Palladium-catalyzed regioselective arylation of an electron-rich olefin by aryl halides in ionic liquids

Article abstract of DOI:10.1021/ol000362b

equation presented Palladium-catalyzed arylation of the electron-rich olefin butyl vinyl ether has been accomplished in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF₄]), using as the arylating agents aryl iodides and bromides instead of the commonly used, but commercially unavailable and expensive, aryl triflates. The reaction proceeds with high efficiency and remarkable regioselectivity, leading almost exclusively to substitution by various aryl groups at the olefinic carbon α to the heteroatom of butyl vinyl ether.

Full text of DOI:10.1021/ol000362b

ORGANIC
LETTERS
2001
Vol. 3, No. 2
295-297
Palladium-Catalyzed Regioselective
Arylation of an Electron-Rich Olefin by
Aryl Halides in Ionic Liquids
Lijin Xu, Weiping Chen, James Ross, and Jianliang Xiao*
LeVerhulme Centre for InnoVatiVe Catalysis, Department of Chemistry,
UniVersity of LiVerpool, LiVerpool L69 7ZD, U.K.
j.xiao@liV.ac.uk
Received November 27, 2000
ABSTRACT
Palladium-catalyzed arylation of the electron-rich olefin butyl vinyl ether has been accomplished in the ionic liquid 1-butyl-3-methylimidazolium
tetrafluoroborate ([bmim][BF4]), using as the arylating agents aryl iodides and bromides instead of the commonly used, but commercially
unavailable and expensive, aryl triflates. The reaction proceeds with high efficiency and remarkable regioselectivity, leading almost exclusively
to substitution by various aryl groups at the olefinic carbon r to the heteroatom of butyl vinyl ether.
Palladium-catalyzed arylation or vinylation of olefins by aryl
or vinyl halides, that is, the Heck reaction, has become one
of the most important tools in synthetic chemistry.1 The
reaction works impressively well with a wide range of
electron-deficient and unactivated olefins, affording high
selectivity to products resulting from arylation or vinylation
at the less substituted position of the olefinic double bond.
However, with electron-rich acyclic olefins such as enol
ethers and enamides, mixtures of regioisomers usually result
with standard Heck arylation conditions, thus limiting the
applicability of the Heck reaction in synthesis.1,2 Regio-
selective substitution at the olefinic carbon R to the hetero-
atoms of enol ethers or enamides is achievable when the
arylating halide is replaced by a triflate or when a stoichio-
metric quantity of silver triflate or thallium acetate is added.2
Thallium acetate appears to be preferred with aryl bromides
as arylating agents.2a The drawback of this approach is that
triflates are rarely commercially available and are far more
expensive to acquire than the halides, and large amounts of
inorganic salts are used and generated. We herein report that
palladium-catalyzed, highly regioselective arylation of the
electron-rich olefin butyl vinyl ether 1 by aryl halides 2 can
readily be accomplished in the ionic liquid 1-butyl-3-
methylimidazolium tetrafluoroborate ([bmim][BF4]),3 without
resorting, for the first time, to aryl triflates or silver and
thallium additives (Scheme 1).4
The palladium-phosphine-catalyzed Heck reaction is now
generally accepted to proceed via two pathways, one being
neutral, resulting in â arylation products such as 3, and the
(3) For recent reviews on reactions in ionic liquids, see: (a) Carlin, R.
T.; Wilkes, J. S. In AdVances in Nonaqueous Chemistry; Mamantov, G.,
Popov, A., Eds.; VCH: New York, 1994. (b) Chauvin, Y.; Olivier, H.
CHEMTECH 1995, 25, 26. (c) Seddon, K. R. J. Chem. Technol. Biotechnol.
1997, 68, 351. (d) Olivier, H. J. Mol. Catal. A: Chem. 1999, 146, 285. (e)
Welton, T. Chem. ReV. 1999, 99, 2071. (f) Wasserscheid, P.; Keim, W.
Angew. Chem., Int. Ed. 2000, 39, 3772.
