Surface Functionalization of Polyether Dendrimers Using Palladium-Catalyzed Cross-Coupling Reactions

Full text of DOI:10.1021/jo980380v

J . Org. Chem. 1998, 63, 5675-5679
5675
Sch em e 1
Su r fa ce F u n ction a liza tion of P olyeth er
Den d r im er s Usin g P a lla d iu m -Ca ta lyzed
Cr oss-Cou p lin g Rea ction s
L. Groenendaal and J . M. J . Fre´chet*
Department of Chemistry, University of California-Berkeley,
Berkeley, California 94720-1460
Received March 2, 1998
In tr od u ction
Since Tomalia1a and Newkome1b published their semi-
nal findings on well-defined “Starburst” and “arborol”
dendrimers in 1985,1 dendrimer chemistry has developed
into a mature scientific field bridging the gap between
organic and polymer chemistry.2 Until recently, the
interest in dendrimers was mainly focused on discovering
synthetic routes toward novel members of this unique
family of macromolecules. Today, however, scientists
working in this field have increasingly shifted their
attention to the modification of existing dendrimers in
order to explore the material properties of these regular
highly branched molecules. Such modifications of the
periphery of dendrons or dendrimers3 can result in
tailored materials that are potentially useful in a variety
of applications including catalysis,4 biological recogni-
tion,5 solubilization,6 and molecular encapsulation.7
Herein, we describe the surface modification of poly-
ether dendrons utilizing palladium-catalyzed cross-
coupling reactions (Scheme 1).8 Pd-catalyzed cross-
coupling reactions, such as the Suzuki,9 Negishi,10
Kumada,11 Stille,12 Hiyama,13 and Heck14 reactions, have
become important tools to facilitate asymmetric C-C
bond formation. The reaction between an organometallic
reagent (M ) B, Zn, Mg, Sn, Si), alkene, or alkyne on
one hand, and an organic electrophile (halide or triflate)
on the other hand, gives rise to the formation of the
asymmetric coupling products via a stepwise cyclic mech-
anism of Pd-complexed intermediates.14,15 Today, Pd-
catalyzed cross-coupling reactions are frequently applied
in organic16 and oligomer/polymer synthesis,17 including
the synthesis of hyperbranched polymers.18 In the field
of dendrimers, however, there are only two examples in
which Pd-catalyzed cross-coupling reactions have been
applied to prepare these well-defined molecules. Moore
et al. used a Heck reaction for the synthesis of phenyl-
acetylene dendrimers,19 whereas Miller and Neenan
applied the Suzuki reaction to prepare polyphenylene
dendrimers.20
* Corresponding author: phone, (510)-643-3077; fax, (510)-643-3079;
e-mail, frechet@cchem.berkeley.edu.
(1) (a) Tomalia, D. A.; Baker, H.; Dewald, J .; Kallos, F.; Martin, S.;
Roeck, J .; Ryder, J .; Smith, P. Polym. J . 1985, 17, 117. (b) Newkome,
G. R.; Yao, Z. Q.; Baker, G. R.; Gupta, V. K. J . Org. Chem. 1985, 50,
2003.
(2) Fre´chet, J . M. J . Science 1994, 263, 1710. Tomalia, D. A.; Durst,
H. D. Top. Curr. Chem. 1993, 165, 193. Advances in Dendritic
Macromolecules; Newkome, G. R., Ed.; J AI Press: Greenwich, 1994;
Vol. 1, 1995; Vol. 2. Newkome, G. R.; Moorefield, C. N.; Vo¨gtle, F.
Dendritic Molecules: Concepts, Synthesis, Perspectives; VCH: Wein-
heim, Germany, 1996.
(3) For some recent examples see: Leon, J . W.; Kawa, M.; Fre´chet,
J . M. J . J . Am. Chem. Soc. 1996, 118, 8847. Balagurusamy, V. S. K.;
Ungar, G.; Percec, V.; J ohansson, G. J . Am. Chem. Soc. 1997, 119,
1539. Lorenz, K.; Ho¨lter, D.; Stu¨hn, B.; Mu¨lhaupt, R.; Frey, H. Adv.
Mater. 1996, 8, 414.
(9) Martin, A. R.; Yang, Y. Acta Chem. Scand. 1993, 47, 221.
Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(10) Negishi, E.-I. Pure Appl. Chem. 1981, 53, 2333. Negishi, E.-I.
Current Trends in Organic Chemistry; Pergamon Press: Oxford, U.K.,
1983.
(11) Kalanin, V. N. Synthesis 1992, 413. Kumada, M. Pure Appl.
Chem. 1980, 52, 669.
(12) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508.
Mitchell, T. N. Synthesis 1992, 803.
(13) Hatanaka, Y.; Hiyama, T. Synlett 1991, 845. Hiyama, T.;
Hatanaka, Y. Pure Appl. Chem. 1994, 66, 1471.
