Synthesis and chiroptical properties of amphiphilic dendrimers based on 2,3-dihydroxybenzyl alcohol

Article abstract of DOI:10.1016/S0040-4020(01)00957-7

The syntheses and chiroptical properties of amphiphilic dendrimers based on 2,3-dihydroxybenzyl alcohol up to the third generation are described. Water-solubility is imparted to the dendrimers using a selective palladium-catalyzed deprotection of allyl es

Full text of DOI:10.1016/S0040-4020(01)00957-7

TETRAHEDRON
Pergamon
Tetrahedron 57 A2001) 9393±9402
Synthesis and chiroptical properties of amphiphilic dendrimers
based on 2,3-dihydroxybenzyl alcohol
p
Â
Jacob G. Weintraub, Sevrine Broxer, Noel M. Paul and Jon R. Parquette
Department of Chemistry, The Ohio State University, Columbus, OH 43210, USA
This paper is dedicated to the memory of Willie W. Hsu
Received 19 September 2001; accepted 3 October 2001
AbstractÐThe syntheses and chiroptical properties of amphiphilic dendrimers based on 2,3-dihydroxybenzyl alcohol up to the third
generation are described. Water-solubility is imparted to the dendrimers using a selective palladium-catalyzed deprotection of allyl ester
terminal groups. Circular dichroism studies indicate that a transfer of chirality from the central core to the achiral branch segments does not
occur in any of the dendrimers in THF. However, a temperature-dependent Cotton effect associated with the 2,3-dialkoxybenzyl ether
branching subunit appears at the ®rst generation in water consistent with a transfer of chirality fromthe chiral core to the dendrons. This
effect disappears at the second and third generations suggesting greater conformational ¯exibility at higher dendrimer generation. The
increased ¯exibility at higher dendrimer generation is rationalized by a decrease in hydrophobic compression at higher dendrimer generation.
This work highlights the effect of asymmetric branching and solvent-induced compression in restricting the conformational mobility of
dendrimers. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
studies on chiral dendrimers have been conducted in good
solvents that induce a fully expanded conformation with
maximum ¯exibility.11 Recently, we observed that chiral,
amphiphilic dendrimers constructed with symmetrically
branched monomers based on 3,5-dihydroxybenzyl alcohol
experienced signi®cant aggregation in water that perturbed
the conformational equilibria of the dendrons and increased
the steric effect of the dendrons on the chiral central core.12
Chiral conformational order was not present in the dendrons
of these symmetrically branched systems. The purpose
of this work is to determine the effect of water13 on the
conformational properties of dendrimers constructed with
unsymmetrically branched dendrons based on 2,3-dihydroxy-
benzyl alcohol to restrict mobility and to create a potential
in a dendritic wedge to coil helically toward the focal point
upon compression in aqueous medium.14
Dendrimers are highly branched macromolecules that
are typically constructed using symmetrically branched
monomers to facilitate growth to high molecular weight
materials.1 Many of these systems maintain a relatively
¯exible structure that permits highly dynamic confor-
mational equilibria to exist in the branch segments.2 This
¯exibility severely impedes the ability to create higher
levels of conformational order in these molecules.3,4 For
example, attempts to induce stable chiral conformations in
dendrimers constructed with enantiomerically pure subunits
have been unsuccessful for many of the relatively ¯exible
systems that have been studied.5 Similarly, Meijer observed
that an enantiomerically pure dendrimer constructed using
three constitutionally different dendrons attached to a
central carbon atomexhibited no optical activity when
¯exible 3,5-branched polyarylether dendrons were
employed;6 however, restricting conformational mobility
by employing 2,6-branched polyarylether dendrons
permitted the expression of a small temperature-dependent
optical rotation.7 Theoretical8 and experimental9 studies
suggest that the molecular dimensions of dendrimers
expand in good solvents and collapse in poor solvents.
Therefore, conformational order should be maximal in
poor solvents such as water due to a hydrophobic effect
that compresses the dendrimer structure.10 Most chiroptical
2. Results and discussion
2.1. Dendron synthesis
Unsymmetrically branched polyarylether dendrons based on
2,3-dihydroxybenzyl alcohol were prepared in a convergent
manner from 2,3-dihydroxybenzaldehyde.14 Generational
growth was achieved by convergent O-alkylation of
2,3-dihydroxybenzaldehyde with the dendron mono-
bromides and focal point activation occurred by a subse-
quent reduction/bromination sequence AScheme 1). In
order to create a hydrophilic periphery, allyl ester groups
were chosen as terminal groups because of the potential to
Keywords: dendrimers; dihydroxybenzyl alcohol; chiroptical properties.
