Dendrimer interior functional group conversion and dendrimer metamorphosis - New approaches to the synthesis of oligo(dibenzyl sulfone) and oligo(phenylenevinylene) dendrimers

Article abstract of DOI:10.1021/ja046557m

A series of [G1] to [G3]-oligo(dibenzylsulfide) dendrimers containing up to 21 interior dibenzylsulfide moieties was prepared as starting materials toward the syntheses of two new series of oligo(dibenzyl sulfone) and oligo(phenylenevinylene) dendrimers using two different dendrimer-to-dendrimer conversion strategies. The first strategy entailed the interior functionalization of the [G1] to [G3]-oligo(dibenzylsulfide)s to the corresponding [G1] to [G3]-oligo(dibenzyl sulfone)s via hydrogen peroxide oxidation. Successful conversions of up to 21 interior dibenzylsulfide moieties to the corresponding dibenzyl sulfone groups were demonstrated. The second involved the skeletal rearrangements, also named as dendrimer metamorphosis, of the [G1] and [G2]-oligo(dibenzyl sulfone) dendritic backbones to the corresponding [G1] and [G2]-oligo-(phenylenevinylene)s dendrimers via the Ramberg-Baecklund (RB) reaction. Up to nine RB rearrangements on a dendrimer skeleton were realized and the conversion efficiency of each single RB rearrangement reaction was found to be 96%.

Full text of DOI:10.1021/ja046557m

Published on Web 09/18/2004
Dendrimer Interior Functional Group Conversion and
Dendrimer Metamorphosis-New Approaches to the Synthesis
of Oligo(dibenzyl sulfone) and Oligo(phenylenevinylene)
Dendrimers
Hak-Fun Chow,* Man-Kit Ng, Chi-Wing Leung, and Guo-Xin Wang
Contribution from the Department of Chemistry, The Chinese UniVersity of Hong Kong,
Shatin, NT, Hong Kong SAR
Received June 11, 2004; E-mail: hfchow@cuhk.edu.hk
Abstract: A series of [G1] to [G3]-oligo(dibenzylsulfide) dendrimers containing up to 21 interior dibenzyl-
sulfide moieties was prepared as starting materials toward the syntheses of two new series of oligo(dibenzyl
sulfone) and oligo(phenylenevinylene) dendrimers using two different dendrimer-to-dendrimer conversion
strategies. The first strategy entailed the interior functionalization of the [G1] to [G3]-oligo(dibenzylsulfide)s
to the corresponding [G1] to [G3]-oligo(dibenzyl sulfone)s via hydrogen peroxide oxidation. Successful
conversions of up to 21 interior dibenzylsulfide moieties to the corresponding dibenzyl sulfone groups were
demonstrated. The second involved the skeletal rearrangements, also named as dendrimer metamorphosis,
of the [G1] and [G2]-oligo(dibenzyl sulfone) dendritic backbones to the corresponding [G1] and [G2]-oligo-
(phenylenevinylene)s dendrimers via the Ramberg-Ba¨cklund (RB) reaction. Up to nine RB rearrangements
on a dendrimer skeleton were realized and the conversion efficiency of each single RB rearrangement
reaction was found to be 96%.
Introduction
tions occur either on the dendrimer surface or on the dendron
focal point. On the other hand, direct syntheses of dendritic
macromolecules involving dendrimer-to-dendrimer transforma-
tions (i.e. post-dendrimerization modifications) are less known.
Under this synthetic strategy, the full dendritic framework is
first secured either by the divergent or convergent method. The
dendritic backbone (i.e. branch and/or branching juncture) is
then subsequently modified to afford the desired target den-
drimer. Hence, dendrimer-to-dendrimer transformations invari-
ably invoke functional group conversions in the interior of the
dendrimer, which present a formidable challenge to both
polymer and synthetic chemistry.5 Nonetheless, dendrimer-to-
dendrimer conversion is a powerful strategy because new
dendrimers can be made in those cases where the required
branching building blocks are difficult to prepare or do not
possess enough reactivity to be used in the iterative synthetic
constructions. A review of the literature showed that most
dendrimer-to-dendrimer conversions reported to date involved
solely interior functional group transformations.5 On the other
hand, dendrimer-to-dendrimer transformations utilizing den-
drimer backbone rearrangements have not been disclosed in the
literature. Herein we report a new synthesis of oligo(phen-
ylenevinylene) dendrimers 1 via multiple dendrimer backbone
rearrangements of oligo(dibenzyl sulfone) dendrimers 2 by the
Ramberg-Ba¨cklund (RB) reaction (Figure 1).6 We use the term
‘dendrimer metamorphosis’ to describe such an extensive
Dendritic macromolecules are now playing an important role
with emerging interest in synthetic chemistry, biomedical
technology, and material science.1 This unique structural motif
allows the orderly placement of a large number of functional
groups in close proximity inside a hyperbranched polymer
framework. As a result, such functionalities may act in a
synergistic manner and produce the so-called ‘dendritic effects’2
that are of prime interest in functional dendrimer chemistry.
Despite rapid advances in the potential applications of
dendrimers, their synthesis are still confined to the divergent3
or the convergent4 synthetic strategies that were devised more
than 10 years ago. Hence there is still an urgent need for newer
methods for dendrimer constructions. In the divergent method,
the dendritic framework is constructed from the interior core
toward the periphery. On the other hand, dendrimer is assembled
from the periphery toward the central core in the convergent
protocol. Both strategies rely on functional group transforma-
(1) For recent reviews on dendrimer chemistry, see: (a) Newkome, G. R.;
Moorefield, C. N.; Vo¨gtle, F. Dendrimers and Dendrons. Concepts,
Syntheses, Applications; Wiley-VCH: Weinheim, Germany, 2001. (b)
Stiriba, S.-E.; Frey, H.; Haag, R. Angew. Chem., Int. Ed. 2002, 41, 1329-
1334. (c) Fre´chet, J. M. J. J. Polym. Sci. Part A: Polym. Chem. 2003, 41,
3713-3725. (d) Boas, U.; Heegaard, P. M. H. Chem. Soc. ReV. 2004, 33,
43-63.
(2) Chow, H.-F.; Leung, C.-F.; Wang, G.-X.; Yang, Y.-Y. C. R. Chimie 2003,
6, 735-745.
(3) (a) Buhleier, E.; Wehner, W.; Vo¨gtle, F. Synthesis 1978, 155-158. (b)
Tomalia, D. A.; Baker, H.; Dewald, J. R.; Hall, M.; Kallos, G.; Martin, S.;
Roeck, J.; Ryder, J.; Smith, P. Polym. J. 1985, 17, 117-132. (c) Newkome,
G. R.; Baker, G. R. Org. Prep. Proced. Int. 1986, 18, 117-144.
(4) (a) Hawker, C.; Fre´chet, J. M. J. J. Chem. Soc., Chem. Commun. 1990,
1010-1013. (b) Hawker, C. J.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1990,
112, 7638-7647.
(5) For a review, see Hecht, S. J. Polym. Sc. Part A: Polym. Chem. 2003, 41,
1047-1058.
(6) For a recent review, see Taylor, R. J. K.; Casy, G. Org. React. 2003, 59,
357-475.
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J. AM. CHEM. SOC. 2004, 126, 12907-12915
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A R T I C L E S
Chow et al.
stereoselectivity from various sulfone precursors. This modified
procedure had been reported to suppress the formation of a
dihalocarbene-olefin adduct that was frequently formed as a side
product in the Meyers RB protocol.19 We disclose here that both
the [G1]-tri(phenylenevinylene) 4 and [G2]-nona(phenylene-
vinylene) 5 dendrimers can readily be prepared from the
corresponding [G1]-tri(sulfone) 6 and [G2]-nona(sulfone) 7
derivatives, respectively, via dendrimer metamorphosis. It should
be noted that three and nine molecular rearrangements are
involved in the transformation reactions of the [G1] and [G2]
dendrimers, respectively. To the best of our knowledge, multiple
RB rearrangements on a single molecule involving these many
processes have not been reported before. Unfortunately, despite
many attempts, we were unable to extend this dendrimer
metamorphosis strategy to the [G3]-series due to steric shielding
and heterogeneous nature of the RB reaction conditions. The
[G1] to [G3]-oligo(sulfone) dendrimers 6, 7, and 10, in turn,
were readily prepared by sulfide oxidation20 under homogeneous
reaction conditions from the corresponding [G1] to [G3]-oligo-
(sulfide) dendrimers 8, 9, and 11, respectively, via functional
group conversions occurred in the interior domain.
