Palladium catalyzed atom-efficient cross-coupling reactions of triarylbismuths with aryl iodides and aryl triflates

Article abstract of DOI:10.1016/j.tetlet.2007.07.107

The atom-efficient cross-coupling of triarylbismuths with aryl iodides or aryl triflates using catalytic Pd(OAc)₂/PPh₃ and K₃PO₄ as base in DMF at 90 °C to afford the corresponding functionalized biaryls in high yields is reported.

Full text of DOI:10.1016/j.tetlet.2007.07.107

Tetrahedron Letters 48 (2007) 6644–6647
Palladium catalyzed atom-efficient cross-coupling reactions
of triarylbismuths with aryl iodides and aryl triflates
*
Maddali L. N. Rao, Debasis Banerjee and Deepak N. Jadhav
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Received 3 March 2007; revised 12 July 2007; accepted 20 July 2007
Available online 27 July 2007
Abstract—The atom-efficient cross-coupling of triarylbismuths with aryl iodides or aryl triflates using catalytic Pd(OAc) /PPh and
2
3
K
ꢁ
3
PO
4
as base in DMF at 90 ꢀC to afford the corresponding functionalized biaryls in high yields is reported.
2007 Elsevier Ltd. All rights reserved.
The cross-coupling reactions of organometallic reagents
with electrophilic reagents is an important route for car-
bon–carbon bond formation. The versatility of these
Currently, different activators in the form of a base or a
fluoride reagent in different solvents are required.
4
b
Thus, in our efforts to establish the cross-coupling reac-
tivity of triarylbismuths with aryl iodides, an initial
1
methods have been well exploited in organic synthesis.
4
d
The cross-coupling of aryl halides and aryl triflates with
aryl organometallic reagents is a useful methodology for
the synthesis of various functionalized biaryls. Biaryls
are important due to their presence in a variety of natu-
ral products, pharmaceuticals and in liquid crystalline
materials applications. The Suzuki coupling involving
organoboron reagents, the Stille coupling using orga-
anotin and the Negishi coupling with organozinc
screening was performed using Pd(OAc) as catalyst.
2
The cross-coupling reaction of p-iodoacetophenone
a,b
Table 1. Screening conditions
Pd(OAc)2
3
Ac
I + BiPh3
3 Ac
o
9
0 C, 1 h
1
,2
c
reagents are popular methods for biaryl synthesis.
Entry
Solvent
Base
Conv. (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
DMF
DMF
DMF
THF
NaOAc
Ba(OH)
DABCO
57
43
65
0
0
0
The development of atom-efficient organometallic re-
agents is important as many of these reagents are used
in industrial scale synthesis. Atom-efficient reagents
2
2
K
3
K
3
K
3
K
3
K
3
K
3
K
3
K
3
K
3
PO
PO
PO
PO
PO
PO
PO
PO
PO
4
4
4
4
4
4
4
4
4
which can react with more than 1 equivalent of electro-
CH
3
CN
3
Toluene
Dioxane
DME
NMP
DMF
DMF
DMF
DMF
DMF
philic reagents such as triarylindiums and triarylbis-
7
muths would lower the stoichiometric loading of
organometallic reagents. Reactions of triarylbismuths
with electrophilic reagents under metal catalyzed condi-
22
88
94
0
53
1
1
1
1
4
,5
tions are of present interest. Hence, we report a new
palladium catalyzed protocol for the cross-coupling of
triarylbismuths with aryl iodides or aryl triflates for
the synthesis of various functionalized biaryls.
d
e
None
30
87
f
14
K PO
3
4
a
Conditions: equiv ratios are based on BiAr
3.5 equiv), Pd(OAc) (0.1 equiv)/PPh
solvent (3 mL), 90 ꢀC.
3
: BiAr
3
(1 equiv), Ar-I
To date, a generalized palladium catalyzed protocol
for the cross-coupling of triarylbismuths with aryl
bromides, aryl iodides and aryl triflates is not available.
(
2
3
(0.4 equiv), base (6 equiv),
b
Homo-coupled biphenyls resulted from triarylbismuths when no
cross-coupling occurred.
Based on GC analysis.
c
d
e
f
Keywords: Cross-coupling; Atom-efficient; Triarylbismuth; Aryl iod-
ides; Aryl triflates.
Control reaction without Pd(OAc)
Control reaction without PPh
With 4 equiv of K PO
2
.
*
Corresponding author. Tel./fax: +91 512 2597532; e-mail: maddali@
iitk.ac.in
3
.
3
4
.
0040-4039/$ - see front matter ꢁ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.107

