Oxygen-promoted palladium(II) catalysis: Facile C(sp2)-C(sp 2) bond formation via cross-coupling of alkenylboronic compounds and olefins

Article abstract of DOI:10.1021/ol0483192

(Chemical Equation Presented) Oxygen-promoted Pd(II) catalysis facilitated the synthesis of conjugated dienes by cross-coupling of alkenylboronic compounds and various olefins including highly substituted alkenes and cyclohexenone. Under mild conditions, these versatile reactions were efficient and highly stereoselective.

Full text of DOI:10.1021/ol0483192

ORGANIC
LETTERS
2004
Vol. 6, No. 22
4037-4039
Oxygen-Promoted Palladium(II)
Catalysis: Facile C(sp2) C(sp2) Bond
−
Formation via Cross-Coupling of
Alkenylboronic Compounds and Olefins
Cheol Hwan Yoon, Kyung Soo Yoo, Sung Wook Yi, Rajesh K. Mishra, and
Kyung Woon Jung*
Department of Chemistry, UniVersity of South Florida (SCA 400),
4202 East Fowler AVenue, Tampa, Florida 33620
kjung@chuma.cas.usf.edu
Received August 23, 2004
ABSTRACT
Oxygen-promoted Pd(II) catalysis facilitated the synthesis of conjugated dienes by cross-coupling of alkenylboronic compounds and various
olefins including highly substituted alkenes and cyclohexenone. Under mild conditions, these versatile reactions were efficient and highly
stereoselective.
In recent years, significant advances have been made in the
molecular oxygen-promoted palladium catalysis for the use
of oxidation of alcohols to carbonyl compounds.1 However,
there have been only a few reports on carbon-carbon bond
formation,2,3 and they have failed to offer a general synthetic
method presumably due to poor understanding of the
catalysis. We have pioneered novel C-C bond formation
methods utilizing oxidative palladium catalysis to culminate
in communications on the homocoupling protocol4 and the
first report on a cross-coupling method.5
Suzuki-Miyaura6 and Stille reactions7 have been utilized
for the cross-coupling of alkenyl-alkenyl moieties to gener-
ate conjugated dienes. However, these reactions can be
cumbersome since both coupling substrates should be ste-
reoselectively prepared prior to coupling. The Heck reaction8-10
(1) (a) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400. (b) Steinhoff,
B. A.; Fix, S. R.; Stahl, S. S. J. Am. Chem. Soc. 2002, 124, 766. (c) Stahl,
S. S.; Thorman, J. L.; Nelson, R. C.; Kozee, M. A. J. Am. Chem. Soc.
2001, 123, 7188. (d) Ferreira, E. M.; Stoltz, B. M. J. Am. Chem. Soc. 2001,
123, 7725. (e) Jensen, D. R.; Pugsley, J. S.; Sigman, M. S. J. Am. Chem.
Soc. 2001, 123, 7475. (f) Brink, G. T.; Arends, I. W. C. E.; Sheldon, R. A.
Science 2000, 287, 1636. (g) Peterson, K. P.; Larock, R. C. J. Org. Chem.
1998, 63, 3185.
(2) For oxygen-promoted Pd-catalyzed homocoupling reactions, see: (a)
Yoshida, H.; Yamaryo, Y.; Ohshita, J.; Kunai, A. Tetrahedron Lett. 2003,
44, 1541. (b) Mukhopadhyay, S.; Rothenberg, G.; Lando, G.; Agbaria, K.;
Kazanci, M.; Sasson, Y. AdV. Synth. Catal. 2001, 343, 455. (c) Hossain,
K. M.; Kameyama, T.; Shibata, T.; Tagaki, K. Bull. Chem. Soc. Jpn. 2001,
74, 2415. (d) Wong, M. S.; Zhang, X. L. Tetrahedron Lett. 2001, 42, 4087.
(e) Ohe, T.; Tanaka, T.; Kuroda, M.; Cho, C. S.; Uemura, S. Bull. Chem.
Soc. Jpn. 1999, 72, 1851. (f) Smith, K. A.; Campi, E. M.; Jackson, W. R.;
Marcuccio, S.; Maeslund, C. G. M.; Deacon, G. B. Synlett 1997, 131.
(3) For oxygen-promoted Pd-catalyzed cross-coupling reactions, see: (a)
Andappan, M. M. S.; Nilsson, P.; Larhed, M. Chem. Commun. 2004, 218.
(b) Zou, G.; Zhu, J.; Tang, J. Tetrahedron Lett. 2003, 44, 8709. (c) Dams,
M.; De Vos, D. E.; Celen, S.; Jacobs, P. A. Angew. Chem., Int. Ed. 2003,
42, 3512. (d) Matoba, K.; Motofusa, S.-I.; Cho, C. S.; Ohe, K.; Uemura, S.
J. Organomet. Chem. 1999, 574, 3. (e) For Pd-catalyzed cross-coupling
reactions with Cu(II) as an oxidant: Du, X.; Suguro, M.; Hirabayashi, K.;
Mori, A. Org. Lett. 2001, 3, 3313.
(4) (a) Parrish, J. P.; Jung, Y. C.; Floyd, R. J.; Jung, K. W. Tetrahedron
Lett. 2002, 43, 7899. (b) Parrish, J. P.; Flanders, V. L.; Floyd, R. J.; Jung,
K. W. Tetrahedron Lett. 2001, 42, 7729.
(5) (a) Jung, Y. C.; Mishra, R. K.; Yoon, C. H.; Jung, K. W. Org. Lett.
2003, 5, 2231. (b) Parrish, J. P.; Jung, Y. C.; Shin, S. I.; Jung, K. W. J.
Org. Chem. 2002, 67, 7127. For an application, see: (c) Furman, B.;
Dziedzic, M. Tetrahedron Lett. 2003, 44, 8249.
(6) For reviews of the Suzuki-Miyaura reaction, see: (a) Miyaura, N.
Top. Curr. Chem. 2002, 219, 11. (b) Suzuki, A. J. Organomet. Chem. 1999,
576, 147. (c) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
(7) For a review of the Stille reaction, see: Farina, V.; Krishnamurthy,
V.; Scott, W. J. Org. React. 1997, 50, 1-652.
(8) For reviews of the Heck reaction, see: (a) Heck, R. F. Org. React.
1982, 27, 345. (b) Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV. 2000,
100, 3009. (c) Whitcombe, N. J.; Hii, K. K.; Gibson, S. E. Tetrahedron
2001, 57, 7449. (d) Gu¨rtler, C.; Buchwald, S. L. Chem. Eur. J. 1999, 5,
3107. (e) Kondolff, I.; Doucet, H.; Santelli, M. Tetrahedron Lett. 2003,
44, 8487.
10.1021/ol0483192 CCC: $27.50
© 2004 American Chemical Society
Published on Web 10/01/2004