Figure 1. Interior functional group conversion from an oligo(dibenzylsul-
fide) dendrimer 3 to an oligo(dibenzyl sulfone) dendrimer 2 and dendrimer
metamorphosis of an oligo(dibenzyl sulfone) dendrimer 2 to an oligo-
(phenylenevinylene) dendrimer 1.
backbone rearrangement on a dendritic molecule since a new
type of dendrimer with a completely different backbone structure
is generated by this new strategy. We also show here that the
oligo(dibenzyl sulfone) dendrimers 2 can be prepared from
oligo(dibenzylsulfide) dendrimers 3 through dendrimer-to-
dendrimer conversions involving interior functional group
transformations. The scope and limitations of the dendrimer
interior functional group conversion and dendrimer metamor-
phosis are also discussed. These strategies are of particular
interest to the future synthetic design of dendrimers, post-
dendrimerization modifications and interior functionalizations
of dendrimers.
Oligo(phenylenevinylene) dendrimers7 and their derivatives
had been shown to possess interesting liquid crystalline,8
photophysical,8b,d,9-13 electrochemical,9c,d,10a-c,e and electrolu-
minescence properties.9a,d The stilbene skeleton was established
either by the Heck reaction between an aryl halide with a
vinylbenzene derivative,9a,b,10d,11,13 or by the Horner-Wad-
sworth-Emmons coupling between an aromatic aldehyde with
a benzylphosphonate.8,9,10c-e,12-14 With the exceptions of those
reported by Mart´ın10c and Mongin,12 the CdC bonds generated
from the above reactions were solely of (E)-configuration.
We previously demonstrated that the modified RB reaction
(KOH/Al2O3, CBr2F2, t-BuOH) reported by Chan15 could be
used to construct highly conjugated systems such as enediyne,16
1,3,5-hexatrienes,17 and 1,3,5,7-octatetraenes18 with good (E)-
(7) For a reveiw on oligo(phenylenevinylene) dendrimers, see Meier, H.;
Lehmann, M. In Encyclopedia of Nanoscience and Nanotechnology, Vol.
10; Nalwa, H. S., Ed.; American Scientific Publishers: California, 2004;
pp 95-106.
(8) (a) Meier, H.; Lehmann, M. Angew. Chem., Int. Ed. 1998, 37, 643-645.
(b) Lehmann, M.; Schartel, B.; Hennecke, M.; Meier, H. Tetrahedron 1999,
55, 13377-13394. (c) Meier, H.; Lehmann, M.; Kolb, U. Chem. Eur. J.
2000, 6, 2462-2469. (d) Lehmann, M.; Fischbach, I.; Spiess, H. W.; Meier,
H. J. Am. Chem. Soc. 2004, 126, 772-784.
(9) (a) Halim, M.; Pillow, J. N. G.; Samuel, I. D. W.; Burn, P. L. AdV. Mater.
1999, 11, 371-374. (b) Pillow, J. N. G.; Halim, M.; Lupton, J. M.; Burn,
P. L.; Samuel, I. D. W. Macromolecules 1999, 32, 5985-5993. (c) Pålsson,
L.-O.; Beavington, R.; Frampton, M. J.; Lupton, J. M.; Magennis, S. W.;
Markham, J. P. J.; Pillow, J. N. G.; Burn, P. L.; Samuel, I. D. W.
Macromolecules 2002, 35, 7891-7901. (d) Beavington, R.; Frampton, M.
J.; Lupton, J. M.; Burn, P. L.; Samuel, I. D. W. AdV. Funct. Mater. 2003,
13, 211-218.
(10) (a) D´ıez-Barra, E.; Garc´ıa-Mart´ınez, J. C.; Rodr´ıguez-Lo´pez, J.; Go´mez,
R.; Segura, J. L.; Mart´ın, N. Org. Lett. 2000, 2, 3651-3653. (b) Langa,
F.; Go´mez-Escalonilla, M. J.; D´ıez-Barra, E.; Garc´ıa-Mart´ınez, J. C.; de la
Hoz, A.; Rodr´ıguez-Lo´pez, J.; Gonza´lez-Corte´s, A.; Lo´pez-Arza, V.
Tetrahedron Lett. 2001, 42, 3435-3438. (c) Segura, J. L.; Go´mez, R.;
Mart´ın, N.; Guldi, D. M. Org. Lett. 2001, 3, 2645-2648. (d) D´ıez-Barra,
E.; Garc´ıa-Mart´ınez, J. C.; Merino, S.; del Rey, R.; Rodr´ıguez-Lo´pez, J.;
Sa´nchez-Verdu´, P.; Tejeda, J. J. Org. Chem. 2001, 66, 5664-5670. (e)
D´ıez-Barra, E.; Garc´ıa-Mart´ınez, J. C.; del Rey, R.; Rodr´ıguez-Lo´pez, J.;
Giacalone, F.; Segura, J. L.; Mart´ın, N. J. Org. Chem. 2003, 68, 3178-
3183.
Results and Discussion
Synthesis of [G1] to [G3]-Oligo(dibenzylsulfide) Dendrim-
ers. The [G1] to [G3]-oligo(sulfide) dendrimers 8, 9, and 11
consist of four structural components: the surface sector, the
linker, the branching unit, and the central core. An n-hexyl group
was chosen as the surface unit, which was required to improve
the solubility property of the dendrimers and to facilitate their
structural characterizations. The linker used was a -CH2SCH2-
(11) Sengupta, S.; Sadhukhan, S. K.; Singh, R. S.; Pal, N. Tetrahedron Lett.
2002, 43, 1117-1121.
(12) Mongin, O.; Brunel, J.; Porre`s, L.; Blanchard-Desce, M. Tetrahedron Lett.
2003, 44, 2813-2816.
(13) Deb, S. K.; Maddux, T. M.; Yu, L. J. Am. Chem. Soc. 1997, 119, 9079-
9080.
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A R T I C L E S
methoxide in a mixture of THF and MeOH to give the
corresponding thiol 18. The choice of the solvent was crucial
for the success of this reaction. In the absence of MeOH, the
rate of acetyl cleavage was too slow as sodium methoxide was
only slightly soluble in THF. On the other hand, the thiolacetate
12 was not soluble in pure MeOH and hence a mixture of MeOH
and THF was required to facilitate the transformation. Thin layer
chromatographic (TLC) analysis of the reaction mixture indi-
cated the coupling reaction was very fast, and was completed
in 3 min at 25 °C. Strict exclusion of oxygen during the coupling
reaction was also important as the thiol 18 was highly
susceptible to self-oxidation to give a disulfide that was difficult
to separate from the target [G1]-tri(sulfide) 8. Therefore the thiol
18 was generated in situ and immediately coupled to the
trifunctional core 13 to give the target [G1]-tri(sulfide) 8 in 83%
as colorless oil after chromatography.
To obtain the [G2]-series of compounds, the thiol 18 (2 equiv)
was reacted with methyl 3,5-bis(bromomethyl)benzoate 14 to
give the [G2]-methyl ester dendron 19 in 92% yield (Scheme
2). The methyl ester 19 was reduced to the corresponding benzyl
alcohol 20 by LAH followed by functional group conversion
(CH3COSH/PPh3/DIAD) to produce the [G2]-thiolacetate 21 in
an overall 77% yield. Finally, 3 equiv of the thiolacetate 21
was linked to the trifunctional core 13 to furnish the [G2]-nona-
(sulfide) dendrimer 9 in 78% yield after chromatographic
purification.
Figure 2. Retrosynthetic analysis of the [G2]-oligo(dibenzylsulfide)
dendrimer 9.
unit, which was already endowed with the structural element
for its future transformation to the stilbene functionality. Both
the branching juncture and the central core employed were a
1,3,5-phenylene unit. A retrosynthetic analysis on the [G2]-
oligo(dibenzylsulfide) dendrimer 9 suggested that such den-
drimers could be assembled from three basic components: 3,5-
di-(n-hexyl)benzylthiolacetate 12 as the surface unit, 1,3,5-
tris(bromomethyl)benzene 1314 as the central core, and methyl
3,5-bis(bromomethyl)benzoate 1421 as the branching propagating
unit (Figure 2).