(14) Heck, R. F. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 4, pp 833.
(15) Amatore, C.; J utand, A.; Suarez, A. J . Am. Chem. Soc. 1993,
115, 9531.
(4) Knapen, J . W. J .; van der Made, A. W.; de Wilde, J . C.; van
Leeuwen, A. W.; Wijkens, P.; Grove, D. M.; van Koten, G. Nature 1994,
372, 659. Lee, J .; Ford, W. T.; Moore, J . A.; Li, Y. Macromolecules 1994,
27, 4632.
(5) Newkome, G. R.; Lin, X.; Weic, C. D. Tetrahedron: Asymmetry
1991, 2, 957. Roy, R.; Zanini, D.; Meurier, S. J .; Romanowska, A. J .
Chem. Soc., Chem. Commun. 1993, 1869. Aoi, K.; Itoh, K.; Okada, M.
Macromolecules 1995, 28, 5391.
(6) Hawker, C. J .; Wooley, K. L.; Fre´chet, J . M. J . J . Chem. Soc.,
Perkin Trans. 1 1993, 1287. Newkome, G. R.; Moorefield, C. N.; Baker,
G. R.; J ohnson, A. L.; Behera, R. K. Angew. Chem., Int. Ed. Engl. 1991,
30, 1176. Mattei, S.; Seiler, P.; Diederich, F.; Gramlich, V. Helv. Chim.
Acta 1995, 78, 1904.
(7) J ansen, J . F. G. A.; de Brabander-van de Berg, E. M. M.; Meijer,
E. W. Science 1994, 266, 1226. J ansen, J . F. G. A.; Meijer, E. W.; de
Brabander-van den Berg, E. M. M. J . Am. Chem. Soc. 1995, 117, 4417.
(8) For reviews see: Negishi, E. Organometallics in Organic Syn-
thesis; J ohn Wiley and Sons: New York, 1980; Vol. 1. Collman, J . P.;
Hegedus, L. S.; Norton, J . R.; Finke, R. G. Principles and Applications
of Organotransition Metal Chemistry; University Science Books: Mill
Valley, CA, 1987. Heck, R. F. Palladium Reagents in Organic Synthesis;
Academic Press: Orlando, FL, 1985.
(16) For examples see: Stille, J . K.; Groh, B. L. J . Am. Chem. Soc.
1987, 109, 813. Smith, G. B.; Hughes, D. L.; Verhoeven, T. R. J . Org.
Chem. 1994, 59, 8151. Plunkett, M. J .; Ellman, J . A. J . Am. Chem.
Soc. 1995, 117, 3306. Larsen, M.; J ørgensen, M. J . Org. Chem. 1997,
62, 4171.
(17) For examples on oligomers see: Galda, P.; Rehahn, M. Synthesis
1996, 614. Nelson, J . C.; Young, J . K.; Moore, J . S. J . Org. Chem. 1996,
61, 8160. Groenendaal, L.; Bruining, M. J .; Hendrickx, E. H. J .;
Persoons, A.; Vekemans, J . A. J . M.; Havinga, E. E.; Meijer, E. W.
Chem. Mater. 1997, in press. Electronic Materials: The Oligomer
Approach; Wegner, G., Mu¨llen, K., Eds.; VCH: Weinheim, Germany,
1997. For examples on polymers see: Rehahn, M.; Schlu¨ter, A.-D.;
Wegner, G. Makromol. Chem. 1990, 191, 1991. McCullough, R. D.;
Lowe, R. D. J . Chem. Soc., Chem. Commun. 1992, 70. Bao, Z.; Chan,
W. K.; Yu, L. J . Am. Chem. Soc. 1995, 117, 12426. Tour, J . M. Chem.
Rev. 1996, 96, 537.
(18) Kim, Y. H.; Webster, O. W. J . Am. Chem. Soc. 1990, 112, 4592.
(19) Moore, J . S.; Xu, Z. Macromolecules 1991, 24, 5893. Xu, Z.;
Moore, J . S. Angew. Chem., Int. Ed. Engl. 1993, 32, 1354.
(20) Miller, T. M.; Neenan, T. X. Chem. Mater. 1990, 2, 346. Miller,
T. M.; Neenan, T. X.; Zayas, R.; Bair, H. E. J . Am. Chem. Soc. 1992,
114, 1018.