Corresponding author. Tel.: 11-614-292-5886; fax: 11-614-292-1685;
e-mail: parquett@chemistry.ohio-state.edu
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020A01)00957-7

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J. G. Weintraub et al. / Tetrahedron 57 *2001) 9393±9402
Table 1. GPC data Apolystyrene-equivalent molecular weights) of 2,3- and
3,5-branched dendrimers
3,5-Branched
MW Acalcd)
MW
Mn
AAllylO2C)8[G-1]±dendrimer
AAllylO2C)16[G-2]±dendrimer
AAllylO2C)32[G-3]±dendrimer
2526
4897
9638
2407
4951
9614
2095
4711
9264
2,3-Branched
AAllylO2C)8[G-1]±dendrimer
AAllylO2C)16[G-2]±dendrimer
AAllylO2C)32[G-3]±dendrimer
2526
4897
9638
2533
4149
6524
2522
4118
6467
the central core to the dendrons. Accordingly, 2,3-dihydroxy-
benzaldehyde was treated with methyl 4-bromomethyl-
benzoate in the presence of potassiumcarbonate and
18-C-6 in THF±DMF A4:1) at 708C affording 2a in 99%
yield AScheme 1). Initial attempts to install the allyl esters
by transesteri®cation of 2a with sodiumallyloxide in THF
afforded low yields of 2e contaminated by small amounts of
inseparable methyl esters. Extended reaction times led to
decomposition and decreased yields. Consequently, the
methyl esters of 2a were exhaustively hydrolyzed with
sodiumhydroxide in THF±H O at 658C affording diacid
2
2d in 92% yield. Subsequent deprotonation of 2d with
K2CO3 and alkylation with allyl bromide afforded 96%
yield of bis-allyl ester 2e without any contamination by
materials containing methyl esters. Subsequent reduction
of the focal aldehyde using NaBH4 in methanol was
unreliable due to the tendency of allyl esters to undergo
transesteri®cation in methanol. Similarly, the poor solubility
NaBH4 in THF caused reduction in this solvent to be
slow and dif®cult to reproduce. Reduction with diisobutyl-
aluminum hydride ADIBAL-H) in THF at 2788C produced
the focal alcohol A2f) in a reproducible 80% yield. Con-
version to the bromide was achieved at the ®rst generation
by exposure to phosphorous tribromide in CH2Cl2; however,
at later generations, this reagent caused cleavage of the
benzylic linkages.14 Therefore, at the second and third
generations, CBr4/PPh3 was used to install the focal bromide
without benzylic cleavage. Growth to the second and third
generation dendrons proceeded by iterative repetition of
these steps as shown in Scheme 1.
Scheme 1. Dendron synthesis. Aa) 1, K2CO3, 18-C-6, DMF±THF, 708C.
Ab) NaBH4, CH3OH, re¯ux. Ac) NaOH, THF±H2O. Ad) H2CvCHCH2Br,
K2CO3, 18-C-6, DMF±THF, 708C. Ae) Diisobutylaluminum hydride,
THF,2788C. Af) PBr3, CH2Cl2. Ag) CBr4, PPh3, THF.
liberate hydrophilic carboxylate groups upon palladium-
catalyzed deprotection.15 We have previously found this
deprotection method to be effective in exhaustively depro-
tecting the periphery of the 3,5-branched analogs of these
dendrimers because the solubility of partially hydrolyzed
intermediates is maintained throughout the course of the
hydrolysis.12 This method also permits the peripheral esters
to be deprotected under conditions that do not effect
hydrolysis of ester linkages that will be employed to link
2.2. Dendrimer synthesis and deprotection
1,3,4,6-tetra-O-A4-hydroxybenzoyl)-2,5-anhydro-d-mannitol,
5,16 was used as a tetrafunctional central core wherein
convergent dendron attachment occurred by O-alkylation
of the phenolic hydroxyl groups of the central core unit
AScheme 2). Accordingly, tetra-alkylation of the central
core, 5, with the ®rst AallylO2C)2[G-1]±CH2Br, 2g), second
AallylO2C)4[G-2]±CH2Br, 3c) and third AallylO2C)8[G-3]±
CH2Br, 4c) generation dendron monobromides was accom-
plished using K2CO3/18-C-6 in THF±DMF A4:1) at 708C.
Puri®cation over silica gel afforded monodisperse dendri-
mers with molecular weights of 2526 A6a, 79%), 4897 A7a,
46%) and 9638 A8a, 51%) with 8, 16 and 32 terminal allyl
esters, respectively. GPC analysis indicated that the dendri-
mers were monodisperse; however, the polystyrene-equiva-
lent molecular weights were signi®cantly lower than the
theoretical molecular weights of these dendrimers and
the polystyrene-equivalent weights of the analogous
3,5-branched dendrimers12 ATable 1). The signi®cantly
Scheme 2. Dendrimer synthesis.