The convergent synthetic approach was used to assemble the
target oligo(sulfide) dendrimers. Hence, Sonogashira coupling22
between 1-hexyne (4 equiv) and commercially available methyl
3,5-dibromobenzoate afforded the bis(acetylene) adduct 15 as
a yellow oil in 85% yield (Scheme 1). The triple bonds were
then hydrogenated in the presence of 10% Pd/C in absolute
EtOH at 25 °C to give the di-n-hexyl substituted benzoate 16
(95%) as an oil. The methyl ester 16 was subsequently reduced
by lithium aluminum hydride (LAH) in THF to give the
corresponding benzyl alcohol 17 in 95% yield. Finally, reaction
of the alcohol 17 with thiolacetic acid in the presence of
triphenylphosphine (PPh3) and diisopropyl azodicarboxylate
(DIAD) produced the benzylthiolacetate 12 in 87% yield. The
structure and purity of all the dendrons described above were
confirmed by 1H and 13C NMR, mass spectroscopy, and
elemental analyses.
The syntheses of the various [G3]-dendrons and [G3]-
heneicos(sulfide) dendrimer 11 were similarly accomplished by
using the same synthesis sequence. Hence, coupling of the [G2]-
thiolacetate 21 (2.0 equiv) with the branching unit 14 in the
presence of sodium methoxide gave the desired [G3]-ester
dendron 22 in 78% yield (Scheme 3). Reduction of the ester
22 with LAH then afforded the [G3]-benzyl alcohol 23 in 87%
yield. The alcohol 23 was then converted to the corresponding
thiolacetate 24 in 76% yield under the Mitsunobu conditions
(CH3COSH/PPh3/DIAD). Anchorage of the [G2]-thiolacetate 24
to the central core 13, however, turned out to be relatively slow
(∼1 h) and this could be due to steric inhibition at the focal
point thiol functionality. Nonetheless, the desired [G3]-heneicos-
(sulfide) 11 could be obtained in 66% yield after chromato-
graphic purification.
The structural identities of the various [G2] and [G3]-
dendrons as well as the target oligo(sulfide)s 8, 9, and 11 were
determined by 1H, 13C NMR, and mass spectroscopy. The layer
architecture of the oligo(sulfide) dendrimers can be clearly
revealed from their 1H NMR spectra. Hence the aromatic protons
of the central core appeared as a singlet at around ∼δ 7.1 for
all three generations of dendrimer, while those of the surface
aromatic branching units were located as two sets of singlet at
∼δ 6.9. On the other hand, the proton signals of the aromatic
branching units situated in the intermediate layer(s) were found
to situate between δ 7.17 and 7.07 (Table 1). While the relative
integration values obtained from 1H NMR spectroscopy is very
useful in ascertaining the structure of the lower generation [G1]-
and [G2]-series of compounds, it alone cannot provide conclu-
sive evidence for those of the higher generation [G3] compounds
as the relative integration of the central core aromatic protons
now became relatively small to be measured accurately. Hence,
MS and SEC data were also obtained to confirm their structure
and homogeneity. Using MALDI-TOF MS analysis, the mo-
For the synthesis of the [G1]-tri(sulfide) 8, the acetyl group
of the thiolacetate 12 was removed in the presence of sodium
(14) D´ıez-Barra, E.; Garc´ıa-Mart´ınez, J. C.; Rodr´ıguez-Lo´pez, J. Tetrahedron
Lett. 1999, 40, 8181-8184.
(15) Chan, T.-L.; Fong, S.; Li, Y.; Man, T.-O.; Poon, C.-D. J. Chem. Soc., Chem.
Commun. 1994, 1771-1772.
(16) Cao, X.-P.; Chan, T.-L.; Chow, H.-F. Tetrahedron Lett. 1996, 37, 1049-
1052.
(17) Cao, X.-P.; Chan, T.-L.; Chow, H.-F.; Tu, J. J. Chem. Soc., Chem. Commun.
1995, 1297-1299.
(18) Cao, X.-P. Tetrahedron 2002, 58, 1301-1307.
(19) Meyers, C. Y.; Malte, A. M.; Matthews, W. S. J. Am. Chem. Soc. 1969,
91, 7510-7512.
(20) The direct oxidation of linear poly(sulfide) polymers to their corresponding
poly(sulfone) polymers had been reported in the literature, see Marvel, C.
S.; Weil, E. D. J. Am. Chem. Soc. 1954, 76, 61-69.
(21) Markovac, A.; LaMontagne, M. P. J. Med. Chem. 1980, 23, 1198-1201.
(22) Takahashi, S.; Kuroyama, Y.; Sonogashira, K.; Hagihara, N. Synthesis 1980,
627-630.
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A R T I C L E S
Chow et al.
Scheme 1. Synthesis of Surface Unit 12 and [G1]-Tri(sulfide) Dendrimer 8a
a (i) 1-hexyne (4 equiv), Pd(PPh3)2Cl2, CuI, NEt3, C6H6, 80 °C, 48 h; (ii) H2, 10% Pd/C, EtOH, 25 °C, 18 h; (iii) LiAlH4, THF, 0-25 °C, 1 h; (iv)
CH3COSH, DIAD, PPh3, THF, 0-25 °C, 2 h; (v) NaOMe, MeOH, THF, 25 °C, 5 min; (vi) 1,3,5-tris(bromomethyl)benzene (0.3 equiv), MeOH, THF, 25
°C, 1 h.
Scheme 2. Synthesis of [G2]-Dendrons and [G2]-Nona(sulfide)
oligo(sulfide)s. In the absence of CH2Cl2, the partially oxidized
species containing both sulfoxide and sulfone oxidation states
Dendrimer 9a
tended to precipitate from the reaction medium and further
oxidation of the remaining sulfoxide moieties would stop to
proceed. By using this procedure, the [G1] 8, [G2] 9, and [G3]-
oligo(sulfide)s 11 could be successfully converted to the [G1]-
tri(sulfone) 6 (95%), [G2]-nona(sulfone) 7 (64%), and [G3]-
heneicos(sulfone) 10 (51%), respectively.
The 1H NMR spectroscopic data of the oligo(sulfone)s
revealed one interesting feature of these species in solution
1
(Table 2). Upon oxidation, the H aromatic signals due the
central core and the surface aromatic rings were slightly
downfield shifted (∼0.2 ppm). On the other hand, the corre-
sponding signals originated from the intermediate branching
aromatic ring(s) experienced a significantly large downfield shift
a (i) NaOMe, MeOH, THF, 25 °C, 5 min; (ii) methyl 3,5-bis(bromo-
methyl)benzoate 14 (0.5 equiv), MeOH, THF, 25 °C, 1 h; (iii) LiAlH4,
THF, 0-25 °C, 1 h; (iv) CH3COSH, DIAD, PPh3, THF, 0-25 °C, 2 h; (v)
1,3,5-tris(bromomethyl)benzene (0.3 equiv), MeOH, THF, 25 °C, 1 h.
of ∼0.7 ppm. However, there was little difference between the
chemical shifts of the core and intermediate branching aromatic
protons in the corresponding oligo(sulfide) series. We speculated
that the presence of many strong sulfone-oxygen dipoles favored
the oligo(sulfone)s to adopt a conformation wherein the aromatic
rings in the intermediate layer were experiencing a strong
lecular peaks found for the [G1], [G2], and [G3]-oligo(sulfide)s
were at 1097.5 (M + Ag+), 2421.3 (M + Ag+), and 5064.4 (M
deshielding effect from another aromatic moieties. Furthermore,
+ Ag+), respectively. Their SEC chromatograms also revealed
the presence of one major peak with a polydispersity index of
less than 1.04.
1
the H benzylic signals adjacent to the sulfone moieties in all
three generations of oligo(sulfone) were downfield shifted to
∼δ 4.1-4.3. We could not detect any products due to partial
Interior Functional Group Transformations-Oligo
oxidation to the sulfoxide state as no signals was found in the
(dibenzylsulfide) to Oligo(dibenzoyl sulfone) Dendrimers.