S0022-3263(98)00380-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/09/1998

5676 J . Org. Chem., Vol. 63, No. 16, 1998
Notes
Sch em e 2
This is the first time that Pd-catalyzed cross-coupling
reactions have been utilized to functionalize the surface
of dendrons (Scheme 1). To obtain acceptable yields of
fully functionalized dendrons of the highest generation,
the yield per coupling reaction (y/c) has to be high. For
example, to obtain a fully functionalized [G-3] dendron,
a process that requires eight cross-coupling reactions per
dendron, in an overall yield of 50%, each coupling
reaction must proceed in 92% yield. Utilizing 4-bro-
n
mophenyl terminated dendrons (Br2 -[G-n]-OH, n )
1-3)21 as the electrophiles, and performing Suzuki9
coupling reactions with phenylboronic acid, or Stille12
reactions with 2-trimethylstannylthiophene and 2-tri-
methyl-stannylpyridine, the periphery of the dendrons
has been fully functionalized with phenyl, 2-thienyl, and
2-pyridyl substituents in place of the original 4-bromo
moieties.
Resu lts a n d Discu ssion
Su zu k i Rea ction s. A Suzuki reaction between Br2-
[G-1]-OH (1)21 and 2.4 equiv of phenylboronic acid was
performed in a two-phase system consisting of toluene
and aqueous Na2CO3 (1 M), using Pd(PPh3)4 as the
catalyst. Following workup and purification, the desired
product Ph2-[G-1]-OH (6) was isolated in 81% yield
(Scheme 2). Similarly, the second and third generation
4-bromophenyl substituted dendrons, Br4-[G-2]-OH (2)
and Br8-[G-3]-OH (3),21 were fully functionalized using
excess phenylboronic acid (yields: 71% and 49% for Ph4-
[G-2]-OH (7) and Ph8-[G-3]-OH (8), respectively). Al-
though the overall yields of the Suzuki reactions decrease
with increasing dendron generation, the yield per cou-
pling (y/c; 2, 4, and 8 couplings/dendron, respectively) is
constant: 90%, 92%, and 91%, respectively (Figure 1).
Stille Rea ction s. Initially, studies were performed
to optimize the conditions for the Stille reaction between
Br2-[G-1]-OH (1) and 2-trialkylstannylthiophene. By
varying the solvent (toluene, toluene/aqueous Na2CO3 (1
M), THF), the catalyst (Pd(PPh3)4, Pd(PPh3)2Cl2) and the
stannane (2-trimethylstannyl-thiophene (4),22 2-tributyl-
stannylthiophene), the highest yield for th2-[G-1]-OH (9)
was obtained in the case of toluene/Pd(PPh3)4 using 2.3
(21) Wooley, K. L.; Hawker, C. J .; Fre´chet, J . M. J . J . Chem. Soc.,
Perkin Trans. 1 1991, 1059.
(22) For stannylation of thiophenes see: Bao, Z.; Chan, W.; Yu, L.
Chem. Mater. 1993, 5, 2.
F igu r e 1. Functionalized dendrons 6-14 as prepared by the
Suzuki or Stille reaction.

Notes
J . Org. Chem., Vol. 63, No. 16, 1998 5677
equiv of stannane 4 (78% after workup and purification).
These conditions were subsequently applied to modify the
second and third generation of 4-bromophenyl substi-
tuted dendrons, resulting in the fully 2-thienyl function-
alized species th4-[G-2]-OH (10) and th8-[G-3]-OH (11) in
86% and 46% yield, respectively. The yield per coupling
(y/c) for all three generations is 88%, 96%, and 91%,
respectively. In a similar fashion, the 4-bromophenyl
substituted dendrons were modified with 2-pyridyl units.
Using excess 2-trimethylstannylpyridine (5)23 as the
stannane, and again performing the reactions in toluene/
Pd(PPh3)4, the dendrons pyr2-[G-1]-OH (12), pyr4-[G-2]-
OH (13), and pyr8-[G-3]-OH (14) were obtained in yields
of 53%, 43%, and 31%, respectively (yield per coupling is
73%, 81%, and 87%, respectively; Figure 1).
Although the yield per coupling (y/c) remains es-
sentially constant (∼91%) for the phenyl and 2-thienyl
functionalization reactions, this value is somewhat lower
in case of the 2-pyridyl modifications. This finding is
related to difficulties encountered in the purification of
the pyridyl-modified dendrons. During the functional-
ization reaction, homo-coupling of the stannane occurs,
which leads to the formation of 2,2′-bipyridine. Since this
compound has almost the same Rf value as that of the
desired Stille product, purification is difficult and the
yields, and thus the y/c, are significantly lower than is
the case for the phenyl or the 2-thienyl derivatives.
1
Examination of pyr2-[G-1]-OH (12) by H NMR spec-
troscopy revealed an interesting feature of this com-
pound. The resonance attributed to the OH proton was
observed downfield at 2.69 ppm instead of the chemical
shift of 1.7-1.9 ppm normally expected for such a
structure. Similar observations were made in the cases
of pyr4-[G-2]-OH (13) and pyr8-[G-3]-OH (14). These
results suggest the occurrence of intermolecular hydrogen
bonding between the nitrogen of the pyridyl unit at the
periphery of the dendron and the OH group at the focal
point of the dendron. In the case of dendron 12, we were
able to obtain crystals suitable for X-ray crystallography
by recrystallization from CH2Cl2/cyclohexane.24 The X-
ray crystal structure shown in Figure 2 confirms clearly
the existence of strong H-bonds between the nitrogen of
the pyridyl unit at the periphery of the dendron and the
OH group at the focal point of the dendron, resulting in
a unit cell consisting of dimers formed through two
intermolecular H-bonds. Unfortunately, neither dendron
13 nor dendron 14 was crystalline material.
