Base-free oxidative homocoupling of arylboronic esters

Article abstract of DOI:10.1016/S0040-4039(03)00023-6

Base-free oxidative homocoupling reaction of arylboronic esters has been found to proceed using a catalytic amount of a palladium-1,3-bis(diphenylphosphino)propane (DPPP) complex under an oxygen atmosphere, affording a variety of biaryls in modest to excellent yields. Even arylboronic esters bearing a base-sensitive functional group are applicable to the reaction.

Full text of DOI:10.1016/S0040-4039(03)00023-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1541–1544
Base-free oxidative homocoupling of arylboronic esters
Hiroto Yoshida,* Yasuhito Yamaryo, Joji Ohshita and Atsutaka Kunai
Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University, Higashi-Hiroshima 739-8527, Japan
Received 7 December 2002; revised 27 December 2002; accepted 7 January 2003
Abstract—Base-free oxidative homocoupling reaction of arylboronic esters has been found to proceed using a catalytic amount of
a palladium–1,3-bis(diphenylphosphino)propane (DPPP) complex under an oxygen atmosphere, affording a variety of biaryls in
modest to excellent yields. Even arylboronic esters bearing a base-sensitive functional group are applicable to the reaction. © 2003
Elsevier Science Ltd. All rights reserved.
Palladium-catalyzed cross-coupling of organic halides
(pseudohalides) with organoboron compounds, i.e.
Suzuki–Miyaura coupling, has proven to be one of the
most powerful and popular carbon–carbon bond form-
ing reactions, widely used for the synthesis of valuable
organic compounds such as pharmaceuticals and func-
tionality materials.1 Similarly, palladium-catalyzed
homocoupling of organoboron compounds, although
less familiar, is also a potential method for carbon–car-
bon bond formation, where symmetrical organic com-
pounds are produced straightforwardly.2 In these
reactions, however, addition of a stoichiometric or
excess amount of bases is indispensable for smooth
transformation, which precludes the application of
base-sensitive compounds to the coupling process, and
the production of an equivalent amount of waste salts
is unavoidable besides. Consequently, development of
palladium-catalyzed coupling reactions of organoboron
compounds without added bases has been a challenging
and urgent issue.3,4 We report herein the base-free
oxidative homocoupling of arylboronic esters, which is
product should result from the oxidation of the C–B
bond of 3 with hydrogen peroxide6 arising from boron
peroxide (vide infra) and water, which would be gener-
ated in situ from 3 via tri(p-tolyl)boroxine production.7
Therefore, we expected that the employment of an
organoboronic ester in lieu of an organoboronic acid
would eliminate the in situ-generation of water to lead
to the exclusive formation of the desired homocoupling
product. Thus, when the cyclic ester of 3, 2-(p-tolyl)-
1,3,2-dioxaborinane (1a), was treated under the above
reaction conditions, 2a was actually formed in 99%
yield (Entry 2). The use of tetrakis(triphenyl-
phosphine)palladium or a ligandless palladium salt was
less effective than a palladium–DPPP complex and gave
an 81% or 90% yield of 2a, respectively (Entries 3 and
4). The reaction did not proceed at all under a strictly
prepared argon atmosphere, implying that molecular
oxygen was indispensable for the homocoupling (Entry
5).
efficiently
catalyzed
by
a
palladium–1,3-bis-
(diphenylphosphino)propane (DPPP) complex under an
oxygen atmosphere.5
We first carried out the reaction of p-tolylboronic acid
(3) in dimethylsulfoxide (DMSO) at 80°C without any
added bases using a palladium–DPPP complex as the
catalyst under an oxygen atmosphere and found that
the homocoupling product, 4,4%-dimethylbiphenyl (2a),
was produced in 75% yield along with an 11% yield of
p-cresol (4) (Scheme 1, Entry 1 of Table 1). This side
Keywords: biaryls; boron; homocoupling; oxygen; palladium.
* Corresponding author. Tel.: +81-824-24-7724; fax: +81-824-24-5494;
e-mail: yhiroto@hiroshima-u.ac.jp
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(03)00023-6