The [G1] to [G3] oligo(sulfide) dendrimers 8, 9, and 11 were
then converted to the corresponding oligo(sulfone)s 6, 7, and
10, respectively, by oxidation reactions of all the sulfide
region (∼δ 3.9) normally ascribed to benzylic signals adjacent
to a dibenzylsulfoxide skeleton. Due to the relatively poor
solubility of the [G3]-heneicos(sulfone) 10 in CDCl3, the
1
aliphatic H NMR signals were partly masked by the residue
functionalities located in the interior domain. Initial trials on
water signal in the solvent. Therefore, accurate integration values
the [G1]-tri(sulfide) 8 employing oxone23 as the oxidizing agent
in this region could not be obtained but its layered structure
either in MeOH or in CH2Cl2 were unsuccessful. The reaction
could be clearly revealed by examining the 1H NMR signals in
time was long (>48 h) and the conversion was poor. It was
the aromatic region. Furthermore, the conversion of all the
later found that the use of 35% H2O2 in a boiling mixture of
sulfide moieties to the corresponding sulfone groups could be
acetic acid and CH2Cl2 proved to be highly effective in
confirmed from MALDI-TOF MS analysis. In all cases, the
converting all the sulfides to the corresponding sulfone moieties
molecular ion found was due to the (M + Ag)+ species. We
(Scheme 4). Apart from the [G1]-tri(sulfone) 6, the higher
could not identify any mass peaks with m/z value of (M - 16)+,
generation [G2] and [G3]-oligo(sulfone)s obtained are highly
(M - 32)+, or (M - 48)+ that were due to the incompletely
crystalline materials and have poor solubility24 except in large
oxidized sulfoxide species (Figure 3). The structural purity of
amount of chlorinated solvents or THF. The addition of CH2-
the [G1] to [G3]-oligo(sulfone)s was also examined by SEC
Cl2 was essential in promoting the complete oxidation of the
analysis. In all cases, a major peak was identified in the SEC
chromatogram although it was slightly broaden as compared to
that of the corresponding oligo(sulfide) analogue.
Dendrimer Metamorphosis-Synthesis of Oligo(phen-
ylenevinylene) Dendrimers. The [G1]-tri(sulfone) 6 was then
(23) Trost, B. M.; Curran, D. P. Tetrahedron Lett. 1981, 22, 1287-1290.
(24) Linear poly(sulfone)s were reported to be highly crystalline and possess
poor solubility, see: (a) Macro, C.; Bello, A.; Peren˜a, J. M.; Fatou, J. G.
Macromolecules 1983, 16, 95-99. (b) Lee, J.-C.; Litt, M. H.; Rogers, C.
E. Macromolecules 1997, 30, 3766-3774.
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A R T I C L E S
Scheme 3. Synthesis of [G3]-Dendrons and [G3]-Heneicos(sulfide) Dendrimer 11a
a (i) NaOMe, MeOH, THF, 25 °C, 5 min; (ii) methyl 3,5-bis(bromomethyl)benzoate (0.5 equiv), MeOH, THF, 25 °C, 1 h; (iii) LiAlH4, THF, 0-25 °C,
1 h; (iv) CH3COSH, DIAD, PPh3, THF, 0-25 °C, 2 h; (v) 1,3,5-tris(bromomethyl)benzene (0.3 equiv), MeOH, THF, 25 °C, 1 h.
Table 1. Selected 1H NMR Chemical Shift Values of Oligo(sulfide) Dendrimers 8, 9, and 11a,b
dendrimer
core ArH
intermediate ArH
surface ArH
−CH2SCH2−
[G1]-tri(sulfide) 8
[G2]-nona(sulfide) 9
[G3]-heneicos(sulfide) 11
7.13 (3)
7.11 (3)
7.12 (3)
-
6.93 (6), 6.88 (3)
6.95 (12), 6.90 (6)
6.91 (24), 6.86 (12)
3.59 (6), 3.57 (6)
3.60 (18), 3.58 (18)
3.58 (12), 3.56 (48), 3.54 (24)
7.17 (9)
7.16 (9), 7.13 (12), 7.07 (6)
a In CDCl3. b Number in parentheses indicates number of protons.
Table 2. Selected 1H NMR Chemical Shift Values of Oligo(sulfone) Dendrimers 6, 7, and 10a,b
dendrimer
core ArH
intermediate ArH
surface ArH
−CH2SO2CH2−
[G1]-tri(sulfone) 6
[G2]-nona(sulfone) 7
[G3]-heneicos(sulfone) 10
7.38 (3)
7.35 (3)
7.32 (3)
-
7.04 (9)
7.07 (12), 7.04 (6)
7.04 (24), 7.01 (12)
4.16 (6), 4.08 (6)
4.31 (12), 4.28 (6), 4.19 (18)
4.42 (6), 4.37 (6), 4.23 (24), 4.19 (24), 4.16 (24)
7.83 (6), 7.81 (3)
7.86 (3), 7.71 (6), 7.69 (12), 7.32 (6)
a In CDCl3. b Number in parentheses indicates number of protons.
Scheme 4. Interior Functional Group Conversionsa
consistent with those observed for primary dibenzylic sulfones
reported earlier.15
Reaction of the [G2]-nona(sulfone) 7 under similar conditions
afforded the corresponding [G2]-nona(phenylenevinylene) den-
drimer 5 (72% yield) at -45 °C. To our surprise, the CdC
bonds formed are of both (E)- and (Z)-configurations. Hence,
the (E)-stereoselectivity of the RB reaction decreased in the case
of the G2 dendrimer. Nonetheless, the all (E)-[G2]-nona-
(phenylenevinylene) isomer 5 could be isolated as the major
product in 48% yield after careful silica gel chromatography.
The (E)- and (Z)-percentage distributions of the remaining
a (i) 35% H2O2, HOAc, CH2Cl2, 40 °C, 6 h.
subjected the RB rearrangement reaction using Chan’s modified
conditions (KOH/Al2O3, CBr2F2) in t-BuOH.15 However, the
reaction was too slow and sluggish. After several experimenta-
tions, it was found that a mixture of THF and t-BuOH was a
better solvent system for the reaction as the oligo(sulfone)
dendrimers were found to have slightly better solubility (Scheme
5). Under the new conditions, rearrangements of all three sulfone
moieties proceeded smoothly even at -45 °C. The reaction was
found to complete in 10 min and the all (E)-[G1]-tri(phen-
ylenevinylene) dendrimer 4 could be isolated in 91% yield. The
(E)-configuration of the newly formed double bonds was
confirmed by the large coupling constant (J ) 16.5 Hz) between
1
mixture (24%) of isomers could not be ascertained from H
NMR spectroscopy. Since there are nine independent RB
rearrangements on this molecule, the conversion efficiency of
each RB rearrangement is therefore 96%. This value is and has
to be extremely high in order to produce the target dendrimer
in good yields, as one single failure out of the nine rearrange-
ments would completely ruin the dendrimer metamorphosis
process. Both the pure all (E)-isomer 5 and the geometrical
mixtures could be separately converted to the same saturated
[G2]-nona(phenyleneethylene) dendrimer 25 in 78% and 82%
yield, respectively, by catalytic hydrogenation (10% Pd/C, CH2-
Cl2, EtOH).
1
the olefinic protons in its H NMR spectrum. There were no
1
other isomeric products found according to H NMR analysis.
The high (E)-stereoselectivity of the modified RB reaction was
9
J. AM. CHEM. SOC. VOL. 126, NO. 40, 2004 12911

A R T I C L E S
Chow et al.
presence of residual benzylic protons at ∼δ 4.1-4.3, indicating
1
that some of the sulfone groups remained unreacted. The H
NMR signals in the aromatic and olefinic regions (δ 7.8-6.7)
were very broad and complex, suggesting the CdC bonds
formed were of both (E)- and (Z)-configurations. Hence, the
products were a mixture of partially converted RB reaction
products that still contained some unreacted dibenzylic sulfone
moieties. However, no further transformations took place even
when the crude product was re-subjected to the same RB
rearrangement conditions. Despite numerous attempts by chang-
ing the reagents, the reaction solvents and temperature, a
complex mixture of similar 1H NMR signal profile was always
formed.
We believed the failure to effect the dendrimer metamorphosis
with the [G3]-heneicos(sulfone) 10 was attributed to both steric
shielding and the heterogeneous reaction conditions. Since
potassium hydroxide was impregnated on alumina and had a
limited solubility in THF/t-BuOH, therefore the interior sulfone
moieties may have difficulty in undergoing deprotonation to
initiate the first step of the RB rearrangement. Furthermore, once
the sulfone moieties near the dendrimer surface have been
converted into the corresponding stilbene functionalities, the
dendrimer skeleton will become more compact as the dendrimer
branch has now changed from a three-atom to a two-atom
spacer. This could lead to the encapsulation of the interior
sulfone moieties and prevented them from reactions. It should
be pointed out that the rearrangement reactions involving all
21 sulfone moieties were very similar to those reactions in the
divergent dendrimer synthetic approach; both of which required
a large number of reactions to take place on a molecular species.
