Chemistry Letters Vol.35, No.2 (2006)
165
was also synthesized in excellent yield (Scheme 2). In this case,
the use of ligand 3 rather than 4 gave better results in the cross-
coupling step.
OTf
a
c
c
2 h
100%
6 h
98%
12 h
99%
X
X
b
2a: X = OH
5: X = OTf
X
b
As shown in Scheme 3, the ‘‘branching’’ of an oligoarene
chain was realized using a mono-protected dihydroxyphenylbor-
onic acid. First, 4-hydroxy-3-methoxyphenylboronic acid was
employed in the cross-coupling step to generate a ‘‘branch’’ point
(step a). Next, the main chain was elongated (steps b and c). The
methyl ether was then cleaved to give the OH group (step d) that
can be elongated (steps b and e). Using this methodology, the
‘‘branch’’ and main chains can be independently extended.
96%
6: X = OH
7: X = OTf
8: X = OH
9: X = OTf
b
99%
99%
c
14 h
96%
OH
10
Scheme 1. Synthesis of an oligoarene with ortho-connection. Con-
ditions: (a) 1a (1.3 equiv.), Pd(OAc)2 (2 mol %), 3 (2.4 mol %), KF
(3.3 equiv.), THF/H2O (4/1), rt. (b) Tf2O (1.2 equiv.), pyridine (1.5
equiv.), CH2Cl2, 0 ꢀC, 20 min. (c) 1a (1.6 equiv.), Pd(OAc)2
(2 mol %), 4 (2.4 mol %), KF (3.3 equiv.), THF/H2O (4/1), rt.
We thank MEXT (Grant-in-Aid for Scientific Research)
for financial support.
References and Notes
1
OTf
X
a
a
a
X
a) J. M. Tour, Chem. Rev. 1996, 96, 537. b) A. J. Berresheim, M.
Muller, K. Mullen, Chem. Rev. 1999, 99, 1747. c) D. J. Hill,
6 h
100%
6 h
100%
6 h
100%
¨
¨
13: X = OH
14: X = OTf
11: X = OH
12: X = OTf
b
98%
b
96%
M. J. Mio, R. B. Prince, T. S. Hughes, J. S. Moore, Chem. Rev.
2001, 101, 3893. d) F. J. M. Hoeben, P. Jonkheijm, E. W. Meijer,
A. P. H. J. Schenning, Chem. Rev. 2005, 105, 1491. e) J.-M.
Lehn, Supramolecular Chemistry: Concepts and Perspectives,
VCH, Weinheim, 1995, Chap. 9. f) N. Sakai, J. Mareda, S.
Matile, Acc. Chem. Res. 2005, 38, 79.
OH
a
X
6 h
99%
15: X = OH
16: X = OTf
17
b
96%
2
3
R. B. Merrifield, J. Am. Chem. Soc. 1963, 85, 2149.
Examples of repetitive oligoarene synthesis: a) W. Cheng, V.
Snieckus, Tetrahedron Lett. 1987, 28, 5097. b) P. Liess, V.
Hensel, A. D. Schluter, Liebigs Ann. 1996, 1037. c) A. J. Blake,
¨
P. A. Cooke, K. J. Doyle, S. Gair, N. S. Simpkins, Tetrahedron
Lett. 1998, 39, 9093. d) P. R. L. Malenfant, L. Groenendaal,
Scheme 2. Synthesis of an oligoarene with meta-connection.
Conditions: (a) 3-hydroxyphenylboronic anhydride (1.3 equiv.),
Pd(OAc)2 (2 mol %), 3 (2.4 mol %), KF (3.3 equiv.), THF/H2O
(4/1), rt. (b) Tf2O (1.2 equiv.), pyridine (1.5 equiv.), CH2Cl2,
0 ꢀC, 20 min.
´
J. M. J. Frechet, J. Am. Chem. Soc. 1998, 120, 10990. e) T.
Kirschbaum, R. Azumi, E. Mena-Osteritz, P. Bauerle, New J.
droxyphenylboronic acid (1b) (Entry 19 vs 20). To summarize,
whereas PCy3 in aqueous DMF may be economically preferable,
ligand 3 or 4 in aqueous THF is the ligand of choice in the cross-
coupling of hydroxyphenylboronic acids or anhydrides.