F igu r e 2. Dimers, as formed by two intermolecular H-bonds,
within the crystal structure of pyr2-[G-1]-OH (12).
modify the periphery of polyether dendrons with a variety
of other substituents using Suzuki, Stille, as well as Heck
reactions. In the latter case, further studies are required
since the bis-stilbene product obtained by reaction be-
tween Br2-[G-1]-OH (1) and 4-acetoxystyrene (Pd(OAc)2,
(o-tol)3P, Bu3N, DMF; 82% yield after purification) is only
slightly soluble in common organic solvents.
Exp er im en ta l Section
All chemicals were reagent grade and used without further
purification. The 4-bromine-substituted dendrons 1, 2, and 3
were prepared according to a procedure reported by Fre´chet et
al.21 2-Trimethylstannylthiophene (4)22 and 2-trimethylstan-
nylpyridine (5)23 were prepared from 2-bromothiophene and
2-bromopyridine, respectively, applying a standard Br-Li ex-
change (n-BuLi)/stannylation ((CH3)3SnCl) sequence. Thin-layer
chromatography was performed on Whatman TLC plates (Al Sil
G/UV254 (250 µm)). Chromatographic separations were per-
formed on silica gel 60 (SiO2, 0.040-0.063 mm, 230-400 mesh).
Melting points are uncorrected. 1H and 13C NMR data were
recorded on a 400 MHz spectrometer using TMS as internal
standard. Mass spectrometry data were obtained using EI-MS,
FAB-MS, or MALDI-TOF MS (operated in delayed extraction
mode using trans-3-indoleacrylic acid or R-cyano-4-hydroxycin-
namic acid as the matrix). MALDI-TOF data are reported using
relative masses since the (relatively) broad peaks obtained reflect
all isotopic compositions and the mass given represents the value
measured at the top of the peak. Elemental analyses were
conducted by MHW Laboratories, Phoenix, AZ.
In conclusion, we have shown that both Suzuki and
the Stille coupling reactions can be applied to function-
alize the periphery of polyether dendrons. Starting from
n
4-bromo-substituted dendrons Br2 -[G-n]-OH (n ) 1-3)
and applying Pd-catalyzed cross-coupling reactions, the
surfaces of these species have been fully functionalized
with phenyl, 2-thienyl, and 2-pyridyl substituents in
moderate to good yields using phenylboronic acid, 2-tri-
methylstannylthiophene, and 2-trimethylstannylpyri-
dine, respectively. Although the overall yields of the
coupling reactions decrease with increasing generation,
the yield per coupling (y/c) is relatively constant (91%
for phenyl and 2-thienyl substitution, and 80% for
2-pyridyl substitution). Currently, we are attempting to
P h 2-[G-1]-OH (6) (Gen er a l p r oced u r e for a Su zu k i r ea c-
tion ). A 100 mL flask with gas-inlet was charged with Br2-[G-
1]-OH (1, 738 mg, 1.542 mmol), toluene (6 mL), aqueous Na2CO3
(6 mL, 1 M), and phenylboronic acid (457 mg, 3.748 mmol). The
mixture was stirred under argon atmosphere for 10 min, after
which it was deaerated 7 times, each time saturating with argon.
Then Pd(PPh3)4 (2 mol %) was added and the yellow mixture
(23) For stannylation of pyridines see: Ca´rdenas, D. J .; Sauvage,
J .-P. Synlett 1996, 916.
(24) Colorless platelike crystals: 0.08 × 0.24 × 0.35 mm; O1‚‚‚N1,
2.827 Å; O1-H1, 0.95 Å; N1‚‚‚H1, 1.93 Å; O1-H1‚‚‚N1, 185°. For more
details, refer to the corresponding author.

