Synthesis of a chiral micelle-like dendrimer with phenylene dendrons and a 1,1′-binaphthyl core

Article abstract of DOI:10.1016/S0040-4039(01)01569-6

A novel chiral micelle-like dendrimer has been synthesized. This dendrimer contains a chiral binaphthyl core, meta-phenylene dendrons, and hydrophilic polyhydroxyl periphery groups. It is soluble in highly polar solvents such H₂O/THF, MeOH/THF, EtOH/THF and DMSO, but insoluble in EtOAc, CH₂Cl₂ and CHCl₃. The study by UV-vis absorption spectroscopy reveals that the dendrimer may have a tighter conformation in a less polar solvent than in a more polar solvent. This dendrimer shows strong fluorescence in solution.

Full text of DOI:10.1016/S0040-4039(01)01569-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7337–7340
Synthesis of a chiral micelle-like dendrimer with phenylene
dendrons and a 1,1%-binaphthyl core
Liu-Zhu Gong† and Lin Pu*
Department of Chemistry, University of Virginia, Charlottesville, VA 22904-4319, USA
Received 3 August 2001; revised 20 August 2001; accepted 21 August 2001
Abstract—A novel chiral micelle-like dendrimer has been synthesized. This dendrimer contains a chiral binaphthyl core,
meta-phenylene dendrons, and hydrophilic polyhydroxyl periphery groups. It is soluble in highly polar solvents such H2O/THF,
MeOH/THF, EtOH/THF and DMSO, but insoluble in EtOAc, CH2Cl2 and CHCl3. The study by UV–vis absorption
spectroscopy reveals that the dendrimer may have a tighter conformation in a less polar solvent than in a more polar solvent. This
dendrimer shows strong fluorescence in solution. © 2001 Published by Elsevier Science Ltd.
In the past two decades, a tremendous amount of study
has been carried out on dendritic materials.1–3 Unlike
conventional polymers, dendrimers have well defined
structures with specific shape, size and surface func-
tional groups. By introducing hydrophilic peripheral
groups to the hydrophobic branches and cores of den-
drimers, materials of micelle-like structures have been
designed and synthesized.4,5 Application of these uni-
Scheme 1. Synthesis of the highly functionalized second generation dendron 10.
Keywords: chiral dendrimer; unimolecular micelle.
* Corresponding author. E-mail: lp6n@virginia.edu
† Current address: Union Laboratory of Asymmetric Synthesis, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences.
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)01569-6

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L.-Z. Gong, L. Pu / Tetrahedron Letters 42 (2001) 7337–7340
molecular micelles in areas such as drug delivery and
medical image is under active investigation. This type
of dendritic hosts not only can solubilize organic drug
molecules in aqueous media by inclusion, but also
provides a much more stable structure than the normal
micelles that are susceptible to disintegration with the
change of concentration, pH, temperature and other
factors.6 Because of the covalent bonds in dendrimers,
their micelle-like structures will remain intact before
bond cleavage. Chiral dendritic micelles have also been
synthesized.7,8 These materials are potentially useful for
molecular recognition and chiral sensing in highly polar
media. Recently, we have studied the use of optically
active light harvesting dendrimers to build highly sensi-
tive fluorescent sensors for the enantioselective recogni-
tion of chiral organic compounds.9 In order to carry
out such recognition in solvents of high polarity, we
have synthesized a novel micelle-like chiral dendrimer
that contains polyhydroxyl periphery groups, cross-
conjugated phenylene dendrons, and a chiral binaph-
thyl core.10 Herein, the synthesis and characterization
of this material is reported.
pound 1 was first protected with TBS group. Then, the
two ester groups were reduced with LiAlH4 and the
resulting two hydroxyl groups were protected with
MOM groups to give 2. The TBS group of 2 was
removed with Bu4NF and the resulting phenol hydroxyl
group was converted to a triflate to form 3. This
compound was coupled with diborate 4 in the presence
of Pd(dppf)Cl2 to give the first generation dendron 5.11
The TMS group of 5 was converted to an iodide by
reacting with NaI and NCS to form 6.12a The Suzuki
coupling of 6 with 4 gave the second generation den-
dron 7.11 Conversion of the TMS group of 7 to an
iodide produced compound 8 which was then reacted
with 9 to give the desired second generation dendritic
borate 10.11a,12b,13
Following our previously established procedure, opti-
cally pure (R)-1,1%-bi-2-naphthol [(R)-BINOL] was first
alkylated to (R)-11 which was then converted to the
4,4%,6,6%-tetrabrominated compound (R)-12 (Scheme
2).9 The Suzuki coupling of (R)-12 with dendron 10 was
catalyzed by Pd(PPh3)4 over 4 d to give dendrimer
(R)-13 in 67% yield.14,15 The 1H NMR spectrum of
(R)-13 was consistent with its structure. A singlet at l
8.44 ppm was assigned to H-5 of the binaphthyl unit
Highly functionalized meta-phenylene-based dendrons
were prepared for the synthesis of the desired den-
drimer (Scheme 1). The commercially available com-
Scheme 2. Synthesis of the micelle-like chiral dendrimer (R)-14.

