Oxime-palladacycle-catalyzed suzuki-miyaura arylation and alkenylation of aryl imidazolesulfonates under aqueous and phosphane-free conditions

Article abstract of DOI:10.1002/ejoc.201200368

Aryl and hetaroaryl imidazole-1-sulfonates are efficiently arylated and alkenylated with aryl- and alkenylboronic acids and potassium trifluoroborates by using 0.5 mol-% palladacycles 1 or Pd(OAc)₂ at 110 °C under aqueous and phosphane-free conditions. Reactions can be performed by using conventional or microwave heating, leading to biaryls, stilbenes, and alkenylarenes in good to high yields, and high regio- and diastereoselectivities. The optimized methodology allows in situ phenol sulfonylation and one-pot Suzuki arylation or alkenylation as well as orthogonal functionalization of halogen-containing aryl imidazolesulfonates.

Full text of DOI:10.1002/ejoc.201200368

FULL PAPER
DOI: 10.1002/ejoc.201200368
Oxime–Palladacycle-Catalyzed Suzuki–Miyaura Arylation and Alkenylation of
Aryl Imidazolesulfonates under Aqueous and Phosphane-Free Conditions
[a]
[a]
[a]
José Francisco Cívicos, Diego A. Alonso,* and Carmen Nájera*
Dedicated to the memory of Professor Balbino Mancheño
Keywords: Alkenes / Biaryls / Cross-coupling / Metallacycles / Microwave chemistry / Synthetic methods
Aryl and hetaroaryl imidazole-1-sulfonates are efficiently ar-
ylated and alkenylated with aryl- and alkenylboronic acids
enes, and alkenylarenes in good to high yields, and high
regio- and diastereoselectivities. The optimized methodology
and potassium trifluoroborates by using 0.5 mol-% pallada- allows in situ phenol sulfonylation and one-pot Suzuki aryl-
cycles 1 or Pd(OAc)
phane-free conditions. Reactions can be performed by using
conventional or microwave heating, leading to biaryls, stilb-
2
at 110 °C under aqueous and phos-
ation or alkenylation as well as orthogonal functionalization
of halogen-containing aryl imidazolesulfonates.
Introduction
The palladium-catalyzed Suzuki–Miyaura cross-coupling
reaction constitutes one of the most powerful carbon–car-
bon bond-forming transformations.[1] Although cross-cou-
plings of aryl halides are most common, significant efforts
are underway to make the Suzuki coupling a greener chemi-
cal process by using inexpensive, readily available, and less
Scheme 1. Suzuki C–O activation catalyzed by Ni or Pd.
toxic hydroxylated arene derivatives[
2,3]
as electrophiles.
[4]
Traditionally, the palladium-catalyzed Suzuki–Miyaura so often in the Suzuki coupling of phenol derivatives, with
cross-coupling reaction of enols, phenols, and hydroxylated the presence of ancillary phosphane ligands being manda-
arenes has usually involved their prior transformation into tory for successful coupling. For instance, aryl imid-
triflates due to the superior performance of these deriva- azolesulfonates have been demonstrated to be efficient elec-
tives as electrophilic partners.[ However, triflates are sub- trophilic coupling partners in the Suzuki reaction with aryl-
strates with limited stability. Thus, a number of recent stud- boronic acids by employing bidentate phosphanes 1,1Ј-
ies have shown the ability of other groups, such as mesylates bis(diphenylphosphanyl)ferrocene (dppf) and BINAP, un-
5]
[
6,7]
[8]
[8a]
[19,20]
and sulfonates,
carbamates, carbonates,
carboxyl- der high catalyst loadings (5–10 mol-% Pd).
[
7a,9,10]
[11]
[12,13]
ates,
methyl ethers, phosphonium salts,
phos-
and N,N-di- tives mentioned above has been largely developed by using
to participate in the Suzuki reac- traditional organic solvents, which greatly reduces the envi-
The Suzuki coupling of the hydroxylated arene deriva-
[
14]
[15,16]
[17]
phoramides,
phosphates,
borates,
[
8a,8c,18]
alkyl-O-sulfamates,
tion (Scheme 1).
[
21]
ronmental sustainability of the process.
In our research
These electrophiles have usually been employed in the group, the Suzuki reaction has been studied during the past
synthesis of biaryls by using high loadings of nickel cata- decade by using oxime–palladacycles 1 (Figure 1) or
lysts in the presence of phosphane ligands. Except for mesy- Pd(OAc) as efficient precatalysts for the coupling of vinyl
2
lates and tosylates, palladium catalysis has not been used
[
a] Departamento de Química Orgánica & Instituto de Síntesis
Orgánica, Universidad de Alicante
Carretera de San Vicente del Raspeig s/n, 03690 San Vicente
del Raspeig, Alicante, Spain
Fax: +34-965-903549
E-mail: diego.alonso@ua.es
cnajera@ua.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200368.