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H. Yoshida et al. / Tetrahedron Letters 44 (2003) 1541–1544
Table 1. Palladium-catalyzed homocoupling of p-tolylboranesa
Entry
p-Tolylborane
Catalyst
Time (h)
Yield (%)b
Product(s)
1c
2c
3
3
DPPP/Pd(OAc)2
DPPP/Pd(OAc)2
Pd(PPh3)4
Pd(OAc)2
DPPP/Pd(OAc)2
15
26
23
26
38
75(11)d
99
81
90
B1
2a, 4
2a
2a
2a
2a
1a
1a
1a
1a
4
5c,e
a The reaction was carried out in DMSO (1.0 mL) at 80°C using p-tolylborane (0.30 mmol) in the presence of a palladium (8.9 mmol) under an
oxygen atmosphere.
b Isolated yield based on p-tolylborane.
c DPPP/Pd=1.5.
d GC yield of 4.
e Under an argon atmosphere.
Other results of the base-free oxidative homocoupling
of various arylboronic esters 1 are summarized in Table
2. Similarly to the case of 1a, phenylboronic ester (1b)
and arylboronic esters bearing an electron-withdrawing
group (1c and 1d) or an electron-donating group (1e
and 1f) at the para-position afforded the corresponding
homocoupling products in excellent yields (Scheme 2,
Entries 1–6). Furthermore, the reaction of meta-substi-
tuted arylboronic esters (1g–i) took place successfully,
providing a 73%, 90% or 86% yield of biaryls (2g–i),
respectively (Entries 7–9). Naphthylboronic ester 1j also
reacted efficiently to give 2,2%-binaphthyl (2j) in 78%
yield (Entry 10), whereas the reaction of sterically more
congested arylboronic esters 1k and 1l resulted in mod-
erate yields (Entries 11 and 12). It should be stressed
that the present base-free conditions allow the employ-
ment of arylboronic esters with a relatively base-sensi-
tive group (1m and 1n) to the reaction, leading to the
formation of the corresponding homocoupling products
(2m and 2n) in reasonable yields (Entries 13 and 14).
Moreover, the homocoupling was also applicable to a
cross-coupling-active substrate, 4-bromophenylboronic
ester (1o), whose C–Br bond remained intact (Entry
15).
not only bases but also special oxidants, the present
reaction offers a general and environmentally-benign
method for the synthesis of diverse biaryls. Further
studies on details of the mechanism as well as other
Table 2. Pd–DPPP-catalyzed oxidative homocoupling of
arylboronic esters
Although details of the reaction pathway remain
unclear at present, the fact that oxygen readily reacts
with palladium(0) to afford palladium(II) peroxide may
enable us to propose the following catalytic cycle
(Scheme 3).8 Initially, three-membered palladium(II)
peroxide complex 7 is formed by oxidative cyclization
of molecular oxygen with palladium(0) complex 6. Sub-
sequent double transmetalation of an organic moiety in
1 from boron to palladium(II) would occur without an
aid of a base to give diorganopalladium 9 and boron
peroxide 109 through intermediary complex 8, and then
reductive elimination of homocoupling product 2 from
9 follows with regeneration of palladium(0)–DPPP
complex 6.10 Since transmetalation of
a neutral
organoboron compound with an oxygen-bound pallad-
ium(II) complex11 has been reported to be facile pro-
cess, this catalytic cycle rationally explains the overall
results.12,13
In conclusion, we have developed the palladium–DPPP
complex-catalyzed base-free oxidative homocoupling
reaction of arylboronic esters. In view of the disuse of