J. G. Weintraub et al. / Tetrahedron 57 *2001) 9393±9402
9395
Figure 1. Unsymmetrically branched amphiphilic dendrimers. Aa) 2.5 mol% Pd2Adba)3CHCl3±25 mol% PPh3, 1.2 M HCO2H/AC4H9)3N A1:1) in THF, 508C.
lower molecular weights observed for the isomeric 2,3-
branched dendrimers relative to the 3,5-branched archi-
tecture is consistent with a more compact dendrimer con-
formation. MALDI-TOF mass spectrometry revealed
molecular ions consistent with the expected molecular
weights. Deprotection of the allyl esters of 6a±8a was
effected by exposure to 2.5 mol% Pd2Adba)3CHCl3±
25 mol% PPh3 and excess HCO2H/AC4H9)3N A1:1) in THF
at 508C for 12 h AFig. 1). This process exhaustively depro-
tected the dendrimer periphery affording amphiphilic
dendrimers 6b±8b in high yields. Negative ion electrospray
mass spectrometry displayed ions at AM21H)/eˆ2229 for
6b and AM23H)/3eˆ1417 for 7b; however, we have been
unable to observe distinct ions with dendrimer 8b.

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J. G. Weintraub et al. / Tetrahedron 57 *2001) 9393±9402
Figure 2. CD spectra of central core 5 and allyl ester terminated dendrimers
6a±8a in THF at 258C.
Figure 4. CD spectra of central core 5 and carboxylic acid terminated
dendrimers 6b±8b in water ApH 9, phosphate).
2.3. Circular dichroism studies
Circular dichroic spectra were recorded for 5 and den-
drimers 6±8 to determine the effect of the chiral core on
the conformational equilibria of the achiral dendrons as a
function of dendrimer generation and solvent quality. In
THF, the chiral central core, 5, and the allyl ester terminated
dendrimers, 6a±8a, exhibited very weak excitonic couplets
associated with a transition at 262 nmof the 4-alkoxy-
benzoate linker present at the central core AFig. 2). A
similarly weak couplet was observed in the CD spectra of
the carboxylate-terminated dendrimers, 6b±8b, in THF
AFig. 3). The CD spectra depicted in Figs. 2 and 3 were
not sensitive to temperature. Consequently, the achiral
dendrons were not contributing to the observed chiroptical
properties suggesting a lack of chiral conformational order
in the branch segments of dendrimers 6a/b±8a/b in organic
solvents.
Figure 5. CD spectrumof 6b in water ApH 9, phosphate) as a function of
temperature.
272 nmwas observed for the ®rst generation dendrimer,
6b, in water that was absent in THF. Further, decreasing
the temperature to 218C doubled the intensity of the CE
while increasing the temperature to 658C signi®cantly
reduced the intensity of the CE AFig. 5). This temperature
dependence is consistent with a conformational origin of the
peak.
The CD spectra of 5 and 6b±8b were recorded in water ApH
9.0, phosphate) in order to determine whether hydrophobic
compression of these unsymmetrically branched dendrimers
would facilitate the transfer of chirality fromthe central core
to the achiral dendrons more effectively than observed for
analogous 3,5-branched polyarylether dendrimers. In the
3,5-branched systems, the intensity of all the CD spectra
were signi®cantly reduced in water relative to THF due to
a putative collapse of the dendrimer structure in water;
however, no conformational order in the dendritic branches
was apparent by CD spectroscopy.17 Interestingly, in
aqueous medium, 5 and 7b±8b exhibited ¯at lines in the
CD spectra similar to the spectra of the 3,5-branched
systems AFig. 4).12 An intense Cotton effect ACE) at ca.
Inspection of the ultraviolet spectrumshown in Fig. 6
suggests that this CE arises froma transition of the
2,3-dialkoxybenzyl ether chromophore present in the
branch segments of the dendrimer. Dendrimer 6b displayed
a UV spectrumin water ApH 9, phosphate) having two
overlapping transitions at approximately 262 and 275 nm.
Comparison of the spectra of dendrimer 6b, central core 5
and AHO2C)2[G-1]±CH2OH A2c)18 indicate that the peak
at 262 nmis due to a transition of the 4-alkoxybenzoate
linkage because, although present in 6b and 5, this transition
is not present in the spectrumof 2c. The peak at approxi-
mately 275 nm is responsible for the CE observed in the CD
spectrumof dendrimer 6b in water. Comparison of UV
Figure 3. CD spectra of carboxylic acid terminated dendrimers 6b±8b in
THF.
Figure 6. UV spectra of 2,3-dimethoxybenzyl alcohol, 2c and 6b in H2O
ApH 9, phosphate) and central core 5 in THF.

J. G. Weintraub et al. / Tetrahedron 57 *2001) 9393±9402
9397
spectra of dendrimer 6b and dendron 2c indicates that the
4. Experimental
2,3-dialkoxybenzyl ether linkage in the dendritic wedge of
the dendrimer gives rise to this transition and is responsible
for the CE observed in the CD spectrum. The UV spectrum
of 2,3-dimethoxybenzyl alcohol, measured in water,
also exhibited a transition at 275 nmconsistent with this
assignment.
4.1. General
Melting points were determined in open capillaries and are
uncorrected. H NMR spectra were recorded at 250, 400,
1
500 or 600 MHz and 13C NMR spectra at 100 or 125 MHz.
