Communications
and hexane (1:99 to 10:90) as the eluent. The identity and purity of the
product was confirmed by 1H and 13C NMR spectroscopic, mass-
spectrometric, high-resolution mass-spectrometric, and elemental
analysis.
lectively with electron-rich olefins. For example, the vinyl
ether 1a was smoothly arylated by activated chlorides
[Eq. (4)], thus furnishing the corresponding ketones in high
Received: March 1, 2006
Published online: May 23, 2006
Keywords: Heck reaction · homogeneous catalysis ·
.
hydrogen bonding · ionic liquids · regioselectivity
[1] Recent reviews: a) M. Shibasaki, E. M. Vogl, T. Ohshima, Adv.
Synth. Catal. 2004, 346, 1533; b) R. B. Bedford, C. S. J. Cazin, D.
Holder, Coord. Chem. Rev. 2004, 248, 2283; c) S. Bräse, A. de
Meijere in Metal-Catalyzed Cross-Coupling Reactions, Vol. 1
(Eds.: A. de Meijere, F. Diederich), Wiley-VCH, Weinheim,
2004, p. 217; d) M. Larhed, A. Hallberg in Handbook of
Organopalladium Chemistry for Organic Synthesis, Vol. 1 (Ed.:
E.-I Negishi), Wiley-Interscience, NewYork, 2002, p. 1133;
e) A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114, 4350; Angew.
Chem. Int. Ed. 2002, 41, 4176; f) I. P. Beletakaya, A. V.
Cheprakov, Chem. Rev. 2000, 100, 3009.
yields. However, these reactions necessitated harsher con-
ditions and failed with deactivated chlorides under the
conditions employed.
In conclusion, we have demonstrated that ammonium
salts that can act as hydrogen-bond donors exert a remarkable
accelerating effect on the rates of the regioselective arylation
of electron-rich olefins by aryl halides in ionic liquids and
common solvents. More than two decades ago, tetraalkylam-
monium salts, such as [NBu4][Cl], were discovered to accel-
erate the Heck reaction.[16] The Jeffery conditions can be
successfully employed for palladium catalysts containing
monodentate phosphines or no ligands. Under such condi-
tions, the Heck reaction presumably proceeds by the neutral
pathway,[3] which involves anion-ligated palladium species, as
indicated by the extensive studies of Amatore and Jutand.[17]
In contrast, the Pd–dppp catalysis described herein is typical
of the Heck reaction proceeding by the cationic pathway,[3,4]
[2] Commercial applications: a) A. Zapf, M. Beller, Top. Catal.
2002, 19, 101; b) J. G. de Vries, Can. J. Chem. 2001, 79, 1086;
c) A. Eisenstadt, D. J. Ager in Fine Chemicalsthrough Hetero-
geneousCatalysis (Eds.: R. A. Sheldon, H. van Bekkum), Wiley-
VCH, Weinheim, 1998, p. 576.
[3] W. Cabri, I. Candiani, Acc. Chem. Res. 1995, 28, 2.
[4] Examples of mechanistic studies: a) R. J. Deeth, A. Smith, J. M.
Brown, J. Am. Chem. Soc. 2004, 126, 7144; b) H. von Schenck, B.
Akermark, M. Svensson, J. Am. Chem. Soc. 2003, 125, 3503;
c) H. von Schenck, B. Akermark, M. Svensson, Organometallics
2002, 21, 2248.
[5] Recent examples of regioselective arylation: a) A. L. Hansen, T.
Skrydstrup, J. Org. Chem. 2005, 70, 5997; b) K. S. A. Vallin, Q.
Zhang, M. Larhed, D. P. Curran, A. Hallberg, J. Org. Chem.
2003, 68, 6639; c) P. Nilsson, M. Larhed, A. Hallberg, J. Am.
Chem. Soc. 2001, 123, 8217; d) M. Larhed, A. Hallberg, J. Org.
Chem. 1997, 62, 7858; e) W. Cabri, I. Canadiniani, A. Bedeschi,
R. Santi, J. Org. Chem. 1993, 58, 7421; f) W. Cabri, I.
Canadiniani, A. Bedeschi, S. Penco, R. Santi, J. Org. Chem.