Figure 1. Oxime–palladacycle catalysts.
3670
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 3670–3676

Suzuki–Miyaura Arylation and Alkenylation of Aryl Imidazolesulfonates
and aryl halides with boronic acids and potassium tri- Table 1. Reaction conditions study.[a]
fluoroborates in organic and aqueous solvents.[
22–25]
Regarding C–O activation, we have recently disclosed in
a preliminary communication, a general phosphane-free ox-
ime–palladacycle-catalyzed Suzuki cross-coupling reaction
of electron-rich, electron-poor, and hindered aryl imid-
azolesulfonates with arylboronic acids and potassium aryl-
trifluoroborates under aqueous and low catalyst loading
[
26]
conditions. Herein, we report a full account of the biaryl
synthesis as well as the results obtained for the alkenylation
of aryl and heteroaryl imidazole-1-sulfonates under aque-
ous conditions by using conventional or microwave heat-
[
27]
ing.
Entry
2
RBX
Catalyst
Product,
Yield [%]
[
b]
Results and Discussion
1
2
3
4
5
6
7
8
9
2aa
2ab
2ac
2ad
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
2ae
PhB(OH)
PhB(OH)
PhB(OH)
2
2
2
1a
3a, Ͻ 5
3a, Ͻ 5
3a, Ͻ 5
3a, Ͻ 5
3a, 67
1a
Initial Suzuki cross-coupling studies were carried out
with 1-naphthol derivatives 2 (Table 1). The cross-coupling
1a
PhB(OH)2
1a
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)2
PhB(OH)
2
2
2
2
1a
of 2 (1 equiv.) with phenylboronic acid (1.5 equiv.) was ini-
1a[
c]
3a, Ͻ 5
3a, Ͻ 5
3a, 84
tially performed by using catalyst 1a[
28]
(1 mol-% Pd) and
1a[
d]
KOH (2 equiv.) as base in a 3:1 MeOH/H O mixture as sol-
vent in the presence of tetra-n-butylammonium bromide
2
Pd(OAc)
2
1b
3a, Ͼ 99
[
e]
(
TBAB; 20 mol-%) as phase-transfer agent at 110 °C. As 10
2
1b
3a, Ͼ 99
3a, 89
11
12
13
14
PhBF
PhBF
PhBF
3
3
3
K
K
K
1a
depicted in Table 1 (Entries 1–5), only imidazolesulfonate
derivative 2ae showed reactivity under these conditions, af-
fording 1-phenylnaphthalene (3a) in 67% isolated yield
1b
3a, 45
Pd(OAc)
1a
2
3a, 10
[f]
[f]
PhB[(OCOCH
PhB[{OC(Me) }]
(E)-PhCH=CHB(OH)
(E)-PhCH=CHB(OH)
(E)-PhCH=CHB(OH)
(E)-PhCH=CHB(OH)
(E)-PhCH=CHB(OH)2 1a
(E)-PhCH=CHBF
(E)-PhCH=CHBF
2
)
2
NMe]
2
2
3a, 50
3a, 39
4a, 72
4a, 85
4a, 15
4a, 65
4a, 74
4a, 72
4a, 70
[
29]
(Table 1, Entry 5).
Once it was demonstrated that the 15
1b
2
16
17
18
19
2
1b
imidazole-1-sulfonate was the best electrophile in the pro-
cess, an optimization of the reaction conditions was carried
out. No reaction took place when the coupling was per-
formed in aqueous acetone or in neat water (Table 1, En- 20
tries 6 and 7). Regarding catalysts, Pd(OAc)2 afforded a 21
[
e]
2
2
2
1b
Pd(OAc)
Pd(OAc)
2
[e]
2
[
[
e]
e]
3
K
K
1b
1b
2
2
3
higher yield (84%) in the reaction (compare Table 1, En-
tries 5 and 8). To our surprise, the yield was improved sub- [a] Reaction conditions: Pd catalyst (1 mol-% Pd), 2 (0.1 mmol),
RBX (0.15 mmol), TBAB (20 mol-%), KOH (0.2 mmol), MeOH/
stantially (99%) when palladacycle 1b, a catalyst that usu-
ally performs better in organic solvents,[
23]
H
2
O (3:1), 110 °C, 24 h. [b] Isolated yield after flash chromatog-
raphy. [c] Reaction solvent: Me CO/H O (3:2). [d] Reaction solvent:
O. [e] Reaction performed under microwave irradiation (40 W,
was used
2
2
(Table 1, Entry 9). In the presence of catalyst 1b, the reac-
H
2
tion could also be performed under microwave irradiation 110 °C, 30 min). [f] Reaction time: 2 d.