H. Yoshida et al. / Tetrahedron Letters 44 (2003) 1541–1544
1543
Int. Ed. 2001, 40, 3458; (g) Liebeskind, L. S.; Srogl, J.
Org. Lett. 2002, 4, 979; (h) Kakino, R.; Yasumi, S.;
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Yamamoto, A. Bull. Chem. Soc. Jpn. 2002, 75, 1333.
4. Recently, transition metal-catalyzed addition of
organoboron compounds to unsaturated organic com-
pounds without added base has attracted considerable
attention, see: (a) Sakai, M.; Hayashi, H.; Miyaura, N.
Organometallics 1997, 16, 4229; (b) Sakai, M.; Ueda, M.;
Miyaura, N. Angew. Chem. Int. Ed. 1998, 37, 3279; (c)
Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.;
Miyaura, N. J. Am. Chem. Soc. 1998, 120, 5579; (d)
Hayashi, T.; Senda, T.; Takaya, Y.; Ogasawara, M. J.
Am. Chem. Soc. 1999, 121, 11591; (e) Hayashi, T.; Senda,
T.; Ogasawara, M. J. Am. Chem. Soc. 2000, 122, 10716;
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Commun. 2001, 2688.
Scheme 2.
Scheme 3.
5. There has been only one report on the palladium-cata-
lyzed base-free oxidative homocoupling of organoboronic
acids, however, the low to moderate product yields and
the formation of undesirable side-products seem to
impair its synthetic utility, see: Moreno-Man˜as, M.;
Pe´rez, M.; Pleixats, R. J. Org. Chem. 1996, 61, 2346.
6. Although the reaction of organoboranes with oxygen was
reported to give the corresponding alcohols, no trace of
p-cresol (4) was detected in the reaction of 3 without
using the catalyst. This result would rule out the direct
oxidation pathway with oxygen in the formation of 4.
For the oxidation of trialkylboranes with oxygen, see:
Brown, H. C.; Midland, M. M.; Kabalka, G. W. J. Am.
Chem. Soc. 1971, 93, 1024.
palladium-catalyzed base-free carbon–carbon bond
forming reactions of organoboron compounds are in
progress.
General procedure: A DMSO solution (1.0 mL) of
1,3-bis(diphenylphosphino)propane (5.5 mg, 0.013
mmol) and Pd(OAc)2 (2.0 mg, 8.9 mmol) was degassed
through two freeze-thaw cycles, and the reaction flask
was charged with oxygen. To this solution was added
an arylboronic ester (0.30 mmol) and the resulting
mixture was stirred at 80°C. After the time specified in
Table 2, the mixture was diluted with ether, washed
with water and dried over magnesium sulfate. Evapora-
tion of the solvent followed by silica-gel column chro-
matography (hexane or hexane–ethyl acetate as an
eluent) gave the corresponding product.
7. (a) Lappert, M. F. Chem. Rev. 1956, 56, 959; (b) Evans,
D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett. 1998,
39, 2937.
8. (a) Lyons, J. E. In Oxygen Complexes and Oxygen Acti-
vation by Transition Metals; Martell, A. E.; Sawyer, D.
T., Eds.; Plenum Press: New York, 1988; pp. 233–251; (b)
Stahl, S. S.; Thorman, J. L.; Nelson, R. C.; Kozee, M. A.
J. Am. Chem. Soc. 2001, 123, 7188; (c) Steinhoff, B. A.;
Fix, S. R.; Stahl, S. S. J. Am. Chem. Soc. 2002, 124, 766.
9. Although the ultimate fate of 10 was not identified at
present, boron peroxide should decompose into boronic
acid, its esters, etc. For thermal decomposition of
organoboron peroxides, see: Maslennikov, V. P.; Makin,
G. I.; Alyasov, V. N.; Aleksandrov, Y. A. Zh. Obshch.
Khim. 1973, 43, 1972.
10. In general, in situ reoxidation of a palladium(0) complex
to a palladium(II) complex with molecular oxygen alone
is not an easy process, however, DMSO has been
reported to be an exceptionally efficient solvent for this
purpose: (a) Tsuji, J. Palladium Reagents and Catalysts;
Wiley: Chichester, 1995; Chap. 3; (b) Larock, R. C.;
Hightower, T. R. J. Org. Chem. 1993, 58, 5298; (c) van
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357; (d) van Benthem, R. A. T. M.; Hiemstra, H.; van
Leeuwen, P. W. N. M.; Geus, J. W.; Speckamp, W. N.
Angew. Chem. Int. Ed. Engl. 1995, 34, 457; (e) Larock, R.
C.; Hightower, T. R.; Kraus, G. A.; Hahn, P.; Zheng, D.
Tetrahedron Lett. 1995, 36, 2423; (f) Ro¨nn, M.; Ba¨ckvall,
J. E.; Andersson, P. G. Tetrahedron Lett. 1995, 36, 7749.
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