The results of Meijer’s work on the synthesis of poly(propylene
imine) dendrimers had already illustrated that even with highly
optimized reaction conditions, the production of defect-free
products was impossible to achieve by the divergent synthetic
procedure.25 An additional complicated factor in our situation
was that the rearrangement reactions had to take place not on
the periphery, but inside the interior of the dendrimer, and was
therefore sterically more demanding than the divergent growth
on a dendrimer surface.
Figure 3. MALDI-TOF mass spectra of oligo(sulfone) dendrimers [G1] 6
(top), [G2] 7 (middle), and [G3] 10 (bottom).
Scheme 5. Dendrimer Metamorphosisa
Experimental Section
Materials and General Methods. Melting points were determined
on an Electrothermal IA9000 apparatus and were uncorrected. Nuclear
magnetic resonance (NMR) spectra were recorded on a Bru¨ker Avance
DPX300 spectrometer (1H: 300 MHz; 13C: 75.5 MHz) in CDCl3. Mass
spectra were obtained on a HP 5989 mass spectrometer by electron
ionization (EI) or a home-built time-lag focusing matrix-assisted laser
desorption ionization (MALDI) mass spectrometer. Saturated AgNO3/
EtOH was added as the cationization reagent. The reported molecular
mass (m/z) values were the most abundant monoisotopic mass. UV
spectra were recorded on a Hitachi U-3300 spectrophotomer at 27 °C
using spectroscopic grade CHCl3 as the solvent. SEC (Waters Styragel
HR4, HR3, HR2, and HR1 columns in series) measurements were
carried out in THF at 40 °C on a Waters HPLC 510 pump equipped
with a Waters 486 tunable UV absorbance detector. Elemental analyses
were carried out either at MEDAC Ltd., UK, or at Shanghai Institute
of Organic Chemistry, China. All reagents were purchased from
commercial suppliers (Acros or Aldrich) and used without further
purification. All reactions were performed under N2 atmosphere unless
otherwise noted. Thin-layer chromatography (TLC) was performed on
a (i) KOH/Al2O3, CBr2F2, THF, t-BuOH, -45 °C, 10 min; (ii) H2, 10%
Pd/C, CH2Cl2, EtOH, 25 °C, 48 h.
Rearrangement of the [G3]-heneicos(sulfone) 10 under similar
reaction conditions, however, failed to produce the target [G3]-
heneicos(phenylenevinylene). TLC analysis of the crude reaction
suggested the formation of many inseparable reaction products.
(25) Hummelen, J. C.; van Dongen, J. L. J.; Meijer, E. W. Chem. Eur. J. 1997,
3, 1489-1493.
1
Further examination by H NMR spectroscopy revealed the
9
12912 J. AM. CHEM. SOC. VOL. 126, NO. 40, 2004

Dendrimer Metamorphosis
A R T I C L E S
silica gel sheets 60 F254 (E. Merck). Flash chromatography was
performed on silica gel (Macherey Nagel Kieselgel 60M 230-400
mesh).
22.6, 14.1; SEC retention time: 32.15 min. Anal. Calcd for C103H152
OS6: C, 77.38; H, 9.58. Found: C, 77.65; H, 9.43.
-
General Procedure for the Synthesis of Dendritic Thiolacetates
[Gn]-CH2SAc (n ) 1-3). DIAD (2.0 mol. equiv) was added to a
solution of triphenylphosphine (2.0 mol. equiv) in dry THF at 0 °C.
After 10 min, a solution of the dendritic alcohol [Gn]-CH2OH (1.0
mol. equiv) and thiolacetic acid (2.0 mol. equiv) in dry THF was then
added and the reaction mixture was stirred at 25 °C for 2 h. Hexane
was added to precipitate the triphenylphosphine oxide formed. The
reaction mixture was filtered through a short pad of silica gel and the
filtrate was concentrated in vacuo. The crude product was purified by
silica gel chromatography (hexane/EtOAc ) 30/1) to afford the desired
product.
[G1]-CH2SAc (12). Starting from [G1]-CH2OH 17 (5.10 g, 18.4
mmol), [G1]-CH2SAc 12 (5.86 g, 87%) was obtained as a colorless
oil; Rf 0.75 (hexane/EtOAc ) 10/1); 1H NMR: 6.93 (s, 2 H), 6.90 (s,
1 H), 4.11 (s, 2 H), 2.57 (t, J ) 7.7 Hz, 4 H), 2.37 (s, 3 H), 1.68-1.50
(m, 4 H), 1.40-1.25 (m, 12 H), 0.92 (t, J ) 6.5 Hz, 6 H); 13C NMR:
195.2, 143.2, 137.0, 127.6, 126.1, 35.8, 33.5, 31.7, 31.4, 30.2, 29.0,
22.6, 14.1; MS (EI, m/z): 335 (M+, 22%). Anal. Calcd for C21H34OS:
C, 75.39; H, 10.24. Found: C, 75.49; H, 10.48.
[G2]-CH2SAc (21). Starting from [G2]-CH2OH 20 (4.40 g, 6.1
mmol), [G2]-CH2SAc 21 (3.97 g, 83%) was obtained as a colorless
oil; Rf 0.70 (hexane/EtOAc ) 10/1); 1H NMR: 7.15 (s, 1 H), 7.10 (s,
2 H), 6.94 (s, 4 H), 6.90 (s, 2 H), 4.11 (s, 2 H), 3.58 (s, 8 H), 2.58 (t,
J ) 7.7 Hz, 8 H), 2.37 (s, 3 H), 1.70-1.55 (m, 8 H), 1.40-1.25 (m,
24 H), 0.90 (t, J ) 6.6 Hz, 12 H); 13C NMR: 194.8, 143.0, 139.0,
137.7, 137.6, 128.6, 128.0, 127.3, 126.4, 35.9, 35.8, 35.4, 33.3, 31.7,
31.5, 30.3, 29.1, 22.6, 14.1; SEC retention time: 34.14 min; MS
(MALDI-TOF, m/z): 881.4 (M + Ag+). Anal. Calcd for C49H74OS3:
C, 75.91; H, 9.62. Found: C, 75.86; H, 9.86.
[G3]-CH2SAc (24). Starting from [G3]-CH2OH 23 (2.50 g, 1.56
mmol), the [G3]-CH2SAc 24 (1.96 g, 76%) was obtained as a colorless
oil; Rf 0.71 (hexane/EtOAc ) 10/1); 1H NMR: 7.16 (s, 1 H), 7.12 (s,
4 H), 7.10 (s, 2 H), 7.08 (s, 2 H), 6.92 (s, 8 H), 6.87 (s, 4 H), 4.08 (s,
2 H), 3.59 (s, 8 H), 3.57 (s, 8 H), 3.56 (s, 4 H), 3.54 (s, 4 H), 2.55 (t,
J ) 7.8 Hz, 16 H), 2.32 (s, 3 H), 1.68-1.50 (m, 16 H), 1.40-1.22 (m,
48 H), 0.88 (t, J ) 6.6 Hz, 24 H); 13C NMR: 194.9, 143.0, 138.81,
138.76, 138.4, 138.0, 137.5, 128.7, 128.5, 128.4, 128.2, 127.3, 126.4,
35.9, 35.8, 35.5, 35.4, 35.3, 33.2, 31.7, 31.5, 30.3, 29.1, 22.6, 14.1;
SEC retention time: 32.08 min; MS (MALDI-TOF, m/z): 1761.5 (M
+ Ag+). Anal. Calcd for C105H154OS7: C, 76.12; H, 9.37. Found: C,
75.76; H, 9.33.
Methyl 3,5-Di-(hex-1-ynyl)benzoate (15). A mixture of methyl 3,5-
dibromobenzoate (7.35 g, 25 mmol), 1-hexyne (11.0 mL, 100 mmol),
bis(triphenylphosphine)palladium(II) dichloride (1.40 g, 2.0 mmol),
copper(I) iodide (0.19 g, 1.0 mmol), and triethylamine (20 mL) in dry
benzene (80 mL) was heated at 80 °C for 48 h. The mixture was filtered
through a short pad of silica gel and washed with ethyl acetate (200
mL). The solvent was concentrated in vacuo and the residue chro-
matographed on silica gel (hexane/CH2Cl2 ) 8/1) to give compound
1
15 (6.30 g, 85%) as a yellow oil; Rf 0.25 (hexane/CH2Cl2 ) 8/1); H
NMR: 7.92 (d, J ) 1.5 Hz, 2 H), 7.56 (t, J ) 1.5 Hz, 1 H), 3.89 (s,
3 H), 2.39 (t, J ) 6.6 Hz, 4 H), 1.60-1.40 (m, 8 H), 0.94 (t, J ) 7.2
Hz, 6 H); 13C NMR: 166.0, 138.4, 131.4, 130.3, 124.6, 91.8, 79.1,
52.2, 30.6, 21.9, 19.0, 13.6; MS (EI, m/z): 296 (M+, 64%). Anal. Calcd
for C20H24O2: C, 81.04; H, 8.16. Found: C, 80.98; H, 7.98.