EI or FAB mass spectra were recorded at The Ohio State
University Chemical Instrument Center. MALDI-TOF
spectrometry was performed using 2,5-dihydroxybenzoic
acid or 3-indoleacrylic acid as the matrix in tetrahydrofuran
ATHF). Circular dichroism ACD) measurements were carried
out on an Aviv 202 CD spectrometer, using optical grade
solvents and quartz glass cuvettes with a 10 mm path length.
All reactions were performed under an argon or nitrogen
atmosphere. Dimethylformamide ADMF) was dried by
distillation frombariumoxide or magnesiumsulfate;
Therefore, we can conclude that a conformational change
occurs in water that induces a circular dichroismin the
2,3-dialkoxybenzyl subunit present in the dendritic wedges
of 6b. This CE indicates that the chirality of the central core
was transferred to the achiral branch segments of the den-
drimer in aqueous media. The induction of chirality into the
dendrons disappears at the second A7b) and third A8b)
generations and for all the dendrimers in a nonaqueous
solvent. The absence of induced chirality in the dendritic
wedges at higher dendrimer generation suggests that greater
conformational freedom exists in these systems. We
have previously observed that analogous 3,5-branched
dendrimers in aqueous medium experience a generation-
dependent aggregation that decreased with increasing
dendrimer generation as evidenced by multi-angle laser
light scattering studies AMALLS). This aggregation
behavior could be rationalized by increased water com-
patibility, indicated by MALLS, that is induced by the
development of a more globular morphology at higher
generations.12 Consequently, the increased conformational
mobility at higher dendrimer generations can be rationalized
by the decreasing hydrophobic compression that occurs as
the dendrimers become more compatible with the aqueous
phase at higher dendrimer generation. These observations
highlight the importance of an unsymmetrically branched
repeat unit and solvent-induced compression in restricting
the conformational mobility in dendrimers.
THF was distilled fromsodium/benzophenone ketyl and
dichloromethane was distilled from calcium hydride.
Chromatographic separations were performed on silica gel
Ê
60 A230±400 mesh, 60 A) using the indicated solvents.
4.1.1. +CH3O2C)2[G-1]±CHO +2a). Methyl 4-bromo-
methylbenzoate A17.41 g, 76.0 mmol), 2,3-dihydroxybenz-
aldehyde A5.00 g, 36.2 mmol), potassium carbonate
A25.02 g, 181.0 mmol) and 18-C-6 A1.90 g, 7.2 mmol)
were sequentially dissolved in a dry 4:1 THF/DMF
A181.0 mL). After heating the reaction mixture at 708C for
10 min, the solvent was removed over 20±30 min under
vacuum A60 mmHg). If necessary, this process was repeated
by adding an aliquot of solvent followed by removal, until
the reaction was complete by TLC. The resultant residue
was then partitioned between water A200 mL) and CH2Cl2
A200 mL) and the organic layer was washed with water
A2£100 mL) and saturated NaCl A2£100 mL) then dried
over MgSO4. Concentration of the CH2Cl2 layer afforded
2a as an off-white powder A15.5 g, 35.7 mmol, 99%).
1
3. Conclusion
Mpˆ125±1268C. H NMR A300 MHz, CDCl3) d 3.91 As,
3H), 3.92 As, 3H), 5.20 As, 2H), 5.24 As, 2H), 7.12 At,
Jˆ7.92 Hz, 1H), 7.21 Add, Jˆ8.07, 1.59 Hz, 1H), 7.39 Ad,
Jˆ8.46 Hz, 2H), 7.41 Aobscured d, 1H), 7.48 Ad, Jˆ8.16 Hz,
2H), 7.99 Ad, Jˆ8.22 Hz, 2H), 8.04 Ad, Jˆ8.25 Hz, 2H),
10.31 As, 1H). 13C NMR Appm) A75 MHz, CDCl3) 52.0,
52.1, 70.6, 75.6, 119.9, 120.2, 124.4, 127.0, 127.8, 129.7,
129.9, 130.0, 130.5, 141.1, 141.3, 151.0, 151.5, 166.5,
189.6. Anal. calcd for C25H22O7: C, 69.12; H, 5.10.
Found: C, 69.09; H, 5.10.
A convenient synthesis of chiral, amphiphilic dendrimers up
to the third generation based on an unsymmetrically
branched subunit, 2,3-dihydroxybenzyl alcohol, has been
described. GPC analysis indicates that these materials are
much more compact than the analogous 3,5-branched
dendrimers as a consequence of the 2,3-branching pattern.
Although these dendrimers are highly ¯exible, this work
underscores the importance of the hydrophobic effect
in increasing structural rigidity. At the ®rst dendrimer
generation in water, the chirality of the central core is trans-
ferred to the 2,3-dihydroxybenzyl linkage of the dendron as
indicated by the appearance of a CE upon dissolving in
water. Since we have not previously observed this effect
for the analogous 3,5-branched systems, the unsymmetric
branching appears to be requisite in creating this local
chirality in the dendron. The chirality is localized to this
chromophore and does not extend further into the dendrons
at higher generations presumably due to a decreasing hydro-
phobic effect at higher dendrimer generation. Therefore, we
can conclude that unsymmetrical dendron branching and
hydrophobic collapse in water contributes to chirality
transfer, but to achieve more extensive conformational
order will require signi®cantly more rigid dendrimer
scaffolds in conjunction with these effects.