L.-Z. Gong, L. Pu / Tetrahedron Letters 42 (2001) 7337–7340
7339
Figure 1. UV spectra of (R)-14 in THF and H2O/THF.
indicating a C2-symmetric structure. Two singlet peaks
at l 3.31 and 3.33 containing 96 protons corresponded
potentially useful for the optical recognition of chiral
organic molecules in highly polar media.
to the (OCH2OCH3 32
singlet peaks at l 4.55, 4.51, 4.61 and 4.64 ppm were
assigned to the protons of the (Ar-CH2OCH2OCH3)32
6
)
groups on the periphery. Four
Acknowledgements
6
6
groups. After this dendrimer was treated with 6N HCl
in CHCl3 and EtOH under reflux to remove the MOM
groups, the desired second generation micelle-like chiral
The support of this work from the National Institute of
Health (1R01GM58454) is gratefully acknowledged.
We also thank the partial support from the donors of
the Petroleum Research Fund—administered by the
American Chemical Society.
1
dendrimer (R)-14 was obtained.14 The H NMR spec-
trum of (R)-14 was compared with that of (R)-13. It
showed that the -OCH6 2OCH6 3 signals in (R)-13 disap-
peared and a new singlet appeared at l 4.51 with 64
protons corresponding to the (ArCH2OH)32 groups of
6
(R)-14. This indicates that all the MOM groups of
(R)-13 were completely hydrolyzed. The 13C NMR
spectrum of (R)-14 also supported the structure. In the
13C NMR spectrum, a strong peak at l 62.97 was
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The UV spectrum of (R)-14 in THF displayed absorp-
tion umax at 260 (sh), 288, 310 (sh), and 361 (sh) nm
(Fig. 1). When the solvent was changed to H2O/THF
(3:1), the absorption signals became much broader. The
absorption band width at m/2 increased from 52 nm in
THF to 89 nm in H2O/THF with very little changes in
the peak positions. This large increase in absorption
band width as the polarity of the solvent increases
indicates that the dendrimer might have a much tighter
conformation in THF than in H2O/THF probably due
to different degree of inter- versus intramolecular
hydrogen bonds.16 The dendrimer was strongly fluores-
cent in both THF and H2O/THF with an emission
maximum at 407 nm. This micelle-like dendrimer is
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give 10. This compound contained a small amount of
pinacol that was difficult to remove. It was directly used
Biomembranes; Wiley-Liss: New York, 1995.
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1
for the next step. H NMR (CDCl3, 300 MHz) l 8.12 (d,
J=1.8 Hz, 2H), 8.03 (s, 1H), 7.84 (d, J=1.8 Hz, 4H),
7.79 (s, 2H), 7.61 (d, J=1.2 Hz, 8H), 7.39 (s, 4H), 4.74 (s,
16H), 4.69 (s, 16H), 3.43 (s, 24H), 1.39 (s, 12H).
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Bo¨hme, M.; Grimme, S.; Nieger, M.; Paulus, W.; Vo¨gtle,
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10. For other chiral binaphthyl-based dendrimers, see: (a)