Methyl 3,5-Di-(n-hexyl)benzoate (16). A mixture of compound 15
(6.30 g, 21 mmol) and 10% Pd/C (1.0 g) in absolute EtOH (60 mL)
was stirred under hydrogen at atmospheric pressure at 25 °C. After 18
h, the mixture was filtered through a pad of Celite. The filtrate was
concentrated in vacuo and the residue chromatographed on silica gel
(hexane/EtOAc ) 15/1) to give compound 16 (6.13 g, 95%) as a
1
colorless oil; Rf 0.57 (hexane/EtOAc ) 10/1); H NMR: 7.68 (s, 2
H), 7.18 (s, 1 H), 3.90 (s, 3 H), 2.62 (t, J ) 8.2 Hz, 4 H), 1.70-1.55
(m, 4 H), 1.40-1.25 (m, 12 H), 0.88 (t, J ) 6.6 Hz, 6 H); 13C NMR:
167.4, 143.0, 133.2, 129.9, 126.8, 51.8, 35.7, 31.6, 31.3, 28.9, 22.5,
14.0; MS (EI, m/z): 305 (M + H+, 100%). Anal. Calcd for C20H32O2:
C, 78.90; H, 10.59. Found: C, 78.95; H, 10.47.
General Procedure for the Synthesis of Benzyl Alcohols [Gn]-
CH2OH (n ) 1-3). Powdered lithium aluminum hydride (1.1 mol.
equiv) was added in small portions to a solution the dendritic methyl
ester [Gn]-CO2Me (1.0 mol. equiv) in dry THF at 0 °C. The mixture
was allowed to stir at 25 °C. The reaction progress was monitored by
TLC until all the starting material disappeared (∼1 h). The excess
hydride was quenched by the addition of ice water. The product was
extracted with ethyl acetate and dried (MgSO4). The organic solvent
was filtered and concentrated in vacuo. The residue was chromato-
graphed on silica gel (hexane/EtOAc ) 15/1) to give the target
compound.
[G1]-CH2OH (17). Starting from [G1]-CO2Me 16 (6.00 g, 19.7
mmol), compound [G1]-CH2OH 17 (5.18 g, 95%) was obtained as a
colorless oil; Rf 0.31 (hexane/EtOAc ) 6/1); 1H NMR: 7.02 (s, 2 H),
6.96 (s, 1 H), 4.63 (d, J ) 5.7 Hz, 2 H), 2.61 (t, J ) 7.5 Hz, 4 H), 2.13
(t, J ) 5.7 Hz, 1 H), 1.70-1.55 (m, 4 H), 1.45-1.27 (m, 12 H), 0.93
(t, J ) 6.6 Hz, 6 H); 13C NMR: 143.1, 140.7, 127.8, 124.3, 65.4, 35.9,
31.7, 31.5, 29.1, 22.6, 14.1; MS (EI, m/z): 276 (M+, 58%). Anal. Calcd
for C19H32O: C, 82.55; H, 11.67. Found: C, 82.48; H, 11.56.
[G2]-CH2OH (20). Starting from [G2]-CO2Me 19 (4.84 g, 6.5
mmol), compound [G2]-CH2OH 20 (4.42 g, 93%) was obtained as a
colorless oil; Rf 0.25 (hexane/EtOAc ) 6/1); 1H NMR: 7.17 (s, 3 H),
6.93 (s, 4 H), 6.89 (s, 2 H), 4.67 (s, 2 H), 3.61 (s, 4 H), 3.59 (s, 4 H),
2.57 (t, J ) 7.8 Hz, 8 H), 1.70 (s, 1 H), 1.68-1.52 (m, 8 H), 1.42-
1.23 (m, 24 H), 0.90 (t, J ) 6.6 Hz, 12 H); 13C NMR: 143.0, 141.3,
138.9, 137.5, 128.9, 127.3, 126.4, 126.1, 65.1, 35.91, 35.86, 35.6, 31.7,
31.5, 29.1, 22.6, 14.1; SEC retention time: 34.11 min; MS (MALDI-
TOF, m/z): 823.4 (M + Ag+). Anal. Calcd for C47H72OS2: C, 78.71;
H, 10.12. Found: C, 78.62; H, 10.47.
[G3]-CH2OH (23). Starting from [G3]-CO2Me 22 (2.77 g, 1.7
mmol), compound [G3]-CH2OH 23 (2.58 g, 87%) was obtained as a
colorless oil; Rf 0.22 (hexane/EtOAc ) 6/1); 1H NMR: 7.23 (s, 1 H),
7.14 (s, 6 H), 7.12 (s, 2 H), 6.95 (s, 8 H), 6.91 (s, 4 H), 4.63 (s, 2 H),
3.61 (s, 8 H), 3.60 (s, 16 H), 2.58 (t, J ) 7.8 Hz, 16 H), 1.92 (s, 1 H),
1.70-1.54 (m, 16 H), 1.42-1.25 (m, 48 H), 0.91 (t, J ) 6.7 Hz, 24
H); 13C NMR: 143.0, 141.5, 138.7, 138.6, 138.4, 137.5, 128.8, 128.4,
128.3, 127.3, 126.4, 126.3, 64.8, 35.8, 35.5, 35.4, 35.3, 31.7, 31.5, 29.1,
General Procedure for the Synthesis of Dendritic Methyl Ester
[Gn]-CO2Me (n ) 2 and 3). Powdered sodium methoxide (2.4 mol.
equiv) was added in one portion to a stirred solution of the thiolacetate
[Gn]-CH2SAc (2.2 mol. equiv) in THF/CH3OH (v/v ) 1/1) at 25 °C.
After 5 min, methyl 3,5-bis(bromomethyl)benzoate 14 (1.0 mol. equiv)
in dry THF was added and the mixture was stirred for 1 h. The mixture
was concentrated and the residue was extracted with EtOAc. The
extracts were dried (MgSO4), filtered and the solvent was removed
under reduced pressure. The crude product was purified by silica gel
chromatography (hexane/EtOAc ) 30/1) to give the target compound.
[G2]-CO2Me (19). Starting from [G1]-CH2SAc 12 (5.80 g, 17.3
mmol), [G2]-CO2Me 19 (5.30 g, 92%) was isolated as a colorless oil;
1
Rf 0.52 (hexane/EtOAc ) 10/1); H NMR: 7.86 (s, 2 H), 7.46 (s, 1
H), 6.93 (s, 4 H), 6.90 (s, 2 H), 3.94 (s, 3 H), 3.63 (s, 4 H), 3.57 (s, 4
H), 2.57 (t, J ) 7.1 Hz, 8 H), 1.70-1.52 (m, 8 H), 1.42-1.25 (m, 24
H), 0.90 (t, J ) 6.6 Hz, 12 H); 13C NMR: 166.6, 143.0, 139.1, 137.3,
134.0, 130.4, 128.7, 127.3, 126.3, 52.0, 35.8, 35.7, 35.1, 31.7, 31.4,
29.0, 22.6, 14.1; SEC retention time: 34.21 min; MS (MALDI-TOF,
m/z): 851.2 (M + Ag+). Anal. Calcd for C48H72O2S2: C, 77.36; H,
9.74. Found: C, 77.21; H, 9.96.
[G3]-CO2Me (22). Starting from [G2]-CH2SAc 21 (3.80 g, 4.9
mmol), [G3]-CO2Me 22 (2.82 g, 78%) was obtained as a colorless oil;
1
Rf 0.49 (hexane/EtOAc ) 10/1); H NMR: 7.83 (s, 2 H), 7.46 (s, 1
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J. AM. CHEM. SOC. VOL. 126, NO. 40, 2004 12913

A R T I C L E S
Chow et al.
