Polyionic heterogeneous phenylating agent for base-free Suzuki-Miyaura coupling reaction

Article abstract of DOI:10.1055/s-2008-1000874

A new polyionic resin-bound tetraphenylborate has been prepared, which can serve as efficient phenylating agent in Pd-catalyzed Suzuki-Miyaura (SM) coupling with aryl halides in the absence of any base. The conditions are mild, operationally simple and the polyionic resin can be recharged and reused for several runs. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1000874

LETTER
255
Polyionic Heterogeneous Phenylating Agent for Base-Free Suzuki–Miyaura
Coupling Reaction
P
B
olyionic Heterog
a
eneous Ph
s
e
nylating
u
A
gent for
S
u
d
z
uki–Miyaur
e
a
Couplin gb Basu,* Sajal Das, Sekhar Kundu, Bablee Mandal
Department of Chemistry, North Bengal University, Darjeeling 734013, India
E-mail: basu_nbu@hotmail.com
Received 26 July 2007
ron species.9,10 Lobrégat et al. showed that arylboronic
Abstract: A new polyionic resin-bound tetraphenylborate has been
prepared, which can serve as efficient phenylating agent in Pd-cat-
alyzed Suzuki–Miyaura (SM) coupling with aryl halides in the ab-
acid may be trapped by an ammonium hydroxide form
®
Dowex ion-exchange resin and the resulting species can
sence of any base. The conditions are mild, operationally simple be used for macroheterocyclization under SM condi-
1
1
and the polyionic resin can be recharged and reused for several runs. tions. In connection with our interest in the development
of ionic resin-bound reagents and/or catalysts,12 we
Key words: polyionic resins, tetraphenylborate, Suzuki–Miyaura
coupling, base-free conditions, biphenyls
sought to develop an ion-exchange resin-supported borate
species as a heterogeneous phenylating agent. In this arti-
cle, we report the preparation of polyionic resin-bound
tetraphenylborate from commercially available anion-ex-
change resins and its preliminary evaluation in SM cou-
pling reactions.
The palladium-catalyzed Suzuki–Miyaura (SM) coupling
reaction of aryl halides with arylboronic acids and esters
has been established as a robust synthetic protocol for the
1
®
preparation of biaryl compounds. The reaction has been Our initial studies began with Amberlite (chloride form)
applied to many areas, including natural product synthe- ion-exchange resins, which were exchanged with tet-
1
c,2
–
sis. Besides the coupling partners, the reaction typical- raphenylborate anion (Ph B ) by continuous rinsing with
4
ly requires Pd catalysts, preferably as complexes with an aqueous solution of NaBPh until the washings gave
4
suitable ligands and a base. In the past few years, great ad- negative response to chloride anion (monitored with
vances have been made in developing active and efficient AgNO solution followed by addition of aqueous ammo-
3
catalysts by modifying traditional ligands and discovering nia). The resin beads were then washed successively with
new ones. Among the variations of the catalyst and the water (to make it free from sodium ions), acetone and fi-
3
base, Leadbeater et al. reported SM coupling reactions nally dried under vacuum for several hours to afford the
3
c
–
using very low levels of Pd (50 ppb), believed to be de- Amberlite resin (Ph B form). Loading of the borate anion
4
livered within the sodium carbonate base, while Yan and was determined by differential weighing between the
co-workers have recently reported base-free SM reaction quantities of the resin (chloride form) initially taken and
using hypervalent iodonium aryl salts instead of aryl ha- recovered after several washings with aqueous solution of
4
13
lides. Besides arylboronic acids and boronate esters, tet- NaBPh , water and drying. This was used directly for the
4
raphenylborates and related borates species being more SM coupling with 3-iodotoluene in the presence of
stable and water resistant, have also been used as arylating Pd(OAc) (2 mol%) and Na CO (1 equiv) and the corre-
2
2
3
5
agents in SM cross-coupling reactions. In view of its ver- sponding unsymmetrical biphenyl was isolated in 90%
satility, the development of new variants of the organobo- yield (Scheme 1, conditions a). Similar coupling of 3-io-
ron species, the catalyst and the base in the SM coupling dotoluene and NaBPh in the presence of Na CO afford-
4
2
3
reaction and the optimization of the process have re- ed only 43% yield of the coupled product (Scheme 1,
mained challenging areas of research.