1992, 57, 1481.
although the detailed mechanism of the rate acceleration by
+
]
[HnNR4Àn
(n = 1, 2) remains open for discussion, partic-
ularly with regard to the proposed effect of hydrogen bonding
on the equilibrium shown in Equation (2). To the best of our
knowledge, the chemistry presented represents the first
generic method to conduct the regioselective Heck reaction
of electron-rich olefins with aryl halides with no need for
silver or thallium-based halide scavengers.
[6] a) J. Mo, L. Xu, J. Xiao, J. Am. Chem. Soc. 2005, 127, 751; b) L.
Xu, W. Chen, J. Ross, J. Xiao, Org. Lett. 2001, 3, 295.
[7] The first examples of the Heck reaction in ionic liquids: D. E.
Kaufmann, M. Nouroozian, H. Henze, Synlett 1996, 1091.
[8] Recent examples of Heck coupling in ionic liquids: a) D. Zhao,
Z. Fei, T. Geldbach, R. Scopelliti, P. J. Dyson, J. Am. Chem. Soc.
2004, 126, 15876; b) J. Xiao, B. Twamley, J. M. Shreeve, Org.
Lett. 2004, 6, 3845; c) H. Hagiwara, Y. Sugawara, T. Hoshi, T.
Suzuki, Chem. Commun. 2005, 2942; d) C. C. Cassol, A. P.
Umpierre, G. Machado, S. I. Wolke, J. Dupont, J. Am. Chem.
Soc. 2005, 127, 3298; e) V. Calo, A. Nacci, A. Monopoli, E. Ieva,
N. Cioffi, Org. Lett. 2005, 7, 617.
[9] Recent reviews on ionic liquids: a) N. Jain, A. Kumar, S.
Chauhan, S. M. S. Chauhan, Tetrahedron 2005, 61, 1015; b) T.
Welton, Coord. Chem. Rev. 2004, 248, 2459; c) J. Dupont, R. F.
de Souza, P. A. Z. Suarez, Chem. Rev. 2002, 102, 3667; d) R.
Sheldon, Chem. Commun. 2001, 2399; e) P. Wassercheid, W.
Keim, Angew. Chem. 2000, 112, 3926; Angew. Chem. Int. Ed.
2000, 39, 3772.
Experimental Section
A typical procedure for the arylation of vinyl ether 1a: An oven-
dried, two-necked round-bottom flask containing a stir bar was
charged with an aryl halide
2 (1.0 mmol), Pd(OAc)2 (6 mg,
0.025 mmol), dppp (21 mg, 0.05 mmol), [HNEt3][BF4] (284 mg,
1.5 mmol), and [bmim][BF4] (2 mL) under nitrogen at room temper-
ature. Following degassing three times, 1a (204 mg, 2.0 mmol) and
HNiPr2 (153 mg, 1.5 mmol) were injected sequentially. The flask was
placed in an oil bath, and the reaction mixture was stirred and heated
at the desired temperature. After an appropriate reaction time, the
flask was removed from the oil bath and cooled to room temperature.
A small sample was then taken for NMR spectroscopic analysis. To
the rest of the mixture, aqueous HCl (5%, 5 mL) was added and
following stirring for 0.5 h, CH2Cl2 (20 mL) was added. After
separation of the CH2Cl2 phase, the aqueous layer was extracted
with CH2Cl2 (2 20 mL) and the combined organic layers were
washed with water until neutral, dried (Na2SO4), filtered, and
concentrated in vacuo. The aryl methyl ketone 4 was isolated by
flash chromatography on silica gel using a mixture of ethyl acetate
[10] A. F. Littke, G. C. Fu, J. Am. Chem. Soc. 2001, 123, 6989.
[11] A recent review: J. M. Llinares, D. Powell, K. Bowman-James,
Coord. Chem. Rev. 2003, 240, 57.
[12] Under the conditions of 1a (2.0 equiv), 2a (1.0 mmol), nBu4NBr
(1.5 equiv), Pd(OAc)2 (10 mol%), dppp (20 mol%), and Et3N
4156
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 4152 –4157