H), 7.10 (s, 6 H), 6.91 (s, 8 H), 6.86 (s, 4 H), 3.87 (s, 3 H), 3.59 (s, 4
H), 3.58 (s, 8 H), 3.55 (s, 12 H), 2.54 (t, J ) 7.2 Hz, 16 H), 1.67-1.48
(m, 16 H), 1.40-1.20 (m, 48 H), 0.87 (t, J ) 6.6 Hz, 24 H); 13C
NMR: 166.6, 143.0, 138.9, 138.8, 138.1, 137.5, 134.2, 130.5, 128.9,
128.5, 128.3, 127.3, 126.4, 52.1, 35.9, 35.8, 35.5, 35.1, 31.7, 31.5, 29.1,
22.6, 14.1; SEC retention time: 32.10 min; MS (MALDI-TOF, m/z):
1734.4 (M + Ag+). Anal. Calcd for C104H152O2S6: C, 76.79; H, 9.42.
Found: C, 77.04; H, 9.50.
56.8, 35.8, 31.7, 31.4, 29.1, 22.6, 14.1; SEC retention time: 32.70 min;
MS (MALDI-TOF, m/z): 1193.3 (M + Ag+). Anal. Calcd for
C66H102O6S3: C, 72.88; H, 10.14. Found: C, 73.01; H, 9.41.
[G2]-Nona(sulfone) (7). Starting from [G2]-nona(sulfide) 9 (1.00
g, 0.43 mmol), the crude product was purified by dissolving in CH2-
Cl2 and precipitated by the addition of MeOH to afford the title
compound 7 (0.72 g, 64%) as a white solid; mp 181-183 °C; 1H
NMR: 7.83 (s, 6 H), 7.81 (s, 3 H), 7.35 (s, 3 H), 7.07 (s, 12 H), 7.04
(s, 6 H), 4.31 (s, 12 H), 4.28 (s, 6 H), 4.19 (s, 18 H), 2.59 (t, J ) 7.7
Hz, 24 H), 1.68-1.48 (m, 24 H), 1.40-1.20 (m, 72 H), 0.87 (t, J )
6.7 Hz, 36 H); 13C NMR (CDCl3): 143.9, 134.7, 134.5, 130.1, 129.5,
129.3, 128.5, 128.1, 127.2, 60.1, 56.9, 56.3, 55.6, 35.7, 31.7, 31.4, 29.0,
22.6, 14.1; SEC retention time: 31.09 min; MS (MALDI-TOF, m/z):
2710.4 (M + Ag+). Anal. Calcd for C150H222O18S9: C, 69.24; H, 8.60.
Found: C, 68.97; H, 8.71.
General Procedure for the Synthesis of [Gn]-Oligo(sulfide)
Dendrimers (n ) 1-3). Powdered sodium methoxide (1.1 mol. equiv)
was added in one portion to a stirred solution of the thiolacetate [Gn]-
CH2SAc (1.0 mol. equiv) in THF/CH3OH (1/1) at 25 °C. After 5 min,
a solution of 1,3,5-tris(bromomethyl)benzene 13 (0.3 mol. equiv) in
dry THF was added and the mixture was stirred at 25 °C for 1 h. The
mixture was concentrated under reduced pressure and the residue was
diluted with water and extracted with EtOAc. The combined extracts
were dried (MgSO4), filtered and the solvent was removed under
reduced pressure. The crude product was purified by silica gel
chromatography (hexane/EtOAc ) 20/1) to give the target compound.
[G1]-Tri(sulfide) (8). Starting from [G1]-CH2SAc 12 (2.00 g, 6.0
mmol), [G1]-tri(sulfide) 8 (1.48 g, 83%) was isolated as a colorless
oil; Rf 0.76 (hexane/EtOAc ) 15/1); 1H NMR: 7.13 (s, 3 H), 6.93 (s,
6 H), 6.88 (s, 3 H), 3.59 (s, 6 H), 3.57 (s, 6 H), 2.58 (t, J ) 7.8 Hz, 12
H), 1.70-1.50 (m, 12 H), 1.40-1.25 (m, 36 H), 0.91 (t, J ) 6.6 Hz,
18 H); 13C NMR: 143.0, 138.7, 137.5, 128.3, 127.3, 126.4, 35.9, 35.7,
35.5, 31.7, 31.5, 29.1, 22.6, 14.1; SEC retention time: 33.05 min; MS
(MALDI-TOF, m/z): 1097.5 (M + Ag+). Anal. Calcd for C66H102S3:
C, 79.94; H, 10.37. Found: C, 79.66; H, 10.14.
[G3]-Heneicos(sulfone) (10). Starting from [G3]-heneicos(sulfide)
11 (120 mg, 0.02 mmol), the crude product was purified by dissolving
in CH2Cl2 and precipitated by addition of MeOH to give the title
1
compound 10 (70 mg, 51%) as a white solid; mp 188-190 °C; H
NMR: 7.86 (s, 3 H), 7.71 (s, 6 H), 7.69 (s, 12 H), 7.32 (s, 9 H), 7.04
(s, 24 H), 7.01 (s, 12 H), 4.42 (s, 6 H), 4.37 (s, 6 H), 4.23 (s, 24 H),
4.19 (s, 24 H), 4.16 (s, 24 H), 2.56 (t, J ) 7.8, 48 H), 1.68-1.48 (m,
48 H), 1.40-1.20 (m, 144 H), 0.86 (t, J ) 6.7 Hz, 72 H); 13C NMR:
143.84, 143.77, 143.7, 134.5, 134.3, 129.9, 129.7, 129.6, 129.4, 129.3,
128.8, 128.2, 127.1, 59.6, 56.9, 56.6, 56.2, 35.7, 31.9, 31.7, 31.4, 29.7,
29.3, 29.2, 29.0, 22.6, 14.1; SEC retention time: 29.57 min;
MS (MALDI-TOF, m/z): 5738.7 (M + Ag+). Anal. Calcd for
C318H462O42S21: C, 67.84; H, 8.27; Found: C, 67.48; H, 8.37.
[G2]-Nona(sulfide) (9). Starting from [G2]-CH2SAc 21 (1.50 g, 1.94
mmol), [G2]-nona(sulfide) 9 (1.05 g, 78%) was obtained as a colorless
oil; Rf 0.69 (hexane/EtOAc ) 15/1); 1H NMR: 7.17 (s, 9 H), 7.11 (s,
3 H), 6.95 (s, 12 H), 6.90 (s, 6 H), 3.60 (s, 18 H), 3.58 (s, 18 H), 2.57
(t, J ) 7.8 Hz, 24 H), 1.70-1.52 (m, 24 H), 1.42-1.23 (m, 72 H),
0.90 (t, J ) 6.6 Hz, 36 H); 13C NMR: 143.0, 138.7, 138.5, 138.4,
137.5, 128.5, 128.4, 128.3, 127.3, 126.4, 35.9, 35.54, 35.46, 31.7, 31.5,
29.1, 22.6, 14.1; SEC retention time: 31.03 min; MS (MALDI-TOF,
m/z): 2421.3 (M + Ag+). Anal. Calcd for C150H222S9: C, 77.86; H,
9.67. Found: C, 77.60; H, 9.51.
[G3]-Heneicos(sulfide) (11). Starting from [G3]-CH2SAc 24 (0.20
g, 0.12 mmol), [G3]-heneicos(sulfide) 11 (0.12 g, 66%) was obtained
as a colorless oil; Rf 0.67 (hexane/EtOAc ) 15/1); 1H NMR: 7.16 (s,
9 H), 7.13 (s, 12 H), 7.12 (s, 3 H), 7.07 (s, 6 H), 6.91 (s, 24 H), 6.86
(s, 12 H), 3.58 (s, 12 H), 3.56 (s, 48 H), 3.54 (s, 24 H), 2.53 (t, J ) 7.7
Hz, 48 H), 1.70-1.50 (m, 48 H), 1.40-1.20 (m, 144 H), 0.87 (t, J )
6.6 Hz, 72 H); 13C NMR: 143.0, 138.7, 138.63, 138.60, 138.53, 138.47,
137.5, 128.6, 128.5, 128.3, 127.3, 126.4, 35.9, 35.7, 35.6, 31.7, 31.5,
29.1, 22.6, 14.1; SEC retention time: 29.52 min; MS (MALDI-TOF,
m/z): 5064.4 (M + Ag+). Anal. Calcd for C318H462S21: C, 77.03; H,
9.39. Found: C, 77.04; H, 9.58
General Procedure for the Synthesis of [Gn]-Oligo(sulfone)
Dendrimers from [Gn]-Oligo(sulfide) Dendrimers (n ) 1-3). A
mixture of the [Gn]-oligo(sulfide) dendrimer and 35% hydrogen
peroxide (10 mol. equiv per sulfide) in CH2Cl2/HOAc (10/1) was
refluxed for 6 h. The solvent was removed under reduced pressure and
the residue was precipitated with ice water. The solid was collected,
redissolved in CH2Cl2 and washed with saturated NaHCO3 solution.