4.1.2. +CH3O2C)2[G-1]±CH2OH +2b). A suspension of
ACH3O2C)2[G-1]±CHO, 2a, A11.75 g, 27.0 mmol) in metha-
nol A135.0 mL) was stirred at re¯ux under nitrogen for
10 min, whereupon the addition of sodium borohydride
A1.12 g, 29.7 mmol) resulted in a homogeneous mixture.
After 3 h, the mixture was allowed to cool to room tempera-
ture and 0.1 M NaOH A150 mL) was added. This mixture
was stirred for 5 min and then partitioned between CH2Cl2
A150 mL) and water A150 mL). The aqueous layer was
extracted with CH2Cl2 A2£100 mL) and the combined
organic layers were dried over MgSO4. Concentration of
the CH2Cl2 layer afforded 2b as a tan solid A11.32 g,
25.93 mmol, 96%). Mpˆ88±908C. 1H NMR A300 MHz,
CDCl3) d 3.88 As, 3H), 3.90 As, 3H), 4.63 As, 2H), 5.12
As, 2H), 5.13 As, 2H), 6.91 Add, Jˆ7.50, 2.08 Hz, 1H),

9398
J. G. Weintraub et al. / Tetrahedron 57 *2001) 9393±9402
6.92±7.07 Am, 2H), 7.44 Ad, Jˆ8.06 Hz, 2H), 7.45 Ad, Jˆ
7.94 Hz, 2H), 7.97 Ad, Jˆ8.34 Hz, 2H), 8.00 Ad, Jˆ8.38 Hz,
2H). 13C NMR Appm) A75 MHz, CDCl3) 52.0, 52.0, 61.0,
70.3, 74.4, 113.9, 121.4, 124.4, 126.9, 127.6, 129.6, 129.8,
135.2, 141.8, 142.5, 145.9, 151.2, 166.5, 166.6. Anal. calcd
for C25H24O7: C, 68.80; H, 5.54. Found: C, 68.68; H, 5.50.
A0!5% CH2Cl2/diethyl ether) affording a white solid
A2.89 g, 5.95 mmol, 96%). Mpˆ69±728C ACH2Cl2/diethyl
1
ether). H NMR A400 MHz, CDCl3) d 4.83 Am, 4H), 5.22
As, 2H), 5.26 As, 2H), 5.29 Adt, Jˆ9.44, 1.0 Hz, 1H), 5.42 Adt,
Jˆ17.2, 1.3 Hz, 1H), 6.03 Am, 2H), 7.14 At, Jˆ8.0 Hz, 1H),
7.21 Ad, Jˆ8.0 Hz, 1H), 7.43 Am, 3H), 7.51 Ad, Jˆ8.2 Hz,
2H), 8.03 Ad, Jˆ8.2 Hz, 2H), 8.08 Ad, Jˆ8.2 Hz, 2H), 10.31
As, 1H). 13C NMR Appm) A100 MHz, CDCl3) 66.1, 66.2,
71.1, 76.1, 118.7, 118.8, 120.4, 120.7, 124.9, 127.5, 128.4,
130.4, 130.5, 130.6, 130.8, 132.6, 132.6, 141.7, 141.9,
151.7, 152.2, 166.2, 166.2, 190.1. IR Aneat ®lm): 1726,
1678 cm21. MS for C29H26O7Na AElectrospray) AM1Na)
calcd 509.2; obsd 509.2. Anal. calcd for C29H26O7: C,
71.59; H, 5.39. Found: C, 71.36, H, 5.46.
4.1.3. +HO2C)2[G-1]±CH2OH +2c). ACH3O2C)2[G-1]±
CH2OH A2b) A14.59 g, 33.4 mmol) was dissolved in THF
A100 mL) to which NaOH A3.42 g, 85.5 mmol) in water
A100 mL) was added. The reaction was heated at re¯ux for
14 h. The reaction was cooled to ambient temperature,
diluted with water A75 mL), and acidi®ed to pH 1 with
HCl 1.2N. The resulting milky solution was cooled to
248C for 3 h and a white solid was isolated by ®ltration.
