, Y. C.; Floyd. R. J.; Jung, K. W. Tetrahedron
Lett. 2002, 43, 7899.
19) (a) Stahl, S. S.; Thorman, J. L.; Nelson, R. C.; Kozee, M. A. J. Am.
(
Chem. Soc. 2001, 123, 7188. (b) Stahl, S. S.; Thorman, J. L.; de Silva, N.;
Guzei, I. A.; Clark, R. W. J. Am. Chem. Soc. 2003, 125, 12.
2232
Org. Lett., Vol. 5, No. 13, 2003

Table 3. Various Aryl Boronic Acids Coupled with tert-Butyl
Table 4. Various Aryl Boron Reagents Coupled with
Acrylate
Allylbenzene
entry
ArB(OR)2
yield
1
2
3
4
5
7
8
11
12
13
80% (1/1.0)a
86% (1/1.6)a
83% (1/1.3)
85% (1/5.4)
82% (1/3.0)a
a
Reaction solvent ) CH3CN.
mixture of the double-bond-migrated isomers. Electron
density in arylboronic acids did not have a significant
influence on the results, still giving the desired products in
high yields (entries 1 and 2). Arylboronates containing bulky
fused aromatic or heterocyclic groups were equally effective
in this protocol to provide the regioisomeric mixtures (entries
3
-5).
Having obtained satisfactory results with monosubstituted
alkenes, we then turned our attention to the arylation of a
highly substituted system as depicted in Table 5. Ethyl trans-
and 78% yields, respectively. Indole derivatization on the
C-3 position was also possible by coupling 1-(phenylsul-
fonyl)-3-indoleboronic acid (9) with alkene 1 in good yield.
We found that arylboronates functioned as benign coupling
partners for this methodology, decreasing the formation of
Table 5. Coupling with Highly Substituted Olefins
1
7
21
side products such as biaryls and phenols. 2,2-Dimethyl-
,3-propanediol benzeneboronate (10) was prepared from the
1
22
corresponding arylboronic acids and subjected to the Pd(II)
catalysis, giving rise to the exclusive synthesis of tert-butyl
trans-cinnamate. Likewise, 3,5-dimethyl-4-methoxybenzene
catechol boronate (11) furnished the corresponding arylated
product in 79% yield. No biphenyl product was observed at
all. We were also interested in the reaction of fused aromatic
and heterocyclic boronic acids. The arylboronates of 1-naph-
thaleneboronic acid (12) and 4-dibenzofuranboronic acid (13)
afforded 85 and 77% yields of the desired arylated products,
respectively. Next, the coupling with 2,2-dimethyl-1,3-
propanediol boronate of thianaphthene-2-boronic acid (14)
was smooth with moderate yield.
Table 4 shows the reactions of allylbenzene (6) with
various boron compounds. Various arylboron compounds
were coupled with allylbenzene smoothly to deliver the
a 3-Acetylphenylboronic acid was used as a coupling partner.
crotonate (15) reacted with phenylboronic acid to give 70%
yield of ethyl â-methylcinnamate with exclusive (E)-con-
figuration (entry 1). trans-â-Methylstyrene (16) reacted
smoothly with both phenylboronic acid and 3-acetylphenyl-
boronic acid to furnish the corresponding trans-R-methyl-
stilbenes in high yields (entries 2 and 3). Conversely,
R-methylstyrene (17) delivered an inseparable mixture of
trans-R-methylstilbene and R-benzylstyrene in 69% yield in
a ratio of 1/1.5 (entry 4). Cyclohexene (18), a cyclic
disubstituted olefin, was also effective in our protocol to fur-
nish a 1/2 mixture of 3-phenylcyclohexene and 4-phenyl-
(
21) Reaction conditions : O2, 10 mol % Pd(OAc)2, Na2CO3, DMF, 50
°
C, 3 h.
(22) Shi, B.; Boyle, R. W. J. Chem. Soc., Perkin Trans. 1 2002, 11,
1
397.