As shown in Scheme 1, the cross-coupling conditions were
applied to the synthesis of oligoarene backbones, in which a pen-
tamer 10, with benzene rings connected at ortho-position, was
readily synthesized through the rapid cross-coupling–triflation
procedure. Note that, despite the presence of a bulky oligoarene
chain at the ortho-position, the yield of each cross-coupling step
was nearly quantitative, while longer reaction times and larger
amounts of 1a were required as the oligoarene chain increased.
An oligoarene 17 that was connected through the meta-position
¨
Chem. 1999, 241. f) M. W. Read, J. O. Escobedo, D. M. Willis,
P. A. Beck, R. M. Strongin, Org. Lett. 2000, 2, 3201. g) B. P.
Orner, J. T. Ernst, A. D. Hamilton, J. Am. Chem. Soc. 2001,
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H. Lu, A. D. Hamilton, Angew. Chem., Int. Ed. 2002, 41, 278.
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Park, T. Chang, M. Lee, J. Am. Chem. Soc. 2004, 126, 6294. j)
A. L. Kanibolotsky, R. Berridge, P. J. Skabara, I. F. Perepichka,
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13695.
a) N. Miyaura, T. Yanagi, A. Suzuki, Synth. Commun. 1981, 11,
513. b) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457. c) A.
Suzuki, H. C. Brown, Organic Synthesis via Boranes, Vol. 3,
Suzuki Coupling, Aldrich Chemical Company, Milwaukee, 2003.
Hamilton et al. have reported a repetitive three-step strategy
(deprotection–cross-coupling–triflation) using methoxyphenyl-
boronic acids to synthesize substituted p-terphenyls,3h although
the cross-coupling step required high temperature.
H. Gilman, L. Santucci, D. R. Swayampati, R. O. Ranck, J. Am.
Chem. Soc. 1957, 79, 3077. The real aggregation states of the
boronic anhydrides are unclear because of the complexity associ-
ated with the phenolic hydroxy groups.
A. F. Littke, C. Dai, G. C. Fu, J. Am. Chem. Soc. 2000, 122, 4020.
Use of aqueous solvents with fluoride anion: S. W. Wright, D. L.
Hageman, L. D. McClure, J. Org. Chem. 1994, 59, 6095.
In the reaction in DMF/H2O (10/1), the amount of H2O was 3.9
equiv to 1a.
4
5
6
OMe
(HO)2B
OTf
OH
OMe
X
OMe
c
d
a
4 h
96%
98%
2 h
98%
20
18: X = OH
19: X = OTf
b
97%
OH
X
e
4 h
7
8
100%
23
21: X = OH
22: X = OTf
b
99%
9
Scheme 3. Synthesis of a branched oligoarene. Conditions: (a) 4-
hydroxy-3-methoxyphenylboronic acid (1.3 equiv.), Pd(OAc)2
(2 mol %), 4 (2.4 mol %), KF (3.3 equiv.), THF/H2O (4/1), rt.
(b) Tf2O (1.2 equiv.), pyridine (1.5 equiv.), CH2Cl2, 0 ꢀC, 20 min.
(c) Phenylboronic acid (1.3 equiv.), Pd(OAc)2 (2 mol %), 3 (2.4
mol %), KF (3.3 equiv.), THF/H2O (4/1), rt. (d) BBr3 (2.0 equiv.),
CH2Cl2, 0 ꢀC to rt, 2 h. (e) 1b (1.3 equiv.), Pd(OAc)2 (2 mol %), 4
(2.4 mol %), KF (3.3 equiv.), THF/H2O (4/1), rt.
10 H. N. Nguyen, X. Huang, S. L. Buchwald, J. Am. Chem. Soc.
2003, 125, 11818.
11 a) S. D. Walker, T. E. Barder, J. R. Martinelli, S. L. Buchwald,
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