conditions (40 W irradiation to heat to 110 °C and main-
tained at this temperature for 30 min), affording compound
3a in quantitative yield after this short time (Table 1, En- higher when the reaction was carried out under microwave
try 10). The optimized results obtained with different boron irradiation (Table 1, Entries 16–22). Palladium(II) acetate
electrophiles are shown in Entries 11–15. Potassium phenyl- also showed better activity under microwave irradiation
trifluoroborate afforded compound 3a in 89% isolated yield than under conventional heating, although 4a was obtained
by using catalyst 1a (Table 1, Entry 11). With this nucleo- in lower yields than when palladacycle 1b was used (com-
phile, catalyst 1b and Pd(OAc) were less effective than 1a, pare Table 1, Entries 16 and 17 with 18 and 19). Finally, use
2
affording compound 3a in 45 and 10% yield, respectively of oxime–palladacycle 1a afforded 4a in 74% yield under
(Table 1, Entries 12 and 13). Low yields were also obtained microwave irradiation; a result that confirmed palladacycle
after 2 d when imidazolesulfonate 2ae was treated with 1b was also the most efficient catalyst for the alkenylation
phenylboronic acid N-methyliminodiacetate (MIDA) ester process (compare Table 1, Entries 17 and 20).
(
50%; Table 1, Entry 14) and phenylboronic acid pinacol
The scope of this methodology was then examined under
the optimized reaction conditions. Initially, the coupling of
ester (39%; Table 1, Entry 15).
The alkenylation of 2ae with styrylboron nucleophiles a range of arylboronic acids and potassium aryltrifluoro-
followed a trend similar to that observed in the arylation borates with naphthalen-1-yl-1H-imidazole-1-sulfonate
cross-coupling. Good yields were obtained for both boronic (2ae) was studied by using conventional (110 °C, 24 h) and
acids and potassium trifluoroborates, and were usually microwave heating (40 W, 110 °C, 30 min). As depicted in
Eur. J. Org. Chem. 2012, 3670–3676
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3671

J. F. Cívicos, D. A. Alonso, C. Nájera
FULL PAPER
Table 2. Pd-catalyzed Suzuki arylations of 2ae.[a]
Table 2, biaryl derivatives 3a–f were isolated in good to ex-
cellent yields, which were generally higher for boronic acids
than for potassium trifluoroborates, and also proceeded
better under microwave irradiation than with conventional
heating.
With respect to the catalyst, use of palladacycle 1b usu-
ally afforded better results than 1a, although no clear corre-
lation between the catalyst and the boron source could be
established from parallel experiments. Thus, further studies
on the reaction scope and utility of the method were always
optimized with respect to the catalyst. Electron-donating
Entry ArBX
1
3
Δ Yield MW yield
%][b,c]
[b,d]
[
[%]
1
2
3
4
5
6
7
8
9
1
1
1
1
PhB(OH)
PhB(OH)
2
2
1a
1b
1a
1b
1a
1b
1a
1b
1b
1b
1b
1b
1b
3a
3a
3a
3a
3b
3b
3b
3b
3c
3d
3d
3e
3f
67
76
Ͼ 99
89
45
90
76
61
72
75
66
64
69
55
100
89
88
79
95
70
82
90
79
72
73
69
(Table 2, Entries 5–9) and electron-withdrawing groups
PhBF
PhBF
3
K
K
6
6
6
6
3
(Table 2, Entries 10 and 11) on the phenyl ring of the nu-
cleophile had little impact on the efficiency of the reaction,
although lower yields (64–79%) were observed for the lat-
ter. Finally, heterocyclic potassium pyrid-3-yl- and thien-3-
yltrifluoroborates also showed good reactivity in this pro-
cess, affording compounds 3e and 3f in 73 and 69% isolated
yields, respectively, by using microwave irradiation (Table 2,
Entries 12 and 13).
4-MeC
4-MeC
4-MeC
4-MeC
H
4
4
4
4
B(OH)
B(OH)
2
2
H
H
H
BF
BF
3
K
K
3
4-MeOC
6
H
4
B(OH)
B(OH)
BF
2
0
1
2
3
4-CF
4-CF
3
C
C
6
H
H
4
2
3
6
4
3
K
3-pyridylBF
3-thienylBF
3
K
3
K
Regarding the electrophilic component (Table 3), high
isolated yields (72–96%) were obtained in the microwave-
assisted 1b-catalyzed cross-coupling of arylboronic acids
[
a] Reaction conditions: Pd catalyst (1 mol-% Pd), 2ae (0.1 mmol),
ArBX (0.15 mmol), TBAB (20 mol-%), KOH (0.2 mmol). [b] Iso-
lated yield after flash chromatography. [c] Reaction performed at
1
10 °C for 24 h. [d] Reaction performed under microwave (MW) with neutral, electron-rich, and electron-poor phenyl imid-
irradiation (40 W, 110 °C, 30 min).
azolesulfonates (Table 3, Entries 1–8). For comparison,
Table 3. Pd-catalyzed Suzuki arylation of 2.