The solid was dried over phosphorous pentoxide under
vacuumA0.3 mmHg) for several days to afford a white
solid A13.01 g, 31.8 mmol, 96%). Mpˆ218±2258C
4.1.6. +AllylO2C)2[G-1]±CH2OH +2f). AAllylO2C)2[G-1]±
CHO A2e) A2.77 g, 5.70 mmol) was dissolved in dry THF
A15 mL) and cooled to 2788C, whereupon diisobutylalu-
minum hydride ADIBAL-H) A7.9 mL, 7.9 mmol, 1 M in
hexanes) was added dropwise via syringe. After 10 min,
aqueous saturated ammonium chloride A20 mL) was care-
fully added and the mixture was warmed up to ambient
temperature. The mixture was then partitioned between
saturated aqueous sodiumbicarbonate A14Lm) and
CH2Cl2 A46 mL). The organic layer was extracted further
with CH2Cl2 A4£50 mL) and the combined organic layers
were washed with brine A75 mL), dried AMgSO4), and the
solvent was removed in vacuo. Puri®cation by ¯ash
chromatography ASiO2) A95:5 CH2Cl2/diethyl ether)
afforded 2f as a white solid A2.22 g, 4.55 mmol, 80%).
Mpˆ63±668C ACH2Cl2/diethyl ether). 1H NMR A400
MHz, CDCl3) d 4.63 As, 2H), 4.83 Abs, 4H), 5.17 As, 2H),
5.19 As, 2H), 5.29 Ad, Jˆ10.4 Hz, 2H), 5.42 Ad, Jˆ17.1 Hz,
2H), 6.05 Am, 2H), 6.98 At, Jˆ7.7 Hz, 2H), 7.05 Ad, Jˆ
7.8 Hz, 1H), 7.46±7.51 Am, 4H), 8.03±8.08 Am, 4H). 13C
NMR Appm) A100 MHz, CDCl3) 60.6, 64.7, 64.8, 69.5,
73.6, 113.2, 117.4, 117.5, 120.7, 123.6, 126.1, 126.9,
129.0, 129.1, 131.3, 131.3, 134.3, 141.0, 141.7, 145.1,
1
Awater). H NMR A400 MHz, DMSO-d6) d 4.52 As, 2H),
5.10 As, 2H), 5.25 As, 2H), 7.03±7.11 Am, 3H), 7.54 Ad, Jˆ
8.2 Hz, 2H), 7.58 Ad, Jˆ8.2 Hz, 2H), 7.93 Ad, Jˆ7.9 Hz,
2H), 7.97 Ad, Jˆ9.4 Hz, 2H), 12.95 Abs, 2H). 13C NMR
Appm) A400 MHz, DMSO-d6) 58.4, 69.7, 73.9, 113.2,
120.6, 124.4, 127.7, 128.2, 129.6, 129.8, 130.5, 130.5,
136.8, 142.5, 143.0, 144.9, 151.2, 167.4, 167.5. IR A®lm):
3407, 1692 cm21 MS for C23H20O7Na AM1Na) AQ-TOF
Electrospray MS) calcd 431.1107; obsd 431.1111.
4.1.4. +HO2C)2[G-1]±CHO +2d). ACH3O2C)2[G-1]±CHO
A2a) A9.28 g, 21 mmol) was suspended in THF A35 mL) and
2 M NaOH Aaq.) A25 mL). THF A50 mL) and water A50 mL)
were added to dissolve the solid and the resulting homo-
geneous solution was heated at re¯ux for 5 h. The reaction
mixture was cooled to ambient temperature, diluted with
water A50 mL), and acidi®ed to pH 1 with 1.2N HCl Aaq.).
The solid was isolated by ®ltration and the resulting ®ltrate
was rinsed with cold water, cold diethyl ether, and dried
over phosphorous pentoxide under vacuumA0.3 mmHg)
affording 2d as a white solid A7.81 g, 19 mmol, 92%).
Mpˆ257±2628C Adec.) AH2O). 1H NMR A400 MHz,
DMSO-d6) d 5.26 As, 2H), 5.33 As, 2H), 7.22 At, Jˆ7.8 Hz,
1H), 7.29 Ad, Jˆ7.4 Hz, 1H), 7.51 Ad, Jˆ7.8 Hz, 3H), 7.61
Ad, Jˆ7.8 Hz, 2H), 7.90 Ad, Jˆ7.8 Hz, 2H), 7.97 Ad, Jˆ
7.8 Hz, 2H), 10.19 As, 1H), 13.00 Abs, 2H). 13C NMR
Appm) A100 MHz, DMSO-d6) 70.1, 75.3, 119.4, 120.6,
125.1, 127.9, 128.8, 129.7, 129.9, 130.2, 130.8, 130.9,
141.7, 141.8, 150.8, 152.1, 167.4, 190.1. IR A®lm): 3416,
1683 cm21. MS for C23H18O7Na AM1Na) AQ-TOF Electro-
spray MS) calcd 429.09; obsd 429.1. Anal. calcd for
C23H18O7: C, 67.98; H, 4.46. Found: C, 67.89; H, 4.62.
150.4, 165.0, 165.1. IR Adry ®lm): 3340, 1714 cm21
.
HRMS AEI) for C29H28O7 calcd 488.1835; obsd 488.1841.
Anal. calcd for C29H28O7: C, 71.30; H, 5.78; Found: C,
71.54, H, 5.61.
