Palladium-catalyzed Suzuki-Miyaura couplings of potassium aryl trifluoroborates with 4-tosyloxycoumarins or 4-tosyloxyquinolin-2(1H)-one

Article abstract of DOI:10.1016/j.tetlet.2006.01.020

Pd(PPh₃)₄ catalyzed Suzuki-Miyaura cross-coupling reactions of 4-tosyloxycoumarins or 4-tosyloxyquinolin-2(1H)-one with various potassium aryl trifluoroborates afforded the corresponding 4-substituted coumarins or 4-substituted quino

Full text of DOI:10.1016/j.tetlet.2006.01.020

Tetrahedron Letters 47 (2006) 1525–1528
Palladium-catalyzed Suzuki–Miyaura couplings of potassium
aryl trifluoroborates with 4-tosyloxycoumarins or
4-tosyloxyquinolin-2(1H)-one
a
a
Jie Wu,a,b, Liang Zhang and Hong-Guang Xia
*
aDepartment of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, China
Received 8 October 2005; revised 4 January 2006; accepted 5 January 2006
Abstract—Pd(PPh3)4 catalyzed Suzuki–Miyaura cross-coupling reactions of 4-tosyloxycoumarins or 4-tosyloxyquinolin-2(1H)-one
with various potassium aryl trifluoroborates afforded the corresponding 4-substituted coumarins or 4-substituted quinolin-2(1H)-
ones in good to excellent yield.
Ó 2006 Elsevier Ltd. All rights reserved.
Among all the C–C bond forming crossing-coupling
processes, palladium-catalyzed Suzuki–Miyaura cou-
pling is one of the most important reactions.1 Its great
practical importance comes, in part, from the nontoxic,
mild, and air-, water-stable nature of the boronic acid
nucleophile. A drawback associated with the use of
boronic acids is the structural ambiguity, namely, the
formation of the trimeric anhydride (boroxine).2 The
purity of commercially available boronic acids is also
of concern. Although purification via recrystallization,
usually from water, affords a boronic acid of higher pur-
ity, removal of the water generally results in the forma-
tion of a mixture of boronic acid and the corresponding
boroxine.
aryl trifluoroborates with aryl iodides, bromides or
chlorides have been reported.4 What is missing is a sys-
tem capable of handling tosylates. Tosylates are emerg-
ing as important alternatives to aryl/vinyl triflates and
halides in Pd-catalyzed cross-coupling reactions. They
are often more stable and easier to handle than the cor-
responding triflates both in the solid state and in solu-
tion. As a direct result of these described advantages,
tosylates are becoming prominent substrates in cross-
coupling reactions. This would be of great interest if
tosylates are suitable partners in the coupling reactions
of aryl trifluoroborates.
Recently, we have witnessed the important progress of
using arenesulfonates as electrophiles for the cross-
coupling reactions although tosylates are relatively
unreactive compared to the corresponding halides and
triflates.5–11 In view of their easier preparation, increased
stability, and less expense with relative to aryl triflates, it
is of significant interest to develop a general protocol to
employ arenesulfonates for transition metal-catalyzed
Suzuki–Miyaura cross-coupling reactions of potassium
aryl trifluoroborates. In connection with a chemical ge-
netic approach of analyzing biological systems by using
interfacing libraries of natural product-like molecules
with biological assays,12 we became interested in devel-
oping new approaches to the synthesis of coumarin
and quinolin-2(1H)-one derivatives.13 Herein, we
disclose our preliminary results of palladium-catalyzed
An encouraging improvement is the use of boronate
esters and trifluoroborates. These boronic acid alterna-
tives can circumvent the above-described issues. Boro-
nate esters and trifluoroborates can be easily prepared
by treatment of boronic acids with diols, or with potas-
sium hydrogen fluorides,3 respectively. Couplings of
tetrabutylammonium aryl trifluoroborates or potassium
Keywords: Suzuki–Miyaura couplings; Potassium aryl trifluoroborates;
4-Tosyloxycoumarins; 4-Tosyloxyquinolin-2(1H)-one; Palladium
catalyst.
*
Corresponding author. Tel.: +86 2155 664619; fax: +86 2165
102412; e-mail: jie_wu@fudan.edu.cn
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.020