5678 J . Org. Chem., Vol. 63, No. 16, 1998
Notes
was refluxed for 20 h. The brown organic phase was separated,
and the aqueous Na2CO3 phase was extracted with CH2Cl2. The
combined organic fractions were washed with H2O, dried
(MgSO4), and filtered, and the solvent was evaporated. Recrys-
tallization from CH2Cl2/cyclohexane finally resulted in 6 as a
white solid (589 mg, 1.25 mmol, 81%): mp 136.5-138.0 °C. 1H
NMR (CDCl3): δ 7.58 (2 × d, J ) 8.2 Hz, 8H), 7.50-7.41 (m,
8H), 7.35 (t, J ) 7.3 Hz, 2H), 6.66 (d, J ) 2.1 Hz, 2H), 6.59 (t, J
) 2.1 Hz, 1H), 5.08 (s, 4H), 4.64 (d, J ) 5.7 Hz, 2H), 1.73 (t, J
) 5.9 Hz, 1H) ppm 13C NMR (CDCl3): δ 160.2, 143.5, 141.0,
140.7, 135.8, 128.8, 128.0, 127.3, 127.1, 105.8, 101.3, 69.8, 65.3
ppm FT-IR (KBr): ν 3294, 3054, 3031, 2908, 2865, 1592, 1163,
1059, 1006, 828, 757, 695 cm-1. UV-vis (CHCl3): λmax 256 nm;
EI-MS m/z 472 (M+), 333, 305, 167; FAB-MS m/z 473 (M + H+),
455, 167. Anal calcd for C33H28O3: C, 83.87; H, 5.97. Found:
C, 83.60; H, 5.97.
134.1, 128.0, 126.1, 124.9, 123.2, 105.8, 101.3, 69.7, 65.3 ppm.
FT-IR (KBr): ν 3385, 3279, 3100, 2904, 2862, 1593, 1445, 1376,
1319, 1163, 812, 692 cm-1; UV-vis 288 nm. EI-MS m/z 484
(M+), 345, 311, 173. FAB-MS: m/z 485 (M + H+), 467, 441, 173.
Anal calcd for C29H24O3S2: C, 71.87; H, 4.99; S, 13.23. Found:
C, 72.04; H, 5.20; S, 13.00.
th 4-[G-2]-OH (10). A Stille reaction between Br4-[G-2]-OH
(2, 368 mg, 0.347 mmol) and 2-trimethylstannylthiophene (4,
478 mg, 1.936 mmol) in toluene (6 mL) with Pd(PPh3)4 as the
catalyst was performed as described for 9. After 2 days the
reaction was complete and the mixture was allowed to cool to
room temperature. Extraction (CH2Cl2/H2O) gave a solid that
was purified by column chromatography (20 g of SiO2, CHCl3
as eluent, Rf . 0.16). Final recrystallization (CH2Cl2/cyclohex-
ane) resulted in 10 as a fine, white powder (320 mg, 0.298 mmol,
86%). 1H NMR (CDCl3): δ 7.60 (d, J ) 8.2 Hz, 8H), 7.40 (d, J
) 8.2 Hz, 8H), 7.30 (dd, J ) 3.6 and 1.1 Hz, 4H), 7.27 (dd, J )
5.1 and 1.1 Hz, 4H), 7.07 (dd, J ) 5.1 and 3.6 Hz, 4H), 6.69 (d,
J ) 2.1 Hz, 4H), 6.60 (d, J ) 2.0 Hz, 2H), 6.58 (t, J ) 2.1 Hz,
2H), 6.54 (t, J ) 2.1 Hz, 1H), 5.01 (s, 8H), 4.96 (s, 4H), 4.57 (d,
P h 4-[G-2]-OH (7). A Suzuki reaction between Br4-[G-2]-OH
(2, 258 mg, 0.243 mmol) and phenylboronic acid (151 mg, 1.238
mmol) in toluene (3.5 mL) and aqueous Na2CO3(3.5 mL, 1 M)
with Pd0(PPh3)4 as the catalyst was performed as described for
6. After 20 h the reaction was complete and the mixture was
allowed to cool to room temperature. Extraction (CH2Cl2/H2O)
gave a solid that was purified by column chromatography (25 g
of SiO2, CH2Cl2, Rf . 0.39). Subsequent recrystallization (CH2-
Cl2/cyclohexane) resulted in 7 as a fine, white powder (182 mg,
0.173 mmol, 71%). 1H NMR (CDCl3): δ 7.61 (m, 16H), 7.47 (m,
16H), 7.36 (t, J ) 7.4 Hz, 4H), 6.72 (d, J ) 2.2 Hz, 4H), 6.62 (m,
4H), 6.56 (t, J ) 2.2 Hz, 1H), 5.08 (s, 8H), 5.00 (s, 4H), 4.61 (d,
J
) 6.0 Hz, 2H), 1.86 (t, J ) 6.1 Hz, 1H) ppm. 13C NMR
(CDCl3): δ 160.0, 159.9, 143.9, 143.5, 139.3, 135.9, 134.0, 128.04,
128.00, 126.0, 124.9, 123.2, 106.3, 105.6, 101.6, 101.2, 69.8, 69.7,
65.1 ppm. FT-IR (KBr): ν 3569, 3456, 3104, 3069, 2923, 2869,
1595, 1448, 1371, 1159, 1051, 811, 699 cm-1. UV-vis (CHCl3):
λmax 288 nm. MALDI-TOF MS: m/z calcd for C65H52O7S4:
1073.4 (M+), 1096.4 (M + Na+), 1112.5 (M + K+). Found: 1073.6
(M+), 1096.9 (M + Na+), 1113.0 (M + K+). Anal calcd for
J
) 6.0 Hz, 2H), 1.71 (t, J ) 6.1 Hz, 1H) ppm. 13C NMR
C65H52O7S4: C, 72.73; H, 4.88; S, 11.95. Found: C, 72.58; H,
4.92; S, 12.13.