has been considered as the best alternative to avoid this
problem. Due to inefficiency, poor selectivities, and harsh
conditions, Heck coupling has been limited in use, especially
with substituted olefins. Recently, Fu9a and Hartwig9b
reported mild Heck conditions for the coupling of aryl halides
with olefins. However, the reaction conditions require
phosphine ligands and longer reaction times (20-77 h). In
this account, we report a new synthetic method to address
these shortcomings and offer a generally applicable protocol.
Just recently, we discovered a mild means of oxidative
palladium catalysis, effecting carbon-carbon bond formation
between alkenylboron compounds and various olefins.
Monosubstituted olefins were facile in coupling, and the
yields and stereoselectivities were generally high (Table 1).
B). It was envisioned that a low concentration of boronic
ester would decrease the probability of the reaction between
the boronic ester and the incipient alkenylpalladium inter-
mediate, resulting in avoidance of homocoupling. Condition
B averted homocoupling to offer higher yields and cleaner
products, allowing for easy purification while the one-pot
condition was convenient and pragmatic. The details of the
conditions will be discussed in a separate full account.
Due to low yields and stereoselectivity, substituted olefins
have been poor substrates for Heck reactions. Thus, the
remedy for this chronic problem can be highly valuable,
prompting us to probe the feasibility of oxygen-promoted
Pd(II) catalysis (Table 2). At ambient temperatures, ethyl
Table 2. Coupling of Boronic Ester 1 with Highly Substituted
Table 1. Coupling of Hexenyl Boronic Ester 1 with Various
Alkenes
Alkenes
entry
1
R
product
yielda (%)
t
CO2 Bu
2
A: 85
B: 90
A: 82
B: 92
A: 81b
B: 91
A: 85
2
3
4
Ph
3
CH2OBn
4
CN
5c
a A: one-pot condition with 10 mol% of Pd(OAc)2, 3 h. B: slow addition
protocol with 2 mol% of Pd(OAc)2, 6 h. b 2 mol% of Pd(OAc)2. c E/Z
1
ratio is 3:2, as determined by H NMR.
a Condition B. b Reaction temperature: 50 °C. c E/Z ratio was determined
by 1H NMR. d Internal/terminal alkene ratio was determined by 1H NMR.
The reactions with tert-butyl acrylate and styrene afforded
(E,E)-dienes 2 and 3, respectively (entries 1 and 2). Fur-
thermore, the reaction with unreactive allyl benzyl ether took
place, successfully delivering (E,E)-diene 4 (entry 3). For
comparison, we conducted the Heck reaction of trans-
iodohexene with allyl benzyl ether under Jeffery conditions,10
known as mild Heck reaction conditions, and confirmed that
this method failed to afford any coupling product.11 The
coupling reaction with acrylonitrile provided an isomeric
mixture of diene 5 in 85% yield (entry 4).12
Because homocoupling4 was expected as the major side
reaction, we employed two different conditions, where boron
compounds were added in the beginning (condition A) and
where slow addition of organoborons was utilized (condition
crotonate and tert-butyl methacrylate afforded the desired
(E,E)-dienes 6 and 7 in high yields (entries 1 and 2). In the
case of substituted styrenes, coupling proceeded smoothly
at 50 °C (entries 3 and 4). With trans-â-methylstyrene, the
mixture of (E,E)- and (E,Z)-dienes 8 and 9 was obtained in
an 8.8:1 ratio in 88% overall yield. The reaction with
R-methylstyrene furnished an inseparable mixture of 10 and
11 in 84% yield via two possible â-elimination pathways
during the reaction cycle.8b Similarly to the previous
examples, E-selectivity was high as expected.
Contrary to acyclic alkenes, Heck reactions of cyclohex-
enone with aryl halides afforded a mixture of Heck coupling
product and conjugate addition product via a palladium
enolate intermediate.13 Recently, Myers reported a clever
Heck-type arylation via decarboxylative palladation at high
temperature (>80 °C).14 According to these previous reports,
(9) (a) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989. (b)
Stambuli, J. P.; Stauffer, S. R.; Shaughnessy, K. H.; Hartwig, J. F. J. Am.
Chem. Soc. 2001, 123, 2677. (c) Berthiol, F.; Doucet, H.; Santelli, M. Synlett
2003, 841.
(10) (a) Jeffery, T. Tetrahedron Lett. 1993, 34, 1925. (b) Jeffery, T.
Tetrahedron Lett. 1985, 26, 2667. (c) Jeffery, T. J. Chem. Soc., Chem.
Commun. 1984, 1247.
(12) In most cases, the Heck reaction of acrylonitrile afforded E- and
Z-coupling isomers as a result of a small difference in the two transition
states for concerted Pd-H syn-elimination of the migratory insertion
intermediate due to its smaller size. See: (a) ref 8b. (b) Crisp, G. T.; Glink,
P. T. Tetrahedron 1994, 50, 2623. (c) Kim, J.-I.; Patel, B. A.; Heck, R. F.
J. Org. Chem. 1981, 46, 1067.
(11)
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Org. Lett., Vol. 6, No. 22, 2004