The organic solvents were dried (MgSO4), filtered, and concentrated
under reduced pressure. The crude product was purified as described
in the following text.
[G1]-Tri(sulfone) (6). Starting from [G1]-tri(sulfide) 8 (1.30 g, 1.3
mmol) and after purification of the crude product by silica gel
chromatography (CH2Cl2/EtOAc ) 30/1), [G1]-tri(sulfone) 6 (1.35 g,
95%) was obtained as a white solid; mp 103-105 °C; 1H NMR: 7.38
(s, 3 H), 7.04 (s, 9 H), 4.16 (s, 6 H), 4.08 (s, 6 H), 2.59 (t, J ) 7.7 Hz,
12 H), 1.70-1.50 (m, 12 H), 1.40-1.22 (m, 36 H), 0.88 (t, J ) 6.6
Hz, 18 H); 13C NMR: 143.9, 134.1, 129.5, 128.7, 128.1, 127.0, 59.2,
General Procedure for the Synthesis of [Gn]-Oligo(phenylene-
vinylene) Dendrimers by the Ramberg-Ba1cklund Rearrangement
of [Gn]-Oligo(sulfone) Dendrimers (n ) 1 and 2). Finely divided
KOH/Al2O3 was added to a rapidly stirred solution of the [Gn]-oligo-
(sulfone) dendrimer in THF/t-BuOH/CBr2F2 (1/1/1) at -45 °C. After
10 min, the mixture was filtered through a pad of Celite and washed
with CH2Cl2. The filtrate was evaporated under reduced pressure to
give the crude product that was further purified by silica gel chroma-
tography (hexane/CH2Cl2 ) 50/1).
[G1]-Tri(phenylenevinylene) Dendrimer (4). Starting from [G1]-
tri(sulfone) 6 (1.20 g, 1.1 mmol), the desired [G1]-tri(phenylene-
vinylene) dendrimer 4 was obtained (0.89 g, 91%) as a white solid:
1
mp 61-63 °C; Rf 0.77 (hexane/CH2Cl2 ) 8/1); H NMR: 7.57 (s, 3
H), 7.22 (s, 6 H), 7.20 (d, J ) 16.5 Hz, 3 H), 7.16 (d, J ) 16.5 Hz, 3
H), 6.95 (s, 3 H), 2.64 (t, J ) 7.8 Hz, 12 H), 1.75-1.60 (m, 12 H),
1.47-1.30 (m, 36 H), 0.92 (t, J ) 6.6 Hz, 18 H); 13C NMR: 143.2,
138.2, 137.0, 129.6, 128.3, 127.9, 124.1, 123.7, 36.0, 31.8, 31.5, 29.1,
22.6, 14.1; UV (λmax, log ꢀ): 320 nm (5.6); SEC retention time: 32.69
min; MS (MALDI-TOF, m/z): 889.2 (M + H+). Anal. Calcd for
C66H96: C, 89.12; H, 10.88. Found: C, 89.06; H, 10.79.
[G2]-Nona(phenylenevinylene) Dendrimer (5). Starting from [G2]-
nona(sulfone) 7 (0.70 g, 0.27 mmol), a mixture of (E)- and (Z)-
configurated [G2]-nona(phenylenevinylene) dendrimers (0.39 g, 72%)
was isolated as an oil. The all (E)-isomer 5 (0.26 g, 48%) could be
isolated as an oil by careful silica gel chromatography; Rf 0.30 (hexane/
1
CH2Cl2 ) 8/1); H NMR: 7.67 (s, 3 H), 7.62 (s, 9 H), 7.30 (s, 6 H),
7.22 (s, 12 H), 7.17 (d, J ) 16.5 Hz, 6 H), 7.18 (d, J ) 16.5 Hz, 6 H),
6.95 (s, 6 H), 2.63 (t, J ) 7.7 Hz, 24 H), 1.70-1.55 (m, 24 H), 1.47-
1.25 (m, 72 H), 0.90 (t, J ) 6.6 Hz, 36 H); 13C NMR: 143.3, 138.3,
138.1, 137.8, 137.0, 129.7, 129.2, 128.8, 128.4, 127.8, 124.1, 123.9,
36.0, 31.8, 31.5, 29.1, 22.6, 14.1; UV (λmax, log ꢀ): 322 nm (5.9); SEC
retention time: 30.63 min; MS (MALDI-TOF, m/z): 2007.1 (M+).
Anal. Calcd for C150H204: C, 89.76; H, 10.24. Found: C, 89.40; H,
10.19.
[G2]-Nona(phenyleneethylene) Dendrimer (25). A geometrical
mixture of the [G2]-nona(phenylenevinylene) dendrimer 5 (0.20 g, 0.10
mmol) in CH2Cl2/EtOH (v/v ) 1/1) and 10% Pd/C was stirred under
hydrogen at atmosphere pressure at 25 °C. After 48 h, the mixture was
9
12914 J. AM. CHEM. SOC. VOL. 126, NO. 40, 2004

Dendrimer Metamorphosis
A R T I C L E S
filtered through a pad of Celite and the filtrate was concentrated under
reduced pressure. The residue was chromatographed on silica gel
(hexane/CH2Cl2 ) 30/1) to give the target compound 30 (0.17 g, 82%)
strategies. We also show here that the [G1] and [G2]-oligo-
(sulfone)s could be transformed into the corresponding [G1]
and [G2]-oligo(phenylenevinylene)s. An unprecedented molec-
ular backbone transformation involving nine RB rearrangement
reactions on a [G2] dendritic species was realized and the
conversion efficiency of each RB rearrangement was 96%. Due
to steric shielding of the reaction sites and the heterogeneous
reaction conditions, such dendrimer metamorphosis failed to
realize in the case of the [G3]-heneicos(phenylenevinylene)
dendrimer. Nonetheless, we believe this dendrimer metamor-
phosis methodology could serve as an alternative dendrimer
synthesis strategy when both the dendrimer steric environment
and the reaction conditions are favorable.
1
as a colorless oil; Rf 0.42 (hexane/CH2Cl2 ) 8/1); H NMR: 7.00 (s,
3 H), 6.95 (s, 6 H), 6.93 (s, 3 H), 6.87 (s, 18 H), 2.90 (s, 12 H), 2.86
(s, 24 H), 2.56 (t, J ) 7.8 Hz, 24 H), 1.68-1.53 (m, 24 H), 1.40-1.20
(m, 72 H), 0.89 (t, J ) 6.8 Hz, 36 H); 13C NMR: 142.9, 142.3, 142.2,
142.1, 141.8, 126.2, 126.13, 126.08, 125.8, 38.33, 38.25, 36.0, 31.7,
31.6, 29.2, 22.6, 14.1; SEC retention time: 31.21 min; MS (MALDI-
TOF, m/z): 2134.4 (M + Ag+). Anal. Calcd for C150H222: C, 88.95;
H, 11.05. Found: C, 89.00; H, 10.78. The all (E)-[G2]-nona-
(phenylenevinylene) dendrimer 5 could also be similarly converted to
same compound 25 in 78% yield.
Conclusions
We report a new synthesis of oligo(sulfone) and oligo-
(phenylenevinylene) dendrimers by the combined use of den-
drimer interior functional group conversion and dendrimer
metamorphosis strategies. Hence, the [G1] to [G3]-oligo(sulfide)
dendrimers containing up to 21 sulfide moieties could be
converted into the corresponding [G1] to [G3]-oligo(sulfone)
dendrimers in good yields and purities. All the interior sulfide
functionalities could be transformed into the sulfone moieties
under homogeneous oxidative reaction conditions. The den-
drimer interior functionalization method is best suited for the
preparation of such oligo(dibenzyl sulfone) dendrimers as they
are not readily accessible by either the divergent or convergent
Acknowledgment. This paper is dedicated to Dr. Tze-Lock
Chan. We thank Prof. L. Li for mass spectral measurements,
the Physical Science Panel, CUHK (Account No. 2060145), and
an anonymous donor to the Chemistry Department for the
financial support.
Supporting Information Available: Selected 1H and 13C
NMR, mass spectra, and SEC chromatograms of all dendrons
and dendrimers. This material is available free of charge via
the Internet at http://pubs.acs.org.
JA046557M
9
J. AM. CHEM. SOC. VOL. 126, NO. 40, 2004 12915