(CDCl3): δ 160.15, 160.03, 143.4, 140.9, 140.7, 139.4, 135.7,
128.8, 128.0, 127.3, 127.1, 106.4, 105.7, 101.6, 101.3, 69.90, 69.85,
65.2 ppm. FT-IR (KBr): ν 3560, 3056, 3029, 2912, 2868, 1595,
1163, 1050, 827, 760, 697 cm-1. UV-vis (CHCl3): λmax 254 nm.
MALDI-TOF MS m/z calcd for C73H60O7: 1049.3 (M+), 1072.3
(M + Na+), 1088.4 (M + K+). Found: 1049.0 (M+), 1071.6 (M +
Na+), 1087.8 (M + K+). Anal calcd for C73H60O7: C, 83.56; H,
5.76. Found: C, 83.38; H, 5.84.
th 8-[G-3]-OH (11). A Stille reaction between Br8-[G-3]-OH
(3, 278 mg, 0.125 mmol) and 2-trimethylstannylthiophene (4,
525 mg, 2.13 mmol) in toluene (3 mL) with Pd0(PPh3)4 as the
catalyst was performed as described for 9. After 48 h the
reaction was complete and the mixture was allowed to cool to
room temperature. Extraction (CH2Cl2/H2O) gave a solid that
was purified by column chromatography (35 g of SiO2, CHCl3
as eluent, Rf . 0.12). The latter resulted in pure 11 as a slightly
yellow foam (130 mg, 0.0578 mmol, 46%). 1H NMR (CDCl3): δ
7.52 (d, J ) 8.3 Hz, 16H), 7.31 (d, J ) 8.3 Hz, 16H), 7.22 (dd, J
) 3.6 and 1.1 Hz, 8H), 7.20 (dd, J ) 5.1 and 1.1 Hz, 8H), 7.00
(dd, J ) 5.1 and 3.6 Hz, 8H), 6.64 (d, J ) 2.2 Hz, 8H), 6.62 (d,
J ) 2.2 Hz, 4H), 6.56 (d, J ) 2.1 Hz, 2H), 6.54 (t, J ) 2.2 Hz,
4H), 6.51 (t, J ) 2.1 Hz, 2H), 6.47 (t, J ) 2.1 Hz, 1H), 4.90 (s,
16H), 4.86 (s, 8H), 4.84 (s, 4H), 4.48 (broad s, 2H), 1.86 (broad
s, 1H) ppm. 13C NMR (CDCl3): δ 159.98, 159.94, 159.91, 143.9,
143.6, 139.34, 139.27, 135.9, 134.0, 128.02, 125.9, 127.98, 124.8,
123.2, 106.3, 105.6, 101.58, 101.49, 101.14, 69.80, 69.76, 69.62,
65.03 ppm. FT-IR (KBr): ν 3570, 3100, 3070, 2923, 2871, 1595,
1449, 1372, 1158, 1048, 811, 699 cm-1; UV-vis (CHCl3): λmax
288 nm. MALDI-TOF MS: m/z calcd for C137H108O15S8: 2273.9
(M + Na+), 2290.0 (M + K+). Found: 2273.3 (M + Na+), 2289.9
(M + K+). Anal calcd for C137H108O15S8: C, 73.10; H, 4.84; S,
11.40. Found: C, 72.97; H, 5.00; S, 11.60.
P h 8-[G-3]-OH (8). A Suzuki reaction between Br8-[G-3]-OH
(3, 267 mg, 0.120 mmol) and phenylboronic acid (157 mg, 1.29
mmol) in toluene (5 mL) and aqueous Na2CO3 (5 mL, 1 M) with
Pd0(PPh3)4 as the catalyst was performed as described for 6.