[a] Isolated yield after flash chromatography. The isolated yield under conventional thermal heating (110 °C, 24 h) is given in parentheses.
3
672 Eur. J. Org. Chem. 2012, 3670–3676
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Suzuki–Miyaura Arylation and Alkenylation of Aryl Imidazolesulfonates
some of the cross-coupling reactions were also carried out col (Table 1, Entry 17) by using microwave irradiation
by using conventional heating, affording similar or lower (Table 4). In general, good isolated yields (62–93%) were
yields (with longer reaction times) under otherwise identical obtained for the regio- and stereoselective synthesis of stilb-
reaction conditions (Table 3, entries 1–4 and 6, 7). The pro- ene and styrene derivatives 4, regardless of which nucleo-
cess was also effective for the coupling of sterically hindered phile was employed. The coupling of naphthalen-1-yl 1H-
electrophiles such as 3,5-dimethylphenyl 1H-imidazole-1- imidazole-1-sulfonate (2ae) with potassium trans-decen-1-
sulfonate (2ee), 2-(trifluoromethyl)phenyl 1H-imidazole-1- yltrifluoroborate afforded the corresponding trans-1-(dec-1-
sulfonate (2he), and 2-cyanophenyl 1H-imidazole-1-sulf- en-1-yl)naphthalene (4b) in 88% yield (Table 4, Entry 1).
onate (2ie) (Table 3, Entries 4, 7, and 8). In all these exam- We also found that deactivated phenyl imidazole-1-sulf-
ples, the efficiency of the microwave irradiation was clearly onates, such as those derived from 4-methoxyphenol
demonstrated, in particular, with the sterically demanding (Table 4, Entries 2–4), 4-methylphenol (Table 4, Entry 5),
imidazolesulfonate 2ee, which afforded 3,5-dimethyl-1,1Ј-bi- and 3,5-dimethylphenol (Table 4, Entry 6), were success-
phenyl (3i) in 72% yield (Table 3, Entry 4). The result illus- fully alkenylated to yield compounds 4c–f in good to excel-
trated in Entry 8 was especially attractive, because the ob- lent yields (77–92%). Challenging electrophiles, such as the
tained product, 2-cyano-4Ј-methylbiphenyl (3m), is a key in- sterically hindered and electron-rich o-tolyl 1H-imidazole-
termediate in the synthesis of angiotensin II receptor antag- 1-sulfonate (2le) and 2,6-dimethylphenyl 1H-imidazole-1-
[
30]
onists that are used for the treatment of hypertension.
sulfonate (2ee), were also successfully alkenylated with
Finally, heterocyclic 2-phenylpyridine (3n) could also be trans-styrylboronic acid, trans-hept-1-en-1-ylboronic acid,
prepared in a good isolated yield (72%) under aqueous con- and potassium trans-hept-1-en-1-yltrifluoroborate to afford
ditions from pyridin-2-yl 1H-imidazole-1-sulfonate (2je) compounds 4g, 4h, and 4i, respectively, in yields ranging
and phenylboronic acid (Table 3, Entry 9).
from 62 to 90% (Table 4, Entries 7–10). The optimized re-
Concurrent with the above substrate scope studies on the action conditions were also shown to be useful for the cou-
synthesis of biaryl derivatives from aryl imidazolesulfo- pling of electron-deficient electrophiles, with 4-nitrostilbene
nates, the Pd-catalyzed alkenylation of these electrophiles being obtained in 93% yield from the coupling of trans-
under aqueous conditions was then targeted.[ Thus, a styrylboronic acid and 4-nitrophenyl 1H-imidazole-1-sulf-
range of aryl imidazolesulfonates were cross-coupled with onate (2fe) (Table 4, Entry 11). Finally, alkenylation of het-
various β-aryl- and β-alkyl-substituted alkenylboronic acids erocyclic pyridin-2-yl 1H-imidazole-1-sulfonate (2je) with
and potassium trifluoroborates under the optimized proto- trans-styrylboronic acid and potassium trans-decen-1-yltri-
31]
Table 4. Pd-catalyzed Suzuki alkenylation of 2.
[a] Isolated yield after flash chromatography.
Eur. J. Org. Chem. 2012, 3670–3676
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3673

J. F. Cívicos, D. A. Alonso, C. Nájera
FULL PAPER
fluoroborate afforded pyridines 4k and 4l in 65 and 88% 3b, and 4a with yields in the same range as those obtained
yield, respectively (Table 4, entries 12 and 13).
in the stepwise process.