Heck-type catalysis is challenging with cyclohexenone, and
there is no successful case of alkenylation to the best of our
knowledge. However, our protocol delivered the vinylated
product 12 in 76% yield without the concomitant formation
of the conjugate addition product (entry 5). The mildness of
our oxidative catalysis is presumed to be responsible for its
success, most likely through an alternate mechanism, which
will be the target of a separate investigation in the future.
To further examine the scope and limitation of this method,
we conducted coupling reactions between various alkenyl-
boron compounds and tert-butyl acrylate (Table 3). Under
1). These results implied retention of the geometry in
alkenylboron compounds during the catalytic process. Pina-
colboronic ester 1516 afforded (E,E)-diene 16 exclusively,
whereas the corresponding boronic acid 17 gave 80-85%
of 16 along with the homocoupling compound (entries 2 and
3). This finding indicated that alkenylboronic acids were less
resistant to homocoupling as compared to the corresponding
esters. Nonetheless, both boronic acids and esters were well-
suited for oxidative Pd(II) catalysis in most cases.
In addition, highly substituted alkenylboron compounds
were compatible with this method. Reaction of sterically
hindered 1-methylvinyl pinacolboronic ester (18)17 took place
efficiently to provide 19 exclusively and stereoselectively
(entry 4). The boronic esters 20 and 22 containing alcohol
functionalities also successfully gave rise to the correspond-
ing (E,E)-dienes 21 and 23 in high yields (entries 5 and 6).
Therefore, such highly functionalized boron compounds can
be used for the introduction of versatile functional groups
to the alkene compounds for further manipulation.
Table 3. Coupling of Various Alkenylboron Compounds
In conclusion, oxidative palladium(II) catalysis of vinyl
boron compounds with various alkenes provided the corre-
sponding conjugated dienes in good to excellent yields under
mild reaction conditions. Furthermore, expensive ligands and
additives are unnecessary, while oxygen finds utility as an
environmentally benign, economical reoxidant of the pal-
ladium catalyst. Additionally, high stereoselectivity as well
as functional group tolerance are worthy of note. This new
protocol is advantageous over the conventional and modified
Heck conditions and allows a wide array of substrates,
otherwise found difficult or impossible to react smoothly.
Due to its easy and convenient nature, this protocol is highly
practical, holding great promise for wide use. Mechanistic
insight and applications will be reported in due course.
Acknowledgment. We acknowledge generous financial
support from the National Institute of General Medical
Sciences of the National Institutes of Health (RO1 GM
71495).
a A: one-pot condition with 10 mol% of Pd(OAc)2, 3 h. B: slow addition
protocol with 2 mol% of Pd(OAc)2, 6 h. b TMS group was deprotected
during column chromatography.
Supporting Information Available: Representative ex-
perimental procedures with spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org.
both developed conditions, cis-hexenyl pinacolboronic ester15
led to the stereoselective formation of (E,Z)-diene 14 (entry
OL0483192
(13) (a) Costa, A.; Najera, C.; Sansano, J. M. J. Org. Chem. 2002, 67,
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