After 48 h the reaction was complete and the mixture was
allowed to cool to room temperature. Extraction (CHCl3/H2O)
gave a solid that was purified by column chromatography (25 g
of SiO2, CHCl3 as eluent, Rf . 0.20). The latter resulted in pure
8 as a white foam (129 mg, 0.059 mmol, 49%). 1H NMR
(CDCl3): δ 7.58 (m, 32H), 7.44 (m, 32H), 7.36 (t, J ) 7.3 Hz,
8H), 6.71 (d, J ) 2.1 Hz, 8H), 6.68 (d, J ) 2.0 Hz, 4H), 6.62 (t,
J ) 2.1 Hz, 4H), 6.59 (d, J ) 2.0 Hz, 2H), 6.57 (t, J ) 2.0 Hz,
2H), 6.53 (t, J ) 2.0 Hz, 1H), 5.01 (s, 16H), 4.92 (s, 8H), 4.91 (s,
4H), 4.53 (d, J ) 6.0 Hz, 2H), 1.70 (t, J ) 6.1 Hz, 1H) ppm. 13C
NMR (CDCl3): δ 160.14, 160.03, 143.5, 140.9, 140.7, 139.37,
139.30, 135.7, 128.8, 128.0, 127.3, 127.1, 106.4, 105.8, 101.64,
101.60, 101.25, 69.93, 69.83, 65.2 ppm. FT-IR (KBr): ν 3570,
3054, 3029, 2926, 2871, 1595, 1157, 1052, 829, 760, 697 cm-1
.
p yr 2-[G-1]-OH (12). A Stille reaction between Br2-[G-1]-OH
(1, 336 mg, 0.703 mmol) and 2-trimethylstannylpyridine (5, 431
mg, 1.782 mmol) in toluene (6 mL) with Pd0(PPh3)4 as the
catalyst was performed as described for 9. After 48 h the
reaction was complete and the mixture was allowed to cool to
room temperature. Extraction (CH2Cl2/H2O) gave a solid that
was purified by column chromatography (25 g of SiO2, 3%
methanol in CH2Cl2, Rf . 0.36). Subsequent recrystallization
from cyclohexane/CH2Cl2 gave pure 12 as colorless platelike
crystals (178 mg, 0.375 mmol, 53%): mp 147.5-148.5 °C. 1H
NMR (CDCl3): δ 8.67 (m, 2H), 7.97 (d, J ) 8.4 Hz, 4H), 7.72
(m, 4H), 7.49 (d, J ) 8.4 Hz, 4H), 7.22 (tt, J ) 5.9 and 1.7 Hz,
2H), 6.61 (d, J ) 2.3 Hz, 2H), 6.55 (t, J ) 2.3 Hz, 1H), 5.06 (s,
4H), 4.60 (s, 2H), 2.69 (broad s, 1H) ppm. 13C NMR (CDCl3): δ
160.0, 157.0, 149.6, 143.7, 138.9, 137.7, 136.8, 127.7, 127.1, 122.1,
120.5, 105.8, 101.3, 69.7, 65.0 ppm. FT-IR (KBr): ν 3248, 3036,
2924, 2872, 1589, 1470-1295, 1155, 1045, 845, 772 cm-1. UV-
vis (CHCl3): λmax 252, 280 nm; EI-MS m/z 474 (M+), 168. Anal
calcd for C31H26N2O3: C, 78.46; H, 5.52; N, 5.90. Found: C,
78.37; H, 5.74; N, 5.71.
UV-vis (CHCl3): λmax 254 nm. MALDI-TOF MS m/z calcd for
C153H124O15: 2225.7 (M + Na+), 2241.8 (M + K+). Found: 2226.1
(M + Na+), 2242.3 (M + K+). Anal calcd for C153H124O15: C,
83.43; H, 5.67. Found: C, 83.13; H, 5.47.
th 2-[G-1]-OH (9) (Gen er a l p r oced u r e for a Stille r ea c-
tion ). A 100 mL flask with gas-inlet was charged with Br2-[G-
1]-OH (1, 334 mg, 0.698 mmol), 2-trimethylstannylthiophene (4,
392 mg, 1.587 mmol), and toluene (6 mL). The mixture was
deaerated 7 times, each times saturating with argon. Then Pd-
(PPh3)4 (2 mol %) was added and the yellow mixture was
refluxed, constantly blanketed by argon. After 2 days the
reaction was complete and the mixture was allowed to cool to
room temperature. Extraction (CH2Cl2/H2O) gave a dark oil that
was subsequently purified by column chromatography (30 g of
SiO2, eluent CH2Cl2, Rf . 0.31). Recrystallization from CH2-
Cl2/cyclohexane finally resulted in pure 9 as a white solid (264
mg, 0.545 mmol, 78%): mp 147.5-149 °C. 1H NMR (CDCl3): δ
7.60 (d, J ) 8.3 Hz, 4H), 7.40 (d, J ) 8.4 Hz, 4H), 7.30 (dd, J )
3.6 and 1.1 Hz, 2H), 7.26 (dd, J ) 5.1 and 1.1 Hz, 2H), 7.07 (dd,