4.1.7. +AllylO2C)2[G-1]±CH2Br +2g). AAllylO2C)2[G-1]±
CH2OH A2f) A2.34 g, 4.79 mmol) was dissolved in CH2Cl2
A4 mL) at 08C, and phosphorous tribromide A228 mL, 0.65 g,
2.39 mmol) was added. After 1.5 h, the solvent was evapo-
rated to dryness and the residue was partitioned between
CH2Cl2 A50 mL) and water A50 mL). The aqueous layer
was washed with CH2Cl2 A3£50 mL) and the combined
organic layers were dried AMgSO4), concentrated in vacuo
and puri®ed by ¯ash chromatography ASiO2) ACH2Cl2)
affording 2g as a white solid A2.40 g, 4.36 mmol, 91%).
4.1.5. +AllylO2C)2[G-1]±CHO +2e). AHO2C)2G-1-CHO
A2d) A2.53 g, 6.23 mmol), K2CO3 A3.44 g, 24.9 mmol), and
18-C-6 A0.17 g, 0.64 mmol) were dissolved in THF/DMF
4:1 A50 mL) and allyl bromide A1.5 mL, 2.1 g, 17 mmol)
was added. After heating the mixture at re¯ux for 18 h,
the mixture was cooled to ambient temperature, the solvent
removed in vacuo. The resulting residue was partitioned
between dichloromethane A150 mL) and water A100 mL)
and the aqueous phase was washed with dichloromethane
A3£100 mL). The combined organic layers were then dried
over MgSO4, ®ltered and the concentrated in vacuo to a
yellow solid. Puri®cation by ¯ash chromatography ASiO2)
1
Mpˆ69±778C ACH2Cl2). H NMR A400 MHz, CDCl3) d
4.53 As, 2H), 4.84 Abs 4H), 5.18 As, 2H), 5.26 As, 2H), 5.35
Ad, Jˆ10.4 Hz, 2H), 5.42 Ad, Jˆ16.4 Hz, 2H), 6.05 Am, 2H),
6.94 Add, Jˆ7.11, 2.5 Hz, 1H), 7.02 At, Jˆ7.10 Hz, 2H), 7.49
Ad, Jˆ8.1 Hz, 2H), 7.54 Ad, Jˆ8.1 Hz, 2H), 8.06 Ad,
Jˆ8.2 Hz, 2H), 8.10 Ad, Jˆ8.2 Hz, 2H). 13C NMR Appm)
A100 MHz, CDCl3) 66.0, 66.1, 70.8, 74.4, 115.2, 118.7,
118.8, 123.8, 125.0, 127.4, 128.1, 128.3, 130.1, 130.3,
130.3, 130.4, 132.6, 132.7, 132.9, 142.1, 143.1, 146.9,
152.1, 166.3, 166.5. IR Aneat ®lm): 1721 cm21. HRMS

J. G. Weintraub et al. / Tetrahedron 57 *2001) 9393±9402
9399
AEI) for C29H27BrO6 AM) calcd 550.0991; obsd 550.0993.
Anal. calcd for C29H27BrO6: C, 63.17; H, 4.94; Br, 14.49.
Found: C, 63.01; H, 4.92; Br, 14.36.
Mpˆ70±818C ACH2Cl2/diethyl ether). 1H NMR A400
MHz, CDCl3) d 4.45 As, 2H), 4.79±4.84 Am, 8H), 5.03 As,
2H), 5.07 As, 2H), 5.10 As, 2H), 5.15 As, 2H), 5.16 As, 2H),
5.22 As, 2H), 5.25±5.31 Am, 4H), 5.37±5.45 Am, 4H), 5.91±
6.10 Am, 4H), 6.82 Add, Jˆ2.9 Hz, 6.7 Hz, 1H), 6.87±7.04
Am, 7H), 7.17 Ad, Jˆ6.78 Hz, 1H), 7.38 Ad, Jˆ8.1 Hz, 2H),
7.40 Ad, Jˆ8.2 Hz, 2H), 7.45 Ad, Jˆ8.2 Hz, 2H), 7.49 Ad,
Jˆ8.2 Hz, 2H), 7.90 Ad, Jˆ8.2 Hz, 2H), 7.95 Ad, Jˆ8.2 Hz,
2H), 7.99 Ad, Jˆ8.4 Hz, 2H), 8.02 Ad, Jˆ8.4 Hz, 2H). 13C
NMR Appm) A100 MHz, CDCl3) 28.9, 53.9, 65.9, 66.0, 66.1,
66.1, 66.6, 70.3, 70.8, 74.9, 75.0, 114.7, 118.6, 118.6, 118.7,
118.7, 127.4, 127.4, 127.9, 128.2, 130.0, 130.2, 130.2,
130.3, 130.3, 130.4, 132.7, 132.7, 132.7, 132.7, 132.7,
142.4, 142.5, 143.1, 143.5, 146.6, 151.8, 152.3, 166.3,
166.3, 166.3, 166.4. IR Adry ®lm): 1720 cm21. MS for
C65H59BrO14K AM1K) AMALDI-TOF) calcd 1183.18;