conditions b). However, on increasing the quantity of
NaBPh in 3-iodotoluene–NaBPh (1:2.5), the resulting
The concept of a resin-capture-release technique generat-
ing the polymer-bound reactive species has been estab-
lished as a potential method for several organic
4
4
coupled product could be isolated in 88% yield
Scheme 1, conditions c). A further interesting observa-
(
6
tion was that the yield of the coupled product was not in-
fluenced by the absence of base (Scheme 1, conditions d
and e). Such base-free conditions for SM reactions offer
significant practical advantages and have not previously
been reported with the organoborate ion immobilized onto
polymers.
transformations. Although polymer-bound boronic acids
7
8
were reported as early as 1976, Frenette and Friesen, in
994, investigated the utility of the SM coupling reaction
1
on a solid support for combinatorial chemistry. A variety
of techniques to immobilize different components of SM
reactions on macroporous solids clearly revealed the lack
of application of polyionic resins soaked with organobo- The common mechanism of SM coupling reactions (i.e.,
sequential oxidative addition, transmetalation, and reduc-
tive elimination) includes a base, which is believed to be
SYNLETT 2008, No. 2, pp 0255–0259
Advanced online publication: 21.12.2008
DOI: 10.1055/s-2008-1000874; Art ID: D23207ST
x
x.
x
x.
2
0
0
8
involved in several steps of the catalytic cycle, most nota-
1c,14
bly the transmetalation process.
While the weak carb-
©
Georg Thieme Verlag Stuttgart · New York

2
56
B. Basu et al.
LETTER
+
–
NR3 BPh4
Me
I
II
Me
Ph
Pd(OAc)2 (2 mol%)
5 °C, 2 h
+
or
8
NaBPh4
III
I
conditions:
(
(
(
(
(
a) I/II/Na2CO3 = 1:1 g/mmol:1; 90%
b) I/III/Na2CO3 = 1:1:1; 43%
c) I/III/Na2CO3 = 1:2.5:1; 88%
d) I/III = 1:2.5; 88%
e) I/II = 1:1 g/mmol; 96%
Scheme 1
anionic character of the organic moiety attached to boron Efficient coupling between 3-iodotoluene and the immo-
in triorganoboranes requires base to assist in the transmet- bilized tetraphenylborate under base-free conditions
alation process, the corresponding ‘ate’ species is capable prompted us to develop a general method for the SM reac-
1
e,15–19
20
of accelerating the transmetalation.
The transmeta- tion. A variety of aryl iodides or bromides bearing elec-
lation process releases triphenylborane, which is water- tron-donating or electron-withdrawing groups as well as
sensitive and may be hydrolyzed during the workup, pro- heteroaryl halides underwent SM couplings in either
ducing phenyl boronic acid. Indeed, we were able to iso- DMF or water at 80–90 °C, resulting in the formation of
late and characterize phenylboronic acid from the reaction the desired products in excellent yields (Table 1). In order
mixture. It may therefore be proposed that the resin-sup- to broaden the scope of the base-free reaction conditions,
ported tetraphenylborate not only serves as an efficient we also examined bis- or trisaryl halides (Table 1, entries
phenylating agent but also acts as a suitable nucleophile 16–20). In all cases, the desired adducts were isolated in
requisite in the transmetalation process.
good to excellent yields.