J ) 5.0 and 3.6 Hz, 2H), 6.62 (d, J ) 2.2 Hz, 2H), 6.54 (t, J )
2.2 Hz, 1H), 5.02 (s, 4H), 4.61 (d, J ) 4.8 Hz, 2H), 1.78 (t, J )
4.5 Hz, 1H). 13C NMR (CDCl3): δ 160.0, 143.9, 143.5, 136.0,
p yr 4-[G-2]-OH (13). A Stille reaction between Br4-[G-2]-OH
(2, 323 mg, 0.305 mmol) and 2-trimethylstannylpyridine (5, 371
mg, 1.534 mmol) in toluene (5 mL) with Pd0(PPh3)4 as the

Notes
J . Org. Chem., Vol. 63, No. 16, 1998 5679
catalyst was performed as described for 9. After 24 h the
reaction was complete and the mixture was allowed to cool to
room temperature. Extraction (CH2Cl2/H2O) gave a brown oil
that was purified by column chromatography (35 g SiO2, 3%
methanol in CH2Cl2 as eluent, Rf . 0.35). Final recrystallization
(CH2Cl2/cyclohexane) resulted in pure 13 as a fine, white powder
(137 mg, 0.130 mmol, 43%). 1H NMR (CDCl3): δ 8.68 (m, 4H),
7.97 (d, J ) 8.3 Hz, 8H), 7.71 (m, 8H), 7.47 (d, J ) 8.3 Hz, 8H),
7.23 (m, 4H), 6.64 (d, J ) 2.2 Hz, 4H), 6.57 (t, J ) 2.2 Hz, 2H),
6.48 (d, J ) 2.1 Hz, 2H), 6.45 (t, J ) 2.2 Hz, 1H), 5.09 (s, 8H),
4.95 (s, 4H), 4.56 (s, 2H), 3.45 (broad s, 1H) ppm. 13C NMR
(CDCl3): δ 159.9, 159.7, 157.0, 149.6, 144.0, 139.5, 138.9, 137.6,
136.8, 127.7, 127.1, 122.2, 120.6, 106.1, 105.5, 101.7, 101.0, 69.69,
69.61, 64.7 ppm. FT-IR (KBr): ν 3254, 3053, 2922, 2852, 1589,
material that was purified by column chromatography (60 g of
SiO2, 3-5% methanol in CH2Cl2 as eluent, Rf (3%) . 0.28). This
finally resulted in pure 14 as a white foam (104 mg, 0.047 mmol,
31%). 1H NMR (CDCl3): δ 8.67 (m, 8H), 7.97 (d, J ) 8.3 Hz,
16H), 7.68 (m, 8H), 7.48 (d, J ) 8.3 Hz, 16H), 7.19 (m, 8H), 6.67
(d, J ) 2,2 Hz, 8H), 6.64 (d, J ) 2.1 Hz, 8H), 6.57 (m, 6H), 6.53
(t, J ) 2.2 Hz, 2H), 6.49 (t, J ) 2.2 Hz, 1H), 5.05 (s, 16H), 4.94
(s, 8H), 4.91 (s, 4H), 4.54 (s, 2H), 3.07 (broad s, 1H) ppm. 13C
NMR (CDCl3): δ 160.01, 159.95, 159.90, 156.9, 149.6, 143.8,
139.36, 139.30, 138.9, 137.6, 136.7, 127.7, 127.0, 122.1, 120.5,
106.4, 105.7, 101.66, 101.55, 101.08, 69.86, 69.80, 69.70, 64.9
ppm. FT-IR (KBr): ν 3280, 3051, 2923, 2870, 1593, 1467, 1153,
1059, 832, 777 cm-1. UV-vis (CHCl3): λmax 250, 280 nm.
MALDI-TOF MS m/z calcd for C145H116N8O15: 2211.6 (M + H+),
2233.6 (M + Na+). Found: 2212.2 (M + H+), 2234.3 (M + Na+).
1467, 1157, 1055, 833, 777 cm-1
. UV-vis (CHCl3): λmax 252,
282 nm. MALDI-TOF MS: m/z calcd for C69H56N4O7: 1054.4 (M
+ H+), 1076.4 (M + Na+); found: 1054.7 (M + H+), 1076.9 (M +
Na+). HR-MS m/z calcd for C69H56N4O7: 1053.4227. Found:
1053.4232.
p yr 8-[G-3]-OH (14). A Stille reaction between Br8-[G-3]-OH
(3, 337 mg, 0.1516 mmol) and 2-trimethylstannylpyridine (5, 427
mg, 1.577 mmol) in toluene (6 mL) with Pd0(PPh3)4 as the
catalyst was performed as described for 9. After 40 h the
reaction was complete and the mixture was allowed to cool to
room temperature. Extraction (CHCl3/H2O) gave a dark spongy
Anal calcd for
C145H116N8O15: C, 78.79; H, 5.29; N, 5.07.
Found: C, 78.76; H, 5.43; N, 4.84.
Ack n ow led gm en t. This research was supported by
the National Science Foundation (DMR 9796106); par-
tial support of BG by The Netherlands Organization for
Scientific Research (NWO) is also acknowledged with
thanks.
J O980380V