M. L. N. Rao et al. / Tetrahedron Letters 48 (2007) 6644–6647
6645
(
3.5 equiv) was examined with triphenylbismuth under
30% conversion to the product occurred (entry 13).
Under similar conditions with K PO (4 equiv), an 87%
various conditions, Table 1.
3
4
conversion to the cross-coupled product was obtained
(entry 14). As the solubility of the base was not good
in DMF, we found it was beneficial to use 6 equiv of
base to obtain a high cross-coupling conversion between
the aryl iodide (3.5 equiv) and triphenylbismuth
(1 equiv) at 90 ꢀC in 1 h (entry 10). The present protocol
was found to be very efficient, as a high conversion to 4-
acetylbiphenyl was obtained in a very short reaction
From the initial screening, it was found that bases such
as sodium acetate, barium hydroxide and DABCO gave
moderate conversion to the cross-coupled product,
4
-acetylbiphenyl in DMF (entries 1–3). Further screen-
ing with K PO as base afforded different extents of
3
4
conversion in various solvents. In solvents such as tetra-
hydrofuran, acetonitrile, toluene, dioxane, 1,2-dimeth-
oxyethane, poor or no conversion to a cross-coupled
product occurred (entries 4–8). Solvents such as NMP
4
b
time under relatively mild conditions.
(
entry 9) and DMF (entry 10) resulted in high conver-
Encouraged by this, further screening of the reactions of
various aryl iodides with triarylbismuths was carried out
to determine the generality of the present protocol (Ta-
sion to 4-acetylbiphenyl with K PO as base. A control
experiment carried out in the absence of Pd(OAc) did
not afford any cross-coupled product (entry 11). The
3
4
2
6
ble 2). As the rate of oxidative addition of aryl triflates
absence of PPh as ligand gave only a 53% conversion to
to Pd(0) falls in between aryl iodides and aryl bromides,
3
1
f
4
-acetylbiphenyl (entry 12). Further, we have carried
similar cross-coupling reactivity with aryl triflates was
expected. Hence, we studied the cross-coupling reactiv-
out reactions involving varied amounts of base equiva-
lents. It was found that in the absence of K PO , only
6
ity of aryl triflates under the same conditions and the
3
4
Table 2. Synthesis of various functionalized biphenyls
Pd(OAc)2 (0.1 equiv)
PPh (0.4 equiv)
3
3
X
+
Bi
3
K PO (6 equiv)
3
4
R1
R2
3
o
R1
R2
DMF, 90 C, 1 h
a,b
Yield (%)
Entry
1
Ar-X
H C
BiAr
4-H
3
Product
3
H C
3
I
91
O
O
H C
3
2
3
4
5
4-OCH
3
OCH3
CH3
F
90
77
91
82
O
H C
3
4-CH
3
O
H C
3
4-F
O
H C
3
4-Cl
Cl
O
H C
3
6
7
3-OCH
3
95
68
O
OCH3
H C
3
H C
3
OTf
4-H
O
O
8
9
Cl
I
4-H
Cl
77
90
4-OCH
3
Cl
Cl
OCH3
CH3
1
0
4-CH
3
90
(continued on next page)