Table 1 Suzuki–Miyaura Couplings Using Amberlite Resins (Tetraphenylborate Form)
Entry
1
Aromatic halidea
Temp (°C)
80
Time (h)
2
Productb
Yield (%)c
91 (91)
Me
Me
I
Me
Me
2
3
85
85
2
3
96 (95)
89
I
MeO
MeO
I
OMe
OMe
I
4
5
6
90
80
80
4
76
2.5
2
95 (92)
95
Cl
Cl
I
Cl
Cl
I
F
F
7
8
9
90
85
80
3
4
6
88
91
71
I
I
CF3
CF3
I
Synlett 2008, No. 2, 255–259 © Thieme Stuttgart · New York

LETTER
Polyionic Heterogeneous Phenylating Agent for Suzuki–Miyaura Coupling
257
Table 1 Suzuki–Miyaura Couplings Using Amberlite Resins (Tetraphenylborate Form) (continued)
Entry
Aromatic halidea
Temp (°C)
80
Time (h)
2
Productb
Yield (%)c
Cl
Cl
1
0
86 (88)
Br
1
1
1
2
80
80
3
3
92
83
MeOC
EtO2C
Br
Br
MeOC
EtO2C
1
1
3
80
85
3
6
90
I
S
S
4d
80 (75)
N
N
Br
N
Br
1
1
5d
80
90
4
3
97
84
N
6d
N
Br
N
Br
Br
Br
1
7
90
4
77
1
1
8
9
80
85
3
3
78 (85)
87
I
I
Br
Br
OH
OH
Br
Br
Br
2
0
90
8
58
2
2
1e
2e
90
85
5
5
(88)
(95)
MeOC
O2N
Cl
MeOC
O2N
Cl
a
b
c
d
e
Reaction conditions: aryl halide (1 mmol), resin-TPB (1 g), and Pd(OAc) (2 mol%) in DMF or H O.
All compounds were characterized by known mp, IR, H NMR and C NMR spectral data.
2
2
1
13
Yields in parentheses represent reactions carried out in H O.
2
Pd (dba) (1.5 mol%) was used instead of Pd(OAc) .
2
3
2
TBAB (1 equiv) and Na CO (1 equiv) were required.
2
3
Synlett 2008, No. 2, 255–259 © Thieme Stuttgart · New York

2
58
B. Basu et al.
LETTER
Typical problems encountered during SM coupling reac-
tions using the base, such as saponification of esters or al-
dol-type condensations of carbonyl compounds limit the
functionality that can be present in the aryl moiety. To ex-
tend the scope of this reaction condition, couplings of aryl
(3) (a) Leadbeater, N. E.; Marco, M. Angew. Chem. Int. Ed.
003, 42, 1407. (b) Leadbeater, N. E.; Marco, M. J. Org.
2
Chem. 2003, 68, 5660. (c) Arvela, R. K.; Leadbeater, N. E.;
Sangi, M. S.; Williams, V. A.; Granados, P.; Singer, R. D.
J. Org. Chem. 2005, 70, 161.
(
4) (a) Yan, J.; Hu, W.; Zhou, W. Synth. Commun. 2006, 36,
2097. (b) Yan, J.; Zhou, Z.; Zhu, M. Synth. Commun. 2006,
36, 1495.
bromides bearing ketone (COMe), ester (CO Et) and OH
2
groups were studied (Table 1, entries 11, 12, 20 and 21).
The results from these reactions are listed in Table 1.
(5) (a) Molander, G. A.; Rivero, M. R. Org. Lett. 2002, 4, 107.
b) Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68,
302. (c) Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J.
(
4
Activated aryl chlorides are known to undergo SM cou-
2
1
pling reactions. Using the immobilized borate we per-
Tetrahedron 2001, 57, 9925. (d) Kabalka, G. W.; Al-
Masum, M. Tetrahedron Lett. 2005, 46, 6329.
formed base-free couplings with activated aryl chlorides
successfully (Table 1, entries 21 and 22) in presence of
(6) (a) Kirschning, A.; Monenschein, H.; Wittenberg, R. Chem.
Eur. J. 2000, 6, 4445. (b) Keay, J. G.; Scriven, E. F. V.
Chem. Ind. (London) 1994, 53, 339. (c) Khound, S.; Das, P.
J. Tetrahedron 1997, 53, 9749.
(7) Farrall, M. J.; Fréchet, J. M. J. J. Org. Chem. 1976, 41, 3877.
(8) Frenette, R.; Friesen, R. W. Tetrahedron Lett. 1994, 35,
one equivalent of tetrabutylammonium salts (TBAB).22
Finally, we considered recycling the recovered resin in
SM coupling reactions. The formation of the desired ad-
duct was obtained in lower yield than in the first run,
which might be due to poor availability of the tetraphen-
ylborate counter anions. However, recharging the resin
and recycling the reaction was successfully achieved for
9177.