1526
J. Wu et al. / Tetrahedron Letters 47 (2006) 1525–1528
Suzuki–Miyaura couplings of 4-tosyloxycoumarins or
4-tosyloxyquinolin-2(1H)-one with potassium aryl tri-
fluoroborates.
water) as base, by using different palladium catalysts
(Pd(PPh3)4, PdCl2(PPh3)2, Pd(OAc)2, and Pd2(dba)3)
in the reaction of 4-tosyloxycoumarin 1a with potas-
sium phenyltrifluoroborate at 50 °C. To our delight,
we observed the formation of the corresponding prod-
uct 2a when Pd(PPh3)4 was employed, albeit in low
yield (30%) (Scheme 1). Only trace amount of product
2a was detected when other palladium catalysts were
used.
These tosylates were prepared simply from the corre-
sponding 4-hydroxycoumarins or 4-hydroxy-1-methyl-
quinolin-2(1H)-one with p-toluenesulfonyl chloride in
the presence of triethylamine. Initial studies were per-
formed in THF, with the presence of KF (1.0 M in
OTs
Ph
Pd(PPh3)4 (5 mol%)
BF3K
+
THF, KF (1.0 M in water)
O
O
O
2a
O
°
C
50
1a
30% yield
Scheme 1. Reaction of 4-tosyloxycoumarin 1a with potassium phenyltrifluoroborate catalyzed by Pd(PPh3)4.
Table 1. Palladium-catalyzed Suzuki–Miyaura cross-coupling reactions of tosylates with potassium aryl trifluoroboratesa
Entry
Substrate 1
ArBF3K
Product
Yield (%)b
86
OTs
1
C6H5BF3K
2a
O
O
1a
2
3
1a
1a
4-F–C6H4BF3K
4-Me–C6H4BF3K
2b
2c
80
89
OTs
O
Cl
4
C6H5BF3K
2d
46
O
1b
5
6
1b
1b
4-F–C6H4BF3K
4-Me–C6H4BF3K
2e
2f
92
87
OTs
F
7
C6H5BF3K
2g
61
O
O
1c
8
9
1c
1c
4-F–C6H4BF3K
4-Me–C6H4BF3K
2h
2i
86
77
OTs
O
Me
10
C6H5BF3K
2j
58
O
1d
1e
11
12
1d
1d
4-F–C6H4BF3K
4-Me–C6H4BF3K
2k
2l
89
85
OTs
O
Me
Me
13
4-Me–C6H4BF3K
2m
86
O
OTs
14
15
4-F–C6H4BF3K
2n
2o
48
68
N
CH3
O
1f
1f
4-Me–C6H4BF3K
a Reaction conditions: 4-tosylate (0.125 mmol), ArBF3K (1.5 equiv), Cs2CO3 (1.0 mL, 1.0 M in water), Pd(PPh3)4 (5 mol %), toluene (1.0 mL),
80 °C, 12 h.
b Isolated yields.