Because the synthesis of imidazolesulfonates typically
Within a bifunctional starting material, orthogonal reac-
proceeded quantitatively and with minimal byproduct for- tivity allows the chemoselective targeting of one of the two
mation, we decided to carry out a one-pot sulfonylation/ reactive centers, both of which are capable of undergoing
Suzuki cross-coupling sequence employing 1-naphthol as the same chemical transformation. In Suzuki cross-coupling
starting material (Scheme 2). The in situ activation of 1- chemistry, the reactivity of either the electrophilic sites or
naphthol was performed by reaction with 1,1Ј-sufonyldi- the boron reagents can be modulated to carry out orthogo-
[
32,33]
imidazole in tetrahydrofuran (THF) at room temperature nal functionalization.
by using cesium carbonate as base. Once naphthalen-1-yl orthogonal reaction strategies have been reported that take
H-imidazole-1-sulfonate (2ae) was formed (reaction moni- advantage of the differences in bond enthalpies of the C–
With respect to the electrophile,
1
tored by TLC), the one-pot cross-coupling with a range of I, C–Br, C–Cl, and C–O bonds. The reactivity differences
aryl- and styrylboronic acids and potassium trifluoro- between the C–O imidazolesulfonate bond and the C–Br
borates was carried out as depicted in Scheme 2. Both one- and C–Cl bonds facilitated the microwave-promoted or-
pot sulfonylation/arylation and sulfonylation/alkenylation thogonal cross-coupling with arylboronic acids of the halo-
reactions afforded the corresponding coupled products 3a, containing bifunctional compounds 2me and 2ne in a highly
[
34]
chemoselective fashion (Scheme 3).
Thus, 1,1Ј-biphenyl-
4-yl 1H-imidazole-1-sulfonate (3o), obtained from 2me by a
1b-catalyzed coupling with phenylboronic acid through C–
Br activation, was subsequently submitted to the 1a-cata-
lyzed Suzuki coupling with 4-tolylboronic acid under aque-
ous conditions to afford 4-methyl-1,1Ј:4Ј,1ЈЈ-terphenyl (5)
in 84% overall isolated yield (Scheme 3). On the other
hand, 5 was also synthesized from 4-chlorophenyl 1H-imid-
azole-1-sulfonate (2ne) in 57% overall solated yield, by ini-
tial Suzuki coupling with phenylboronic acid followed by
coupling with 4-tolylboronic acid catalyzed by palladacycle
1
b (0.1 mol-% Pd) in the presence of [HP(tBu) ]BF
3 4
[
35]
(0.2 mol-%) in N,N-dimethylformamide (DMF).
Conclusions
We have disclosed a general, phosphane-free oxime–pal-
ladacycle-catalyzed Suzuki cross-coupling reaction of elec-
Scheme 2. One-pot sulfonylation/cross-coupling sequence. Isolated
yield for the stepwise process given in parentheses.
Scheme 3. Orthogonal Suzuki–Miyaura cross-coupling of halogen-containing aryl imidazolesulfonates.
674
3
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 3670–3676

Suzuki–Miyaura Arylation and Alkenylation of Aryl Imidazolesulfonates
tron-rich, electron-poor, and sterically hindered aryl imid-
terscience, New York, 2002, vol. 1, p. 1097; c) Z. Rappoport,
The Chemistry of Phenols, Wiley-VCH, Weinheim, 2003.
3] For a review on the transition-metal-catalyzed synthesis of hy-
droxylated arenes, see: D. A. Alonso, C. Nájera, I. P. Pastor,
M. Yus, Chem. Eur. J. 2010, 16, 5274–5284.
azolesulfonates with aryl- and alkenylboronic acids and po-
tassium trifluoroborates under aqueous conditions. The re-
[
action, which can be performed under conventional heating
or microwave irradiation, has been optimized for use with [4] For recent reviews on the use of new C–O electrophiles in cross-
coupling reactions, see: a) D.-G. Yu, B.-J. Li, Z.-J. Shi, Acc.
Chem. Res. 2010, 43, 1486–1495; b) B.-J. Li, D.-G. Yu, C.-L.
Sun, Z.-J. Shi, Chem. Eur. J. 2011, 17, 1728–1759.
only 1 mol-% Pd in bench-stable palladacycles 1. Further-
more, this methodology allows in situ phenol sulfonylation
and one-pot Suzuki arylation and alkenylation. Further-
more, by taking advantage of the different reactivity pat-
[
5] a) W. Scott, G. Crisp, J. K. Stille, J. Am. Chem. Soc. 1984, 106,
4
630–4632; b) Z. Gilson, R. Larock, Chem. Rev. 2006, 106,
terns shown by the ArC–Br, ArC–Cl, and ArC–OSO Im
4644–4680.
2
[
6] For Pd-catalyzed Suzuki coupling of aryl tosylates and aryl
mesylates with boronic acids or potassium trifluoroborates,
see: a) H. N. Nguyen, X. Huang, S. L. Buchwald, J. Am. Chem.
Soc. 2003, 125, 11818–11819; b) B. Bhayana, B. P. Fors, S. L.
Buchwald, Org. Lett. 2009, 11, 3954–3957; c) L. Zhang, T.