(9) For some recent examples, see: (a) Roller, S.; Turk, H.;
Stumbe, J.-F.; Rapp, W.; Haag, R. J. Comb. Chem. 2006, 8,
350. (b) Zheng, Y.; Stevens, P. D.; Gao, Y. J. Org. Chem.
2
3
five runs. Conducting reactions in aqueous medium can
be advantageous, particularly for large-scale industrial ap-
plications, as a result of ease of purification as well as the
environmental friendliness of water. The newly devel-
oped polyionic resins are equally effective in the aqueous-
medium SM reaction thereby offering greater scope for its
applications.
2
006, 71, 537. (c) Nielsen, T. E.; Quement, S. L.; Meldal,
M. Tetrahedron Lett. 2005, 46, 7959. (d) Brown, J. F.;
Krajnc, P.; Cameron, N. R. Ind. Eng. Chem. Res. 2005, 44,
8565. (e) Bork, J. T.; Lee, J. W.; Chang, Y.-T. Tetrahedron
Lett. 2003, 44, 6141. (f) Wade, J. V.; Krueger, C. A.
J. Comb. Chem. 2003, 5, 267. (g) Hebel, A.; Haag, R.
J. Org. Chem. 2002, 67, 9452.
(
10) As compared to other polymeric frameworks, examples
using solid polyionic resins to immobilize organoboron
species for use in SM couplings are limited. A few examples
on the immobilization of arylboronic acids are: (a) Wulff,
G.; Schmidt, H.; Witt, H.; Zentel, R. Angew. Chem., Int. Ed.
Engl. 1994, 33, 188. (b) Guiles, J. W.; Johnson, S. G.;
Murray, W. V. J. Org. Chem. 1996, 61, 5169. (c) Piettre, S.
R.; Baltzer, S. Tetrahedron Lett. 1997, 38, 1197. (d) Kell,
R. J.; Hodge, P.; Nisar, M.; Williams, R. T. J. Chem. Soc.,
Perkin Trans. 1 2001, 3403.
11) Lobrégat, V.; Alcaraz, G.; Bienayme, H.; Vaultier, M.
Chem. Commun. 2001, 817.
12) (a) Basu, B.; Das, S.; Das, P.; Nanda, A. K. Tetrahedron
Lett. 2005, 46, 8591. (b) Basu, B.; Das, P.; Das, S. Mol.
Diversity 2005, 9, 259. (c) Basu, B.; Bhuiyan, M. M. H.;
Das, P.; Hossain, I. Tetrahedron Lett. 2003, 44, 8931.
In summary, we have shown that polyionic resins may be
used for immobilizing tetraphenylborate as well as for ful-
filling the function of a base and the resulting species are
potential phenylating agents in the SM cross-coupling.
The reaction conditions offer an efficient and general
method for base-free SM cross-coupling reactions leading
to the formation of biaryls. Easy isolation of the desired
coupled products in high yields along with base- and
ligand-free conditions offer distinct advantages over the
direct use of corresponding alkali metal salts or phenylbo-
ronic acid. Further exploration of the methodology is un-
derway in this laboratory.
(
(
®
(
13) Amberlite IRA-900 resin (chloride form; 2.50 g) was
Acknowledgment
stirred with aq NaBPh (1.73 g) until complete exchange as
judged by Cl loss (AgNO ). The exchanged resin was
washed with H O, acetone and dried to give the tetra-
phenylborate-form resin (3.92 g). The mass difference
between product and starting materials (ca. 310 mg) was
comparable with the calculated difference (296 mg). The
resulting borate-bound resin thus contained a 1.14 mmol g
loading of the borate ions and was used directly in the SM
coupling reactions.
4
–
We are grateful to the Department of Science & Technology, New
Delhi for financial support (Grant No. SR/S1/OC–49/2006). S.D.
and B.M. thank CSIR, New Delhi for awarding senior research fel-
lowships.
3
2
–
1
References and Notes
(
1) For reviews, see: (a) Hassan, J.; Sevignon, M.; Gozzi, C.;
(
(
14) Suzuki, A. Chem. Commun. 2005, 4759.