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14. Preparation and characterization of dendrimer (R)-14: (a)
Under nitrogen, to a flask charged with (R)-12 (76 mg,
0.10 mmol), 10 (822 mg, 0.64 mmol) and Pd(PPh3)4 (22
mg, 0.02 mmol) was added degassed THF (5 mL) and
K2CO3 (2 M, 2 mL, 4.00 mmol). The mixture was heated
at reflux for 48 h. After cooled down to room tempera-
ture, the reaction solution was poured into a mixture of
EtOAc and water. The aqueous layer was extracted with
EtOAc. The combined organic layer was washed with
brine and dried over anhydrous Na2SO4. After removal
of the solvent, the residue was purified by column chro-
matography on silica gel eluted with EtOAc and EtOH
(50:1) to give (R)-13 (330 mg, 0.067 mmol) as a yellow
solid in 67% yield. 1H NMR (CDCl3, 300 MHz) l 8.44 (s,
2H), 8.01–7.63 (m, 42H), 7.55 (s, 16H), 7.49 (s, 16H), 7.32
(s, 8H), 7.29 (s, 8H), 4.65, 4.62, 4.58, 4.55 (4 singlet,
128H), 4.08 (s, 4H), 1.50 (br), 1.01 (br), 0.57 (br). 13C
NMR (CDCl3, 75 MHz) l 154.38, 142.34, 142.07, 141.67,
141.15, 138.77, 136.64, 134.27, 128.48, 127.66, 126.96,
126.33, 126.03, 125.49, 124.43, 117.78, 95.76, 69.74, 68.95,
55.30, 31.22, 29.31, 25.31, 22.45, 13.82. (b) To a solution
of (R)-13 (300 mg, 0.06 mmol) in EtOH (ca. 30 mL) and
CHCl3 (20 mL) was added 6N HCl (20 mL). After heated
at reflux for 24 h, the solvent was evaporated, and the
resulting mixture was dissolved in a mixture of THF and
EtOH and precipitated with the addition of hexane to
give (R)-14 (170 mg, 0.05 mmol) as a white solid in 80%
1
yield. H NMR (DMSO, 300 MHz) l 8.40 (br), 8.02 (br),
8.04 (br), 7.93–7.70 (m), 7.59 (s, 16H), 7.53 (s, 16H), 7.30
(s, 8H), 7.27 (s, 8H), 5.19 (m, 32H), 4.51 (br, 64H), 4.20
(br), 1.46 (br), 0.97 (br), 0.49 (br). 13C NMR (DMSO, 75
MHz) l 154.09, 143.00, 142.20, 141.86, 141.52, 141.23,
139.48, 133.70, 128.22, 126.87, 124.83, 124.42, 124.08,
123.57, 119.07, 117.70, 68.86, 62.97, 30.75, 28.92, 24.94,
21.99, 13.56. MS (MALDI) m/z 3566 (M+Na+, 100).
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see: (a) Miller, T. M.; Neenan, T. X.; Zayas, R.; Bair, H.
E. J. Am. Chem. Soc. 1992, 114, 1018–1025; (b) Wiesler,
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13. Preparation and characterization of dendron 10: In dry-
box, a flask was charged with KOAc (294 mg, 3.0 mmol),
tetraalkoxydiboron
9
(254 mg, 1.00 mmol) and
Pd(dppf)Cl2·CH2Cl2 (25 mg, 0.03 mmol). The mixture
was then combined with a degassed solution of 8 (1.1 g,
0.88 mmol) in anhydrous DMSO (5 mL) under nitrogen.
After stirred at 80°C for 8 h, the reaction mixture was
cooled to room temperature and was poured into a
mixture of EtOAc and water. The aqueous layer was
extracted with EtOAc. The combined organic layer was