t
demanding IPr‚HCl (1) (IPr ) 1,3-bis(2,6-diisopropylphen-
yl)imidazol-2-ylidene) or IMes‚HCl (2) (IMes ) 1,3-bis-
effective additive for Pd
2
(dba)
3 3
/P Bu catalyzed Stille reac-
18
tion proved to be less effective (Table 1, entry 2). However,
(
2,4,6-trimethylphenyl)imidazol-2-ylidene) mediates the cou-
9
10
plings of aryl halides with amines, organomagnesium,
organoboron.11 and organosilicon reagents. On the basis
of these observations and the fact that organostannanes are
isoelectronic with organosilicon compounds, it was of interest
to examine whether this palladium/imidazolium salt system
12
Table 1. Effect of Base on Pd(OAc)
Cross-Coupling of 4-Chlorotoluene with Phenyl(trimethyl) Tin
2
/IPr‚HCl Catalyzed
a
could catalyze the Stille reaction. We now wish to report
n
the use of Pd(II)/IPr‚HCl and TBAF ( Bu
4
NF) as a base in
the cross-coupling reaction of aryl halides with organostan-
nane reagents.
It is well-known that, like silicon,13 tin is fluorophilic.14
Consequently, the resulting hypervalent organostannate spe-
cies generated in the reaction of the organostannane with
the fluoride anion are more labile with regard to the
entry
base
none
yield (%)b
1
2
3
4
5
6
7
<5
22
74c
30
7
15
16
CsF
CsF
transmetalation reaction. Kosugi et al. have reported that
Pd(dba) /PPh /TBAF does not catalyze the Stille coupling
2
3
t
KO Bu
of aryl chlorides. In an effort to overcome the limitations of
the Stille reaction, e.g., slow transmetalation step and removal
of tin byproducts, the use of hypervalent stannate species
was investigated.
Cs2CO3
TBAF
NaOH
54
32
a
Reaction conditions: 1.0 mmol of aryl chloride, 1.1 mmol of arylstan-
We have found that treatment of 1.1 equiv of Me
3
PhSn
nane, 2 mmol of TBAF, 3.0 mol % Pd(OAc) , 3.0 mol % IPr‚HCl, 1 mL
2
of dioxane, 100 °C. b GC yields. Yields are average of two runs. Pd(II)/
c
with 2 equiv of TBAF resulted in the formation of a
hypervalent fluorostannate anion (Scheme 2).17
2
IPr‚HCl ratio was used.
when a Pd/IPr‚HCl ratio of 1:2 was used, the reaction of
-chlorotoluene with Me PhSn led to a 74% yield of the
cross-coupling product (Table 1, entry 3). Attempts to
Scheme 2. Hypervalent Stannate Intermediate
4
3
1
9
couple other aryl halides using CsF as an additive/base were
t
unsuccessful. Other bases such as Cs
2
CO
3
, KO Bu, and
NaOH proved to be ineffective for the cross-coupling of
4
-chlorotoluene with PhSnMe
3
(Table 1, entries 4, 5, and
7
). The role of the TBAF additive (base) in these transforma-
-
20
tions is 3-fold: the strong base F
initially deprotonates
the imidazolium chloride to form the free carbene ligand in
situ, which coordinates to Pd. It also facilitates the trans-
metalation step by forming the more reactive hypervalent
tin species, and finally it helps the removal of tin byproducts
from the reaction mixture.
Investigation of other imidazolium salts as ligand precur-
sors led to the observation that the bulkier and less electron-
The stannate 6 coupled with 4-chlorotoluene in the
presence of the Pd(II)/IPr‚HCl catalyst. In turn, CsF, a very
21
donating IAd‚HCl was also an effective ligand for the cross-
coupling of 4-chlorotoluene and Me PhSn (Table 2, entry
). Unlike its performance in the Suzuki cross-coupling,
(
7) Applications of phosphine ligands in homogeneous catalysis: (a)
3
Parshall, G. W.; Ittel, S. Homogeneous Catalysis; Wiley and Sons: New
York, 1992. (b) Homogeneous Catalysis with Metal Phosphine Complexes;
Pignolet, L. H., Ed.; Plenum: New York, 1983.
11
4
(
8) (a) Regitz, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 725-728. (b)
(16) Fugami, K.; Ohnuma, S.-Y.; Kameyama, M.; Saotome, T.; Kosugi,
Arduengo, A. J., III; Krafczyc, R. Chem. Zeit. 1998, 32, 6-14. (c) Herrmann,
W. A.; Kocher, C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2163-2187.
M. Synlett 1999, 63-64.
(17) (a) 19F NMR spectrum of 2 equiv of TBAF/THF and 1 equiv of
Me3PhSn in DMSO-d6 after heating to 45 °C for 24 h shows the presence
of a new peak (in C6D6: -144.8 ppm vs CFCl3) due to the formation of
(
9) (a)Huang, J.; Grasa, A.; Nolan, S. P. Org. Lett. 1999, 1, 2053-2055.
(
b) Stauffer, S. R.; Lee, S.; Stambuli, J. P.; Hauck, S. I.; Hartwig, J. F.
-
+
Org. Lett, 2000, 2, 1423-1426.
[Me3PhSnF] [Bu4N] species. (b) For an example of hypervalent orga-
nostannane, see: Mallella, S. P.; Yap, S.; Sama, J. R.; Aubke, F. Inorg.
Chem. 1986, 25, 4074-4080. (c) For a silicon analogue, see: Handy, C. J.;
Lam, Y.-F.; DeShong, P. J. Org. Chem. 2000, 65, 3542-3543.
(18) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1999, 38, 2411-
2413.
(
(
10) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889-9890.
11) (a) Zhang, C.; Huang, J.; Trudell, M. T.; Nolan, S. P. J. Org. Chem.
1
999, 64, 3804-3805. (b) B o¨ hm, V. P. W.; Gst o¨ mayr, C. W. K.; Weskamp,
T.; Herrmann, W. A. J. Organomet. Chem., 2000, 595, 186-190.
(
12) (a) Lee, H. M.; Nolan, S. P. Org. Lett. 2000, 2, 1307-1309. (b)
For palladium phosphine mediated process, see for example: Mowery, M.
(19) The reasons why varied Pd to L ratios lead to different catalytic
performance are under study.
E.; DeShong, P. J. Org. Chem. 1999, 64, 1684-1688.
(
(
(
13) Mowery, M. E.; DeShong, P. Org. Lett. 1999, 1, 2137-2140.
14) Smith, P. J. Chemistry of Tin; Blackie: New York, 1998.
15) Casado, A. L.; Espinet, P. J. Am. Chem. Soc, 1998, 120, 8978-
(20) Clark, J. H. Chem. ReV. 1980, 80, 429-452.
(21) (a) Huang, J,; Schanz, H.-J.; Stevens, E. D.; Nolan, S. P. Organo-
metallics 1999, 18, 2370-2375. (b) Farina, V.; Krishnan, B. J. Am. Chem.
Soc. 1991, 113, 9585-9595.
8
985
120
Org. Lett., Vol. 3, No. 1, 2001