6646
M. L. N. Rao et al. / Tetrahedron Letters 48 (2007) 6644–6647
Table 2 (continued)
a,b
Yield (%)
Entry
Ar-X
BiAr
3
Product
1
1
1
1
1
1
1
1
1
2
2
2
1
2
3
4
5
6
7
8
9
0
1
2
Cl
OTf
4-OCH
3
Cl
OCH3
CH3
79
73
94
71
73
73
58
61
61
82
44
56
4-CH
3
Cl
O N
I
4-H
O N
2
2
O N
OTf
4-H
O N
2
2
4-OCH
3
O N
OCH3
2
4-CH
3
O N
CH3
2
H C
I
4-H
H C
3
3
H C
OTf
4-OCH
3
H C
OCH3
3
3
4-H
H C
3
F
OTf
4-OCH
3
F
OCH3
H CO
OTf
4-H
H CO
3
3
NC
NC
OTf
4-H
NC
NC
I
2
2
3
4
4-H
85
83
OTf
OCH3
4-OCH
3
NC
NC
NC
NC
2
2
2
5
6
7
I
4-H
4-H
4-H
81
45
H CO
I
H CO
3
3
F3C
I
F3C
83
a
Conditions: equiv ratios are based on BiAr
3 mL), 90 ꢀC, 1 h.
3
: BiAr
3
(1 equiv), Ar-X (3.5 equiv), Pd(OAc)
2
(0.1 equiv)/PPh
3
(0.4 equiv), K
3
PO
4
(6 equiv), DMF
(
b
1
13
Isolated yields after purification by column chromatography. All the products were characterized by H, C NMR and IR spectroscopy and by
comparison with the literature data.
results are given in Table 2. The cross-coupling reaction
p-methyl, p-fluoro, p-chloro, p-methoxy and m-methoxy
of p-iodoacetophenone with triarylbismuths containing
substituents produced the corresponding functionalized