Meng, J. Wu, J. Org. Chem. 2007, 72, 9346–9349; d) C. M. So,
C. P. Lau, F. Y. Kwong, Angew. Chem. 2008, 120, 8179; Angew.
Chem. Int. Ed. 2008, 47, 8059–8063; e) W. K. Chow, C. M. So,
C. P. Lau, F. Y. Kwong, J. Org. Chem. 2010, 75, 5109–5112; f)
G. A. Molander, F. Beaumard, T. K. Niethamer, J. Org. Chem.
bonds under the reaction conditions studied, orthogonal
functionalization of bifunctionalized aryl derivatives
through the Suzuki–Miyaura coupling has been demon-
strated.
Experimental Section
Typical Experimental Procedure for the Arylation Coupling under
Microwave Heating: To a 10 mL microwave vessel charged with 2ae
2
011, 76, 8126–8130; g) G. A. Molander, F. Beaumard, Org.
Lett. 2011, 13, 1242–1245.
(
0.027 g, 0.1 mmol), phenylboronic acid (0.018 g, 0.15 mmol),
KOH (0.011 g, 0.2 mmol), TBAB (0.016 g, 0.05 mmol), and catalyst
b (0.00041 g, 1 mol-% Pd), an MeOH/H O mixture (3:1, 2 mL)
[
7] For Ni-catalyzed Suzuki coupling of aryl tosylates and aryl
mesylates with boronic acids, see: a) D. A. Wilson, C. J. Wilson,
B. M. Rosen, V. Percec, Org. Lett. 2008, 10, 4879–4882; b)
G. A. Molander, F. Beaumard, Org. Lett. 2010, 12, 4022–4025;
c) H. Gao, Y. Li, Y.-G. Zhou, F.-S. Han, Y.-J. Lin, Adv. Synth.
Catal. 2011, 353, 309–314; d) C.-H. Xing, J.-R. Lee, Z.-Y. Tang,
J. R. Zheng, Q.-S. Hu, Adv. Synth. Catal. 2011, 353, 2051–2059.
8] For Ni-catalyzed Suzuki coupling of aryl and alkenyl carb-
amates with arylboronic acids, triaryl boroxines, or aryl
boronates, see: a) Z.-Y. Tang, Q.-S. Hu, J. Am. Chem. Soc.
1
2
was added. The vessel was then sealed with a pressure lock, and
the mixture was heated in air at 110 °C by microwave irradiation
(40 W), keeping this temperature in a CEM Discover microwave
reactor for 20 min. After cooling to room temperature, the reaction
mixture was extracted with EtOAc (3ϫ10 mL), and the combined
[
2
organic layers were washed with H O (3ϫ10 mL), dried with
MgSO , and concentrated under reduced pressure. The crude resi-
4
2
004, 126, 3058–3059; b) K. W. Quasdorf, M. Riener, K. V. Pe-
due was purified by flash chromatography (hexane/EtOAc, 3:1) to
obtain pure 3a (0.019 g, 100%).
trova, N. K. Garg, J. Am. Chem. Soc. 2009, 131, 17748–17749;
c) A. Antoft-Finch, T. Blackburn, V. Snieckus, J. Am. Chem.
Soc. 2009, 131, 17750–17752; d) L. Xu, B.-J. Li, Z.-H. Wu, X.-
Y. Lu, B.-T. Guan, B.-Q. Wang, K.-Q. Zhao, Z.-J. Shi, Org.
Lett. 2010, 12, 884–887; e) K. W. Quasdorf, A. Antoft-Finch,
P. Liu, A. L. Silberstein, A. Komaromi, T. Blackburn, S. D.
Ramgren, K. H. Houk, V. Snieckus, N. K. Garg, J. Am. Chem.
Soc. 2011, 133, 6352–6363; f) P. Leowanawat, N. Zhang, V.
Percec, J. Org. Chem. 2012, 77, 1018–1025.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures for the synthesis of compounds 2
and for cross-coupling reactions as well as spectroscopic data for
all the synthesized products.
Acknowledgments
Financial support from the Spanish Ministry (Projects CTQ2007-
[
9] For Ni-catalyzed Suzuki coupling of aryl carboxylates and alk-
enyl acetates with arylboronic acids or triarylboroxines, see: a)
B.-T. Guan, Y. Wang, B.-J. Li, D.-G. Yu, Z.-J. Shi, J. Am.
Chem. Soc. 2008, 130, 14468–14470; b) K. W. Quasdorf, X.
Tian, N. K. Garg, J. Am. Chem. Soc. 2008, 130, 14422–14423;
c) L. J. Gooßen, K. Gooßen, C. Stanciu, Angew. Chem. 2009,
6
2771/BQU, CTQ2010-20387, Consolider INGENIO 2010
CSD2007-00006, and FEDER), from the Generalitat Valenciana
PROMETEO/2009/038), and the University of Alicante is ac-
knowledged.