(4) Regiocontrol is possible for the coupling of aryl halides and triflates
with heterosubstituted olefins that bear additional functionalities capable
of chelating to palladium: (a) Andersson, C.-M.; Larsson, J.; Hallberg, A.
J. Org. Chem. 1990, 55, 5757. (b) Badone, D.; Guzzi, U. Tetrahedron Lett.
1993, 34, 3603. (c) Larhed, M.; Andersson, C.-M.; Hallberg, A. Tetrahedron
1994, 50, 285. (d) Crisp, G. T.; Gebauer, M. G. Tetrahedron 1996, 52,
12465.
(1) For recent reviews, see: (a) Brase, S.; de Meijere, A. In Metal-
Catalyzed Cross-coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-
VCH: Weinheim, 1998. (b) Link, J. T.; Overman, L. E. In Metal-Catalyzed
Cross-coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998. (c) Crisp, G. T. Chem. Soc. ReV. 1998, 27, 427. (d)
Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009.
(2) (a) Cabri, W.; Candiani, I.; Bedeschi, A.; Penco, S. J. Org. Chem.
1992, 57, 1481. (b) Cabri, W.; Candiani, I.; Bedeschi, A. J. Org. Chem.
1993, 58, 7421. (c) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2.
(d) Larhed, M.; Hallberg, A. J. Org. Chem. 1997, 62, 7858.
10.1021/ol000362b CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/16/2000

Scheme 1
Table 1. Solvent Effect on the Heck Arylation of Butyl Vinyl
Ether 1 by 1-Bromonaphthalene 2a in Various Solventsa
solvent
convn, %b
R/âc
E/Zd
toluene
acetonitrile
DMF
DMSO
[bmim][BF4]
23
36
100
100
50
46/54
69/31
60/40
75/25
>99/1
68/32
75/25
77/23
79/21
a Reactions were run with 1.0 mmol of 1, 5 equiv of 2a, 1.2 equiv of
Et3N, 2.75 mol % of DPPP, and 2.5 mol % of Pd(OAc)2 at 100 °C for 18
h. The product was identified/analyzed by NMR, GC, and GC-MS and by
comparison with literature data and/or authentic samples.9 b Conversion
of 1 to 3 and 4. c Molar ratio of 4/3. When the product 3 could not be
detected by GC and NMR, a value of >99/1 was assigned. d Ratio of trans/
cis isomers of 3.
1).9 The results are given in Table 1. Among all these
solvents, the only one capable of effecting the regioselective
arylation of 1 was [bmim][BF4], as evidenced by the ratio
of R substituted 4 to â substituted 3 (R/â). In the four
molecular solvents with widely differing polarities,10 some
of which are commonly used in Heck reactions, none of the
reactions affords an R/â ratio close to that observed in the
ionic liquid. Of further interest is the observation that while
decomposition of palladium complexes to various degrees
into palladium black always accompanied the arylation in
the molecular solvents, palladium black was never observed
in the ionic liquid. Evidently, not only does [bmim][BF4]
promote the ionic pathway in the direct arylation of electron-
rich olefins by aryl halides to preferentially give the R
arylated product, it also plays a role in stabilizing the active
palladium-phosphine species involved in such reactions.
Table 1 also shows that the arylation by Pd(OAc)2 in the
presence of ca. 1 equiv of DPPP is slower in [bmim][BF4]
than in DMF and DMSO. The lower rates associated with
the ionic liquid could result from the phosphine ligand being
inadequate, some of which may be consumed in the reduction
of Pd(II) to Pd(0).1 The active catalyst involved in the
arylation is generally believed to be a Pd(0) species.1,2
Consistent with this interpretation, palladium without a
phosphine ligand displayed negligent activity in the arylation
reaction in [bmim][BF4], and addition of an additional 1
equiv of DPPP or replacement of Pd(OAc)2 by a Pd(0)
complex Pd2(dba)3 (dba ) dibenzylideneacetone) led to a
marked increase in the arylation rate. For example, the
conversion of 2e rose from 21 to 90% when the Pd(0)
precatalyst was employed to replace Pd(OAc)2 in the
coupling with 1.