Org. Lett., Vol. 5, No. 13, 2003
2233

cyclohexene in 48% yield (entry 5). These data implied that
this oxygen protocol could be applicable to most highly
substituted olefin systems, resulting in outstanding (E)-
selectivity.
To elucidate the catalytic pathway of this oxygen protocol,
we conducted the competition reactions using tert-butyl
23
acrylate (1, 3 mmol), 2,2-dimethyl-1,3-propanediol boronate
of 3-acetylphenylboronic acid (24, 1 mmol), and 2-iodo-
anisole (25, 1 mmol). As shown in Scheme 1, 71% of Pd(II)
Scheme 1. Competition Reaction
Figure 1. Reaction cycle.
to produce the desired product and Pd(0) species. Molecular
oxygen then oxidizes the Pd(0) to Pd(II) species, possibly
1
9
via a peroxopalladium(II) complex. The high efficiency of
the Pd(0) complex, Pd (dba) , can be explained by this
2
3
scheme involving the oxidation step of Pd(0) species by
oxygen. The preference of our oxygen-promoted Pd(II)
catalysis to the conventional Heck or Suzuki catalysis under
an oxygen atmosphere can also be explained by this reaction
scheme involving rapid oxidation of Pd(0) species. Therefore,
Pd(0)-catalyzed oxidative addition of 2-iodoanisole can be
suppressed to follow Heck or Suzuki pathways (cycle II).
In summary, we elaborated a mild and efficient Pd(II)
catalysis, an organometallic variation of Heck reaction. Our
newly developed protocol uses an environmentally friendly
and inexpensive oxidant, molecular oxygen, and provides
various aryl-alkenyl coupling products from a broad spec-
trum of olefins and arylboron compounds in good to excellent
yields. This oxygen protocol demonstrates a new mechanistic
concept that oxygen would promote the Pd(II) catalytic
pathway and in turn suppress the competing Pd(0) catalysis
encompassing Heck or Suzuki couplings.
a
1
b
2
c
Ar ) 3-acetylphenyl. Ar ) 2-methoxyphenyl. Pd(OAc)
2
(20
, DMF, 50 °C, 6 h. Oxygen was delivered by
bubbling into the reaction solution slowly.
d
2 3
mol%), Na CO
catalysis product 26 and 26% of Heck coupling product 27
were isolated using oxygen conditions, while only 18% of
6 was isolated together with Heck product as the major
product using oxygen free conditions (argon atmosphere).
The Suzuki coupling product 28 was detected in low yield
under both conditions. The side products,1 29 and 30, were
detected with oxygen conditions in 5 and 6% yields,
respectively. From these results, we inferred that molecular
oxygen promoted the desired Pd(II) catalysis and suppressed
the competing Pd(0) catalytic pathways.
2
24
7,21
Although the details are not yet known, we propose a
mechanistic catalytic cycle as shown in Figure 1. Presumably,
the Pd(II) works as the active species throughout the reaction
as suggested by Mori. As delineated in cycle I, transmeta-
lation of arylboronic acid gives Ar-Pd-L, and migratory
insertion of the olefin is followed by â-hydride elimination
Acknowledgment. We acknowledge generous financial
support in part from the National Institutes of Health (RO1
GM 62767). We also thank Dr. Anthony Piscopio at Array
BioPharma, Inc., for his helpful discussion.
10
Supporting Information Available: Representative ex-
perimental procedure and copies of the spectral data for the
representative products in schemes and tables are provided.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(23) Suzuki coupling product was detected in low yield from boron
reagent and halide; thus, excess alkene was used to maximize the efficiency
of the other reactions.
(24) In a separate Suzuki coupling reaction between 24 and 25, the
desired product 28 was isolated in 31% yield under oxygen and 71% yield
under argon conditions (20 mol % Pd(OAc)2, Na2CO3, DMF, 50 °C, 6 h).
OL034458S
2234
Org. Lett., Vol. 5, No. 13, 2003