15) (a) Miyaura, N.; Ishiyama, T.; Ishikawa, M.; Suzuki, A.
Tetrahedron Lett. 1986, 27, 6369. (b) Miyaura, N.;
Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh, M.; Suzuki,
A. J. Am. Chem. Soc. 1989, 111, 314.
16) Gropen, O.; Haaland, A. Acta. Chem. Scand. 1973, 27, 521.
17) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am.
Chem. Soc. 1985, 107, 972.
Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359.
(
b) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002,
58, 9633. (c) Chemler, S. R.; Trauner, D.; Danishefsky, S. J.
Angew. Chem. Int. Ed. 2001, 40, 4544. (d) Suzuki, A.
J. Organomet. Chem. 1999, 576, 147. (e) Miyaura, N.;
Suzuki, A. Chem. Rev. 1995, 95, 2457. (f) Miyaura, N. Top.
Curr. Chem. 2002, 219, 11. (g) Bellina, F.; Carpita, A.;
Rossi, R. Synthesis 2004, 2419.
(
(
(
18) Darses, S.; Genet, J. P.; Brayer, J. L. Tetrahedron Lett. 1997,
(
2) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem. Int.
Ed. 2005, 44, 4442.
37, 4393.
Synlett 2008, No. 2, 255–259 © Thieme Stuttgart · New York

LETTER
Polyionic Heterogeneous Phenylating Agent for Suzuki–Miyaura Coupling
259
–
1 1
(
19) (a) Fürstner, A.; Seidel, G. Tetrahedron 1995, 51, 11165.
b) Smith, G. B.; Denezy, G. C.; Hughes, D. L.; King, A. O.;
Verhoeven, T. R. J. Org. Chem. 1994, 59, 8151.
c) Aliprantis, A. O.; Canary, J. W. J. Am. Chem. Soc. 1994,
16, 6985. (d) Wright, S. W.; Hageman, D. L.; McClure, L.
2900, 1604 cm . H NMR (300 MHz, CDCl ): d = 7.84–
3
(
7.87 (m, 2 H), 7.56–7.71 (m, 6 H), 7.42 (d, J = 7.2 Hz, 1 H),
1
3
2.67 (s, 3 H). C NMR (75 MHz, CDCl ): d = 141.3, 141.2,
3
(
1
138.2, 128.7, 128.6, 127.94, 127.89, 127.2, 127.1, 124.2,
21.5.
D. J. Org. Chem. 1994, 59, 6095.
20) Representative Procedure for Suzuki–Miyaura
(21) For a review, see: Littke, A. F.; Fu, G. C. Angew. Chem. Int.
Ed. 2002, 41, 4176.
(
Reaction: A mixture of 3-iodotoluene (218 mg, 1 mmol),
(22) (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem.
Soc. 1998, 120, 9722. (b) Botella, L.; Nájera, C. Angew.
Chem. Int. Ed. 2002, 41, 179.
–
Amberlite resin (Ph B form) (1 g, 1.14 mmol) and
4
Pd(OAc) (4.5 mg, 2 mol%) was taken in DMF (2 mL) and
2
heated in an oil bath at 85 °C for 2 h. After cooling, the
(23) After the first run, the resin beads were filtered off, washed
reaction mixture was diluted with H O (5 mL) and the resin
with MeOH, then with H O and finally rinsed again with aq
2
2
was filtered off. The filtrate was extracted with Et O (3 × 15
NaBPh solution. The resulting borate-bound resin could be
2
4
mL) and the combined organic layers were dried over anhyd
Na SO . Removal of the solvent left an oily residue, which
reused for the SM reaction. Employing the recovered and
recharged resin (tetraphenylborate form) for SM coupling
with 3-iodotoluene (1 mmol scale), provided the desired
biaryl in 95% yield. The three subsequent runs gave the
biaryl in 92%, 92% and 88% yields.
2
4
was passed through a short column of silica gel (60–120
mesh) eluting with light petroleum to afford 3-phenyltoluene
as a colorless liquid (161 mg, yield 96%). IR (neat): 3031,
Synlett 2008, No. 2, 255–259 © Thieme Stuttgart · New York

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