other ionic, leading to R arylation products such as 4.1,2,5
The neutral route is characterized by phosphine dissociation
from palladium, whereas the ionic route proceeds by dis-
sociation of halide or triflats ions. Understandably, the ionic
pathway is favored by the use of aryl triflates and bidentate
phosphines.2,6 In continuing our study on catalysis in ionic
liquids,7 we wondered whether the compulsory use of a
triflate or addition of silver salts could be avoided when the
Heck arylation is carried out in an ionic liquid such as
[bmim][BF4]. Generation of the olefin-coordinated cationic
palladium species in the ionic pathway from a neutral
palladium-aryl halide complex and a neutral olefin could
be facilitated in an ionic environment provided by the ionic
liquids.8 In fact, earlier studies have already shown that the
reaction of [LPdArX] (L ) diphosphine, X ) halide) with
olefins can be greatly accelerated in a polar solvent via
stabilization of the ionic species generated.5b
To determine if direct, regioselective arylation of electron-
rich olefins by aryl halides could occur in ionic liquids
without using triflates or silver salts, we first examined the
arylation of 1 by 1-bromonaphthalene 2a in [bmim][BF4]
under conditions previously established for triflates in DMF,
where the active catalyst is derived in situ from Pd(OAc)2
and 1.1 equiv of 1,3-bis(diphenylphosphino)propane (DPPP).2a
For comparison, we also carried out the same reaction in
four molecular solvents: toluene, acetone, DMF, and DMSO.
A typical reaction consisted of simply heating a mixture of
1, 2a, Pd(OAc)2, and DPPP in a chosen solvent under an
atmosphere of argon. The R arylated product 4 was isolated
as the aryl methyl ketone 5 following acidification (Scheme
(9) The products from this study are known compounds. For their physical
and spectroscopic data, see: (a) Ichinose, N.; Mizuno, K.; Otsuji, Y.;
Caldwell, R.; Helms, A. M. J. Org. Chem. 1998, 63, 3176. (b) Kusama,
H.; Narasaka, K. Bull. Chem. Soc. Jpn. 1995, 68, 2379. (c) Hachiya, I.;
Moriwaki, M.; Kobayashi, S. Bull. Chem. Soc. Jpn. 1995, 68, 2053. (d)
Takagi, K.; Sasaki, K.; Sakakibara, Y. Bull. Chem. Soc. Jpn. 1991, 64,
1118. (e) Cabri, W.; Candiani, I.; Bedeschi, A.; Santi, R. J. Org. Chem.
1990, 55, 3564. (f) Pouchert, C. J. The Aldrich Library of NMR Spectra,
2nd ed.; Aldrich Chemical Co.: Milwaukee, 1983. (g) Buckingham, J.
Dictionary of Organic Compounds, 5th ed.; Chapman Hall: New York,
1982. (h) Reference 2b.
(5) (a) Ozawa, F.; Kubo, A.; Hayashi, T. J. Am. Chem. Soc. 1991, 113,
1417. (b) Portnoy, M.; Ben-David, Y.; Rousso, I.; Milstein, D. Organo-
metallics 1994, 13, 3465.
(6) In contrast to halide ions, triflate can easily dissociate from the ArPd-
(II)X species formed in the Heck reaction: (a) Jutand, A.; Mosleh, A.
Organometallics 1995, 14, 1810. (b) Brown, J. M.; Hii, K. K. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 657.
(7) (a) Chen, W.; Xu, L.; Chatterton, C.; Xiao, J. Chem. Commun. 1999,
1247. (b) Xu, L.; Chen, W.; Xiao, J. Organometallics 2000, 19, 1123.
(8) This is what one would expect on the basis of Hughes-Ingold
rules: Reichardt, C. SolVents and SolVent Effects in Organic Chemistry,
2nd ed; VCH: Weinheim, 1988.