(
121, 3621; Angew. Chem. Int. Ed. 2009, 48, 3569–3571; d) C.-
L. Sun, Y. Wang, X. Zhou, Z.-H. Wu, B.-J. Li, B.-T. Guan, Z.-
J. Shi, Chem. Eur. J. 2010, 16, 5844–5847.
[
1] a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457–2483;
b) A. Suzuki, J. Organomet. Chem. 1999, 576, 147–168; c) N.
Miyaura, Top. Curr. Chem. 2002, 219, 11–59; d) J. Hassan, M.
Sevignon, C. Gozzi, E. Schulz, M. Lemaire, Chem. Rev. 2002,
[
10] For Pd-catalyzed Suzuki coupling of heteroaryl carboxylates
and alkenyl acetates with arylboronic acids or potassium aryl
trifluoroborates, see: a) W. Li, J. J. Gao, Y. Zhang, W. Tang, H.
Lee, K. R. Fandrick, B. Lu, C. H. Senanayake, Adv. Synth. Ca-
tal. 2011, 353, 1671–1675; b) J. Lindh, J. Sävmarker, P. Nilsson,
P. J. R. Sjöberg, M. Larhed, Chem. Eur. J. 2009, 15, 4630–4636.
11] For Ni-catalyzed Suzuki coupling of aryl methyl ether with ar-
ylboronic acids, see: M. Tobisu, T. Shimasaki, N. Chatani, An-
gew. Chem. 2008, 120, 4944; Angew. Chem. Int. Ed. 2008, 47,
1
02, 1359–1469; e) S. Kotha, K. Lahiri, D. Kashinath, Tetrahe-
dron 2002, 58, 9633–9695; f) A. F. Littke, G. C. Fu, Angew.
Chem. 2002, 114, 4350; Angew. Chem. Int. Ed. 2002, 41, 4176–
[
4
2
211; g) F. Bellina, A. Carpita, R. Rossi, Synthesis 2004, 2419–
440; h) Metal-Catalyzed Cross-Coupling Reactions, vol. 2
(
2
Eds.: A. de Meijere, F. Diederich), Wiley-VCH, Weinheim,
004; i) U. Christmann, R. Vilar, Angew. Chem. 2005, 117, 370;
4866–4869.
Angew. Chem. Int. Ed. 2005, 44, 366–374; j) F. Alonso, I. P.
Beletskaya, M. Yus, Tetrahedron 2008, 64, 3047–3101; k) Mod-
ern Arylation Methods (Ed.: L. Ackermann), Wiley-VCH,
Weinheim, 2009.
[12] For Pd-catalyzed Suzuki coupling of arylphosphonium salts
with arylboronic acids, see: a) F.-A. Kang, Z. Sui, W. V. Mur-
ray, J. Am. Chem. Soc. 2008, 130, 11300–13302; b) F.-A. Kang,
Z. Sui, W. V. Murray, Eur. J. Org. Chem. 2009, 461–479.
[
2] a) J. H. P. Tyman, Synthetic and Natural Phenols, Elsevier, New [13] For Ni-catalyzed Suzuki coupling of arylphosphonium salts
York, 1996; b) J. F. Hartwig in Handbook of Organopalladium
Chemistry for Organic Synthesis (Ed.: E.-I. Negishi), Wiley-In-
with arylboronic acids, see: G.-J. Chen, J. Huang, L.-X. Gao,
F.-S. Han, Chem. Eur. J. 2011, 17, 4038–4042.
Eur. J. Org. Chem. 2012, 3670–3676
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3675

J. F. Cívicos, D. A. Alonso, C. Nájera
FULL PAPER
[
[
[
14] For Ni-catalyzed Suzuki coupling of arylphosphoramides with
arylboronic acids, see: Y.-L. Zhao, Y. Li, Y. Li, L.-X. Gao, F.-
S. Han, Chem. Eur. J. 2010, 16, 4991–4994.
A. K. Singh, Chem. Commun. 2010, 46, 5954–5956; b) G.-R.
Peh, E. A. B. Kantchev, J.-C. Er, J. Y. Ying, Chem. Eur. J. 2010,
16, 4010–4017; c) E. M. Beccalli, E. Borsini, S. Brenna, S.
Galli, M. Rigamonti, G. Broggini, Chem. Eur. J. 2010, 16,
15] For Ni-catalyzed Suzuki coupling of aryl phosphates with aryl-
boronic acids, see: H. Chen, Z. Huang, X. Hu, G. Tang, P. Xu,
Y. Zhao, C.-H. Cheng, J. Org. Chem. 2011, 76, 2338–2344.
16] For Pd-catalyzed Suzuki coupling of aryl phosphates with aryl-
boronic acids, see: H. Fuwa, M. Sasaki, J. Org. Chem. 2009,
1670–1678; d) L. Wang, X. Cui, J. Li, Y. Wu, Z. Zhu, Y. Wu,
Eur. J. Org. Chem. 2012, 595–603.