J. Wu et al. / Tetrahedron Letters 47 (2006) 1525–1528
OTs
1527
Ar
X
Pd(PPh3)4 (5 mol%)
+
ArBF3K
R
R
Cs2CO3 (1.0 M in water)
X
O
O
1.5 equiv.
°
toluene, 80 C, 12 h
X = O, NCH3
2
X = O, NCH3
1
Scheme 2. Palladium-catalyzed Suzuki–Miyaura cross-coupling reactions of tosylates with potassium aryl trifluoroborates.
Among the solvents (THF, MeCN, MeOH, toluene) and
bases (Cs2CO3, Na2CO3, KF, CsF, K3PO4, LiOH;
1.0 M in water) screened, toluene was the best solvent
and Cs2CO3 (1.0 M in water) was the best base in the
reactions. Further study showed that the reaction
worked most efficiently at 80 °C and it went to comple-
tion in 12 h (with 86% isolated yield).
1.0 M solution) were added subsequently. The reaction
mixture was stirred for 12 h at 80 °C. After the reaction
was completely monitored by TLC, the organic phase
was separated, and purified directly by flash chromato-
graphy column (silica gel) to afford the corresponding
product. Selected examples: 4-p-tolyl-2H-chromen-2-one
1
2c:14 89% yield, H NMR (500 MHz, CDCl3): d 2.46
(s, 3H), 6.36 (s, 1H), 7.24 (t, J = 7.5 Hz, 1H), 7.35 (m,
4H), 7.40 (d, J = 8.0 Hz, 1H), 7.53 (m, 2H). 13C NMR
(125.7 MHz) d 161.1, 156.0, 154.5, 140.2, 132.6, 132.1,
129.8, 128.7, 127.3, 124.3, 119.4, 117.6, 115.2, 21.6.
MS [C16H12O2], m/z (M++1): calcd 237, found 237.
6,7-Dimethyl-4-p-tolyl-2H-chromen-2-one 2m: 86% yield,
1H NMR (500 MHz, CDCl3): d 2.23 (s, 3H), 2.35 (s,
3H), 2.46 (s, 3H), 6.27 (s, 1H), 7.17 (s, 1H), 7.23 (s,
1H), 7.35 (t, J = 9 Hz, 4H). 13C NMR (125.7 MHz): d
161.4, 155.7, 152.7, 141.9, 139.7, 132.9, 132.8, 129.5,
128.4, 127.0, 117.9, 116.8, 113.9, 21.4, 20.2, 19.3. MS
[C18H16O2], m/z (M+): calcd 264, found 264. HRMS:
Anal. Calcd for C18H16O2, 264.1150. Found, 264.1156.
A variety of 4-(p-toluenesulfonyloxy)coumarins and
potassium aryl trifluoroborates have thus been exam-
ined for palladium-catalyzed cross-coupling reactions
under the optimized conditions, and the results are sum-
marized in Table 1. As shown there, the conditions have
proved to be efficient for coupling a range of tosylates
with potassium aryl trifluoroborates (Table 1 and
Scheme 2). Complete conversion and good to excellent
isolated yields were observed for all arenesulfonates em-
ployed. Potassium aryl trifluoroborates either with elec-
tron-rich or electron-withdrawing substitutions all gave
similar yields. For example, 80% or 89% yield of product
2b or 2c was obtained when 4-tosyloxycoumarin 1a
reacted with potassium 4-fluorophenyl trifluoroborate
or potassium 4-methylphenyl trifluoroborate (entries 2
and 3). Furthermore, 4-(p-toluenesulfonyloxy)-1-
methyl-quinolin-2(1H)-one 1f was tested suitable in the
cross-coupling reactions although the yields were lower
comparing coumarin substrates (entries 14 and 15).
1
1-Methyl-4-p-tolylquinolin-2(1H)-one 2o: 68% yield, H
NMR (500 MHz, CDCl3): d 2.45 (s, 3H), 3.78 (s, 3H),
6.69 (s, 1H), 7.18 (t, J = 7 Hz, 1H), 7.31 (m, 4H), 7.43
(d, J = 8.5 Hz, 1H), 7.59 (m, 2H). 13C NMR
(125.7 MHz): d 162.1, 151.0, 140.4, 138.7, 134.2, 130.6,
129.3, 128.9, 127.8, 122.6, 121.9, 120.7, 114.5, 29.5,
21.3. MS [C17H15NO], m/z (M+): calcd 249, found
249. HRMS: Anal. Calcd for C17H15NO, 249.1154.
Found, 249.1168.
Although the mechanism is not clear since there is no
supporting evidence at present, a possible mechanistic
rationalization for the reaction is proposed. The initial
event was an oxidative addition of palladium(0) to the
tosylate. The intermediate generated then underwent
transmetalation in the presence of aryl trifluoroborates,
followed by a reductive elimination to afford the corre-
sponding product and palladium(0), which completed
the catalytic cycle.
Acknowledgments
Financial support from National Natural Science Foun-
dation of China (20502004), Ministry of Education of
China, the Science, and Technology Commission of
Shanghai Municipality, and Fudan University is grate-
fully acknowledged.
In conclusion, we have described efficient Suzuki–Miya-
ura cross couplings of tosylates with potassium aryl tri-
fluoroborates catalyzed by Pd(PPh3)4. The advantage of
this method includes good substrate generality, the use
of air-stable, inexpensive tosylate under mild conditions,
and experimentally operational ease. The reaction
employing aryl arenesulfonates as substrates is currently
under investigation in our research group, which will be
reported in due course.
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