(10) The dielectric constants, which can be used as a quantitative measure
of solvent polarity, of the four molecular solvents range from 2.4 to 46.5.
296
Org. Lett., Vol. 3, No. 2, 2001

On the basis of the above studies, the arylation of 1 in
[bmim][BF4] was undertaken for a variety of aryl halides in
the presence of Pd(OAc)2 and 2 equiv of DPPP. The results
obtained are summarized in Table 2. As shown in the table,
As may be expected, replacement of aryl halides with the
corresponding triflates gives faster rates in [bmim][BF4].
Thus, the arylation of 1 by phenyl triflate afforded a 100%
conversion within 2 h with an R/â > 99/1. In contrast, in
the case of 2h, the reaction was only 20% complete under
otherwise identical conditions. These observations seem to
indicate that the rate-determining step of the arylation of 1
by aryl halides 2 in [bmim][BF4] is the same as that proposed
for the normal Heck reaction involving deactivated aryl
halides, namely, oxidative addition of the aryl halides to a
Pd(0) species.1 In DMF with triflates as substrate, the rate-
controlling step has been proposed to be the migratory
insertion of olefins into Pd-Ar bonds.2a
It has been speculated for some time that the unique ionic
environment imposed by an ionic liquid on a chemical
reaction may change its course and so one could expect to
see a general “ionic liquid effect”.3 The results presented in
this paper demonstrate that there exists such an ionic liquid
effect, and this effect can be exploited for interesting but
traditionally formidable chemical syntheses. Until now, the
Heck arylation of electron-rich olefins by aryl halides has
been hampered by low regioselectivity, unless commercially
unavailable and expensive triflates or silver salts are used.
With the environmentally attractive ionic liquids such as
[bmim][BF4] as the reaction media, highly regioselective and
efficient arylation can now readily be achieved by directly
employing the easily accessible aryl halides. The key to the
success of the chemistry probably lies in the accelerating
effect of the ionic liquid on the ionic pathway of the Heck
reaction.
Table 2. Heck Arylation of Butyl Vinyl Ether 1 by Aryl
Halides 2a-j in [bmim][BF4]a
substrate temp, °C time, h convn, %
R/â
yield, %b
2a
2b
2c
2d
2e
2f
100
80
24
24
36
36
36
24
24
24
36
24
100
100
100
100
100
100
100
100
100
100
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
95
94
94
90
92
93
97c
95c
88
87
110
120
120
100
120
100
120
120
2g
2h
2i
2jd
a 2 equiv of DPPP. Other reaction conditions except temperature and
time were given in Table 1. b Isolated yield of 5. c Determined by NMR
and GC of the acidified mixture. d 5 mol % of Pd(OAc)2 was used.
excellent regioselectivity together with high isolated yields
for the aryl methyl ketones 5 was obtained in all the reactions
in the ionic liquid, regardless of the nature of the substituents
on the aromatic ring. Thus, with bromobenzenes bearing
either strongly electron withdrawing or electron donating
substituents such as -CN or -OMe, the R/â ratios remained
> 99/1, suggesting that the neutral pathway is either
completely suppressed or its involvement in the arylation is
insignificant compared with the ionic pathway in the ionic
liquid. Similar observations were made in DMF, that is, the
nature of the substituents of aryl triflates exerted no
significant effects on the R/â ratio.2a Under the conditions
given in Table 2, all the reactions went to completion.
However, since the reaction times were not optimized, shorter
times are possible for complete conversions. For example,
the coupling of bromobenzene 2h with 1 was complete within
a 20 h reaction time.
Acknowledgment. We are grateful to the University of
Liverpool Graduates Association (Hong Kong) and the
EPSRC for postdoctoral research fellowships (L.X. and
W.C.) and the EPSRC for a QUOTA studentship (J.R.).
Support from the industrial partners (Synetix, Johnson
Matthey, Catalytica, Air Products, and Syntroleum) of the
Leverhulme Centre for Innovative Catalysis is also gratefully
acknowledged.
OL000362B
Org. Lett., Vol. 3, No. 2, 2001
297