facilitating R-arylation (Scheme 1). However, a drawback of
this strategy is that triflates are base-sensitive and thermally
labile, and the inorganic additives create new problems, e.g.
waste salts, toxicity, and added cost. Recently, we found that
the ionic conditions could also be met by simply adopting ionic
liquid solvents.5,10 Specifically, we showed that electron-rich
olefins can be arylated highly regioselectively by aryl halides
TABLE 1. Screening Solvents for Regioselective Arylation of a
Vinyl Ether with Pd-mBDPPa
conversion
b
(%)c
R/âc
E/Zc
entry
solvent
ꢀr
5
in such solvents without recourse to any halide scavengers. It
1
2
3
4
5
6
7
[bmim][PF6]
DMSO
DMF
87
94
82
78
70
29
12
50
>99/1
>99/1
54/46
50/50
53/47
47/53
47/53
>99/1
is believed that the ionic medium promotes the formation of
the cationic palladium species and hence the branched product.
However, there is still a need to develop catalysts that work for
a wider range of substrates and function in a broader spectrum
of solvents.
46.45
36.71
37.78
35.94
2.21
84/16
82/18
75/25
80/20
77/23
DMAc
CH3CN
1,4-dioxane
toluene
2.38
46.45
d
As part of our ongoing research aimed at understanding and
controlling the regioselectivity of internal arylation of electron-
rich olefins, we have attempted to develop more efficient
palladium catalysts. A focal point was on new phosphine ligands
on the basis of the DPPP [1,3-bis(diphenylphosphino)propane]
backbone, as DPPP has proved to be the best ligand of choice
8
DMSO
a
Reaction conditions: 1a (1.0 mmol), 2 (2.0 mmol), Et3N (1.5 mmol),
b
Pd(OAc)2 (2 mol %), mBDPP (4 mol %), solvent (1.0 mL). Relative
permittivity taken from ref 15. c Determined by H NMR; a R/â-ratio of
1
d
>
99/1 was assigned when 4a was not detected. (R,R)-BDPP was used
instead of mBDPP.
2
,5,6c-i
for the R-arylation of electron-rich olefins.
In common
solvents, however, catalysis by Pd-DPPP generally affords a
87% conversion under the same reaction conditions (entry 1).
The regioselectivity of the reaction decreased dramatically in
other solvents, from DMF to toluene, giving rise to a mixture
of R- and â-arlyated products (entries 3-7). While the regio-
selectivity remained approximately the same for these solvents,
the reaction rate decreased as the polarity of the solvent
decreased. Interestingly, when mBDPP was replaced with its
chiral analogue, (R,R)-BDPP, a slower arylation resulted,
although the regioselectivity remained the same (entry 8 and
vide infra). The high R-regioselectivity in DMSO and [bmim]-
[PF6] is not a simple coincidence, as they both are capable of
promoting the formation of ionic palladium species. In the case
of DMSO, its high polarity and good capability in coordinating
mixture of regioisomers.3 Herein, we report that mBDPP
,5b
[meso-2,4-bis(diphenylphosphino)pentane] in combination with
palladium forms an effective catalyst that allows for regiose-
lective R-arylation with aryl bromides of electron-rich olefins
in DMSO with no need for an ionic liquid solvent nor for a
halide scavenger. It is noteworthy that mBDPP has not been
applied to the Heck reaction before, although it has been used
as an efficient ligand in copolymerization11 and hydrogenation.
Preliminary experiments were performed to examine the
effectiveness of the ligand in different solvents, including both
molecular solvents and ionic liquid. [bmim][PF6] was chosen
as a representative of the latter. Arylation of the benchmark
electron-rich olefin butyl vinyl ether (2) with 2-bromonaphtha-
lene (1a) was taken as a model reaction. The results are
presented in Table 1. As can be seen, among the molecular
solvents chosen, DMSO afforded the highest conversion with
an exclusive regioselectivity for the R-arylation product 3a (entry
12
1
3
to Pd(II) must at least partly account for this. Apart from our
recent investigation, which supports that ionic liquids enable
the ionic Heck pathway in the arylation of electron-rich olefins
5
by aryl halides, examples have been presented that demonstrate
that ionic liquids can stabilize unusual ionic reaction intermedi-
14
2
). A similar regioselectivity was observed in the ionic liquid
ates. The exclusive formation of the R-product in DMSO with
Pd-mBDPP represents one of the few examples of regioselec-
tive internal arylation in common solvents by aryl halides with
no use of a halide scavenger. Hallberg et al. have previously
reported similar regioselective arylation reactions in wet DMF,
with water acting as an indispensable additive for boosting
[bmim][PF6]. However this reaction was slower, affording a
(
8) (a) Bengtson, A.; Larhed, M.; Hallberg, A. J. Org. Chem. 2002, 67,
5
2
854. (b) Olofsson, K.; Sahlin, H.; Larhed, M.; Hallberg, A. J. Org. Chem.
001, 66, 544. (c) Vallin, K. S. A.; Larhed, M.; Johansson, K.; Hallberg,
A. J. Org. Chem. 2000, 65, 4537. (d) Olofsson, K.; Larhed, M.; Hallberg,
A. J. Org. Chem. 2000, 65, 7235. (e) Olofsson, K.; Larhed, M.; Hallberg,
A. J. Org. Chem. 1998, 63, 5076.
6
e
solvent polarity. More recently, we showed that 2 could be
regioselectively arylated by aryl bromides with Pd-DPPP
catalysis in DMSO in the presence of an ionic liquid.5c In neat
common organic solvents, Pd-DPPP generally gives rise to a
(
9) (a) Carfagna, C.; Musco, A.; Salllese, G.; Santi, R. J. Org. Chem.
1
991, 56, 261. (b) Grigg, R.; Loganathan, V.; Santhakumar, V.; Sridharan,
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2,5b
mixture of regioisomers as aforementioned. For instance, the
arylation of 2 by p-bromobenzaldehyde led to a R/â-ratio of
86/14 with Pd-DPPP in DMSO under similar conditions.5b
Encouraged by the results in DMSO, we extended this
chemistry to other aryl bromides. The arylarion of n-butyl vinyl
ether 2 (2.0 mmol) by a spectrum of aryl bromides 1 (1.0 mmol)
in the presence of Pd(OAc)2 (2-4 mol %) and mBDPP (4-8
1
1
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(
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468 J. Org. Chem., Vol. 71, No. 19, 2006