M. L. N. Rao et al. / Tetrahedron Letters 48 (2007) 6644–6647
6647
biphenyls in high yields (entries 1–6). The cross-coupling
reaction of p-acetylphenyl triflate with triphenylbismuth
afforded a moderate yield of the product (entry 7). In
contrast, p-chlorophenyl iodide and p-chlorophenyl tri-
flate reacted well giving good to high yields of the
cross-coupled products (entries 8–12). Electron-deficient
p-nitrophenyl iodide and p-nitrophenyl triflate produced
the corresponding cross-coupled biphenyls in good
yields (entries 13–16). The cross-coupling reactions with
electron rich p-tolyl iodide and p-tolyl triflate produced
moderate yields of the corresponding biphenyls (entries
K.; Kashinath, D. Tetrahedron 2002, 58, 9633–9695; (c)
Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: New York, 1998; (d)
Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44,
3
66–374; (e) Stanforth, S. P. Tetrahedron 1998, 54, 263–303;
(
f) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire,
M. Chem. Rev. 2002, 102, 1359–1469; (g) Miyaura, N.;
Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
. (a) Corbet, J. P.; Mignani, G. Chem. Rev. 2006, 106, 2651–
2710; (b) Rouhi, A. M. Chem. Eng. News 2004, 82, 49–58.
3. (a) Perez, I.; Sestelo, J. P.; Sarandeses, L. A. Org. Lett.
1999, 1, 1267–1269; (b) Perez, I.; Sestelo, J. P.; Sarandeses,
L. A. J. Am. Chem. Soc. 2001, 123, 4155–4160; (c) Pena, M.
A.; Sestelo, J. P.; Sarandeses, L. A. J. Org. Chem. 2007, 72,
2
1
7–19). Substituted phenyl triflates possessing a p-meth-
oxy or p-cyano group gave 44% and 56% yields (entries
1 and 22), while that with a p-fluoro substituent gave
1
271–1275; (d) Pena, M. A.; Sestelo, J. P.; Sarandeses, L. A.
2
Synthesis 2005, 3, 485–492.
an 82% yield of the cross-coupled product (entry 20).
m-Cyanophenyl iodide and m-cyanophenyl triflate also
produced high yields with different triarylbismuths
4
. (a) Organobismuth Chemistry; Suzuki, H., Matano, Y.,
Eds.; Elsevier: Amsterdam, 2001; (b) Rao, M. L. N.;
Yamazaki, O.; Shimada, S.; Tanaka, T.; Suzuki, Y.;
Tanaka, M. Org. Lett. 2001, 3, 4103–4105; (c) Rao, M. L.
N.; Venkatesh, V.; Jadhav, D. N. Tetrahedron Lett. 2006,
47, 6975–6978; (d) Rao, M. L. N.; Banerjee, D.; Jadhav, D.
N. Tetrahedron Lett. 2007, 48, 2707–2711; (e) Asano, R.;
Moritani, I.; Fujiwara, Y.; Teranishi, S. Bull. Chem. Soc.
Jpn. 1973, 46, 2910–2911; (f) Kawamura, T.; Kikukawa, K.;
Takagi, M.; Matsuda, T. Bull. Chem. Soc. Jpn. 1977, 50,
(
entries 23 and 24). The cross-coupling of p-methoxy-
phenyl iodide gave a moderate yield of the correspond-
ing cross-coupled product (entry 26). The reactivity of
p-cyanophenyl iodide and p-trifluoromethylphenyl
iodide produced high yields of cross-coupled products
(
entries 25 and 27). In this study, electron-deficient aryl
iodides and aryl triflates reacted efficiently with triaryl-
bismuths furnishing high yields of the corresponding
cross-coupled products. It is noteworthy that electron-
rich aryl iodides and aryl triflates which are otherwise
known to be less reactive also afforded moderate yields
2
021–2024; (g) Barton, D. H. R.; Ozbalik, N.; Ramesh, M.
Tetrahedron 1988, 44, 5661–5668; (h) Wada, M.; Ohki, H.
J. Synth. Org. Chem. Jpn. 1989, 47, 425–435; (i) Ohe, T.;
Tanaka, T.; Kuroda, M.; Cho, C.-S.; Ohe, K.; Uemura, S.
Bull. Chem. Soc. Jpn. 1999, 72, 1851–1855.
4
b
of the cross-coupled products with triarylbismuths.
5. Other organobismuths for carbon–carbon bond formation:
(a) Rao, M. L. N.; Shimada, S.; Tanaka, M. Org. Lett.
1999, 1, 1271–1273; (b) Rao, M. L. N.; Shimada, S.;
Yamazaki, O.; Tanaka, M. J. Organomet. Chem. 2002, 659,
Evidently, the cross-coupling reactivity of the electroni-
cally different triarylbismuths was proved to be efficient
with different aryl iodides or aryl triflates under the pres-
ent conditions.
1
17–120; (c) Shimada, S.; Yamazaki, O.; Tanaka, T.; Rao,
M. L. N.; Suzuki, Y.; Tanaka, M. Angew. Chem., Int. Ed.
003, 42, 1845–1848; (d) Yamazaki, O.; Tanaka, T.;
Shimada, S.; Suzuki, Y.; Tanaka, M. Synlett 2004, 1921–
924.
2
In conclusion, we have disclosed a palladium catalyzed,
atom-efficient cross-coupling reaction of triarylbismuths
with aryl iodides and aryl triflates. The catalytic proto-
col developed involves the use of a readily available
metal catalyst, ligand and base. In addition, the short
reaction time is an added advantage.
1
6
. Representative procedure for the cross-coupling reaction of
aryl iodides and triflates (Table 2): A hot oven-dried
Schlenk tube was charged with p-iodoacetophenone
(0.215 g, 0.87 mmol) and triphenylbismuth (0.110 g,
0
.25 mmol). To this, K
3
PO
4
(0.318 g, 1.5 mmol), PPh
2
(0.0056 g, 0.025 mmol) and
3
(
0.026 g, 0.1 mmol), Pd(OAc)
solvent DMF (3 mL) were added under a nitrogen atmo-
Acknowledgements
sphere. The mixture was stirred at 90 ꢀC in an oil bath for
1
h. The contents were cooled to room temperature and the
We thank DST, India, and IIT-Kanpur for supporting
this work. D.B. and D.N.J. thank IIT-Kanpur and
CSIR, New Delhi, respectively, for research fellowships.
reaction was quenched with dil HCl (10 mL) and extracted
with ethyl acetate (3 · 10 mL). The combined organic
extract was washed with water, brine and dried over
4
anhydrous MgSO . The organic extract was concentrated
under reduced pressure. The crude product thus obtained
was further purified by column chromatography on silica
gel (100–200 mesh) using hexane–ethyl acetate (8:2) as
eluent to afford pure 4-acetylbiphenyl (0.133 g) in 91%
References and notes
1
. Selected references on metal catalyzed coupling reactions,
see: (a) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew.
Chem., Int. Ed. 2005, 44, 4442–4489; (b) Kotha, S.; Lahiri,
1
13
yield. The product was characterized by comparing H,
C
NMR and IR data with the reported data.