[
25] For a recent review on cross-coupling and Heck reactions by
using water as solvent, see: D. A. Alonso, C. Nájera, Water in
Organic Synthesis in Science of Synthesis (Ed.: S. Kobayashi),
George Thieme Verlag KG, Stuttgart, 2012, vol. 2011/7, p. 535.
26] J. F. Cívicos, M. Gholinejad, D. A. Alonso, C. Nájera, Chem.
Lett. 2011, 40, 907–909.
74, 212–221.
[
17] For Ni-catalyzed Suzuki coupling of aryl borates, see: D.-G.
Yu, Z.-J. Shi, Angew. Chem. Int. Ed. 2011, 50, 7097–7100.
18] For Ni-catalyzed Suzuki coupling of aryl sulfamates with aryl-
boronic acids or aryl boronates, see: a) T. K. Macklin, V.
Snieckus, Org. Lett. 2005, 7, 2519–2522; b) P. Leowanawat, N.
Zhang, A.-M. Resmerita, B. M. Rosen, V. Percec, J. Org. Chem.
[
[
[
27] For a Ni-catalyzed Suzuki cross-coupling of aryl carbamates
and sulfamates by using microwave heating, see: M. Baghban-
zadeh, C. Pilger, C. O. Kappe, J. Org. Chem. 2011, 76, 1507–
1510.
2011, 76, 9946–9955.
[28] Catalyst 1a has been shown to be very effective for cross-cou-
[23]
[
19] J. Albaneze-Walker, R. Raju, J. A. Vance, A. J. Goodman,
M. R. Reeder, J. Liao, M. T. Maust, P. A. Irish, P. Espino,
D. R. Andrews, Org. Lett. 2009, 11, 1463–1466.
pling and Heck reactions under aqueous conditions; see ref.
[29] For an interesting comparative study on the Ni-catalyzed cross-
coupling of different aryl C–O electrophiles with aryl neopent-
ylglycolboronates, see ref.[
8f]
[20] For the use of aryl imidazolesulfonates in other cross-coupling
reactions, see: a) Y. Luo, J. Wu, Organometallics 2009, 28,
[30] D. Goubet, P. Meric, J.-R. Dormoy, P. Moreau, J. Org. Chem.
1999, 64, 4516–4518.
6823–6826; b) S. J. Shirbin, B. A. Boughhton, S. C. Zammit,
S. D. Zanatta, S. M. Marcuccio, C. A. Hutton, S. J. Williams,
Tetrahedron Lett. 2010, 51, 2971–2974; c) L. Ackermann, S.
Barfüesser, J. Pospech, Org. Lett. 2010, 12, 724–726.
[31] For a recent 1b-catalyzed Suzuki alkenylation of a wide range
of organic chlorides with alkenylboronic acids or potassium
alkenyltrifluoroborates under microwave irradiation conditions
in DMF, see: J. F. Cívicos, D. A. Alonso, C. Nájera, Adv. Synth.
Catal. 2011, 353, 1683–1687.
[32] M. Tobisu, N. Chatani, Angew. Chem. 2009, 121, 3617; Angew.
Chem. Int. Ed. 2009, 48, 3565–3568.
[
21] Very few examples, usually when potassium trifluoroborates
are cross-coupled with phenol derivatives, have been reported
by using aqueous conditions; see, for instance refs.[
6f,6g,7b,12a]
[
22] Palladacycles: Synthesis Characterization and Applications
(Eds.: J. Dupont, M. Pfeffer), Wiley-VCH, Weinheim, 2008.
[33] For a recent review on the Suzuki couplings of ethane and
arene derivatives bearing two or more electrophilic sites, see: R.
Rossi, F. Bellina, M. Lessi, Tetrahedron 2011, 67, 6969–7025.
[34] For a Pd-catalyzed Suzuki cross-coupling of 2-bromo- and 2-
[
23] For recent reviews on the use of oxime–palladacycles as precat-
alysts in cross-coupling reactions, see: a) E. Alacid, D. A.
Alonso, L. Botella, C. Nájera, M. C. Pacheco, Chem. Rec.
[
18a]
2
006, 6, 117–132; b) D. A. Alonso, C. Nájera, Chem. Soc. Rev.
iodo-O-phenylsulfamates with aryl boronic acids, see ref.
2
010, 39, 2891–2902.
[35] D. A. Alonso, J. F. Cívicos, C. Nájera, Synlett 2009, 3011–3015.
[
24] For recent examples of Suzuki cross-couplings by using pallada-
Received: March 22, 2012
cycles as precatalysts, see: a) G. K. Rao, A. Kumar, J. Ahmedz,
Published Online: May 22, 2012
3676
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 3670–3676