obsd 1184.5. Anal. calcd for C65H59BrO14: C, 68.24; H,
5.20. Found: C, 68.00, H, 5.32.
4.1.8. +AllylO2C)4[G-2]±CHO +3a). AAllylO2C)2[G-1]±
CH2Br A2g) A3.65 g, 6.62 mmol), was converted to AAllyl
O2C)4-[G-2]±CHO A3a) using 2,3-dihydroxybenzaldehyde
A0.46 g, 3.35 mmol), K2CO3 A3.36 g, 24.3 mmol) and 18-
C-6 A0.11 g, 0.40 mmol) in THF A5 mL) and DMF
A1.5 mL) as described for 2a. Puri®cation by ¯ash chromato-
graphy ASiO2) A95:5 CH2Cl2/diethyl ether) afforded 3a as a
white solid A3.36 g, 3.12 mmol, 99%). Mpˆ100±1058C
ACH2Cl2/diethyl ether). 1H NMR A400 MHz, CDCl3) d
4.80±4.84 Am, 8H), 5.00 As, 2H), 5.04 As, 2H), 5.14 Abs,
4H), 5.19 Abs, 4H), 5.28 Am, 4H), 5.42 Am, 4H), 5.98±6.08
Am, 4H), 6.95±7.06 Am, 8H), 7.31±7.50 Am, 9H), 7.91±7.97
Am, 4H), 8.03±8.07 Am, 4H), 10.18 As, 1H). 13C NMR Appm)
A100 MHz, CDCl3) 65.4, 65.4, 66.2, 70.2, 70.3, 71.2, 74.2,
74.4, 114.2, 118.0, 118.1, 118.2, 119.5, 121.5, 124.0, 124.2,
124.4, 126.8, 127.2, 127.6, 129.5, 129.6, 129.8, 129.8,
130.3, 130.8, 132.0, 141.7, 142.4, 142.5, 151.2, 165.7,
4.1.11. +AllylO2C)8[G-3]±CHO +4a). AAllylO2C)4[G-2-]
CH2Br A3c) A0.90 g, 0.79 mmol), was converted to Aallyl
O2C)8[G-3]±CHO A4a) using 2,3-dihydroxybenzaldehyde
A0.056 g, 0.4 mmol), K2CO3 A0.48 g, 3.5 mmol) and 18-C-
6 A11 mg, 0.04 mmol) in THF A4 mL) and DMF A1 mL) as
described for 2a. Puri®cation by ¯ash chromatography
ASiO2) A95:5 CH2Cl2/diethyl ether) affording 4a as a white
solid A0.69 g, 0.3 mmol, 78%). Mpˆ105±1108C ACH2Cl2/
190.2. IR Aneat ®lm): 1720, 1687 cm21
. MS for
C65H58O15K AMALDI-TOF) AM1K) calcd 1117.4; obsd
1117.3. Anal. calcd for C65H58O15: C, 72.34; H, 5.42;
Found: C, 72.44, H, 5.42.
4.1.9. +AllylO2C)4[G-2]±CH2OH +3b). AAllylO2C)4[G-2]±
CHO A3a) A3.36 g, 3.11 mmol) was converted to AAllyl
O2C)4[G-2]±CH2OH A3b) using DIBAL-H A4.5 mL,
4.5 mmol, 1 M in hexanes) in THF A11 mL) at 2788C for
2 h as described for 2f. Puri®cation by ¯ash chromatography
ASiO2) A95:5 CH2Cl2/diethyl ether) afforded 3b as a white
solid A2.51 g, 2.32 mmol, 75%). Mpˆ85±908C ACH2Cl2/
1
diethyl ether). H NMR A400 MHz, CDCl3) d 4.75 Abd,
2H), 4.77 Abd, 2H), 4.78±4.84 Am, 12H), 4.89 As, 2H),
4.95 As, 2H), 4.97 As, 2H), 5.03 As, 4H), 5.05 As, 2H), 5.06
As, 2H), 5.08 As, 2H), 5.09 As, 2H), 5.11 As, 4H), 5.14 As, 4H),
5.15 As, 2H), 5.24±5.31 Am, 8H), 5.38±5.43 Am, 8H), 5.95±
6.09 Am, 8H), 6.76±7.05 Am, 21H), 7.21±7.30 Am, 4H),
7.37±7.43 Am, 8H), 7.46±7.49 Am, 4H), 7.87±8.20 Am,
8H), 7.81±8.31 Am, 4H), 10.1 As, 1H). 13C NMR Appm)
A100 MHz, CDCl3) 65.9, 66.0, 66.0, 66.0, 66.5, 70.6, 70.7,
70.8, 71.9, 74.7, 74.8, 74.9, 114.5, 118.6, 118.7, 118.7,
118.7, 127.4, 127.4, 127.7, 127.7, 128.2, 130.0, 130.0,
130.2, 130.3, 130.3, 130.4, 132.7, 132.7, 132.7, 132.7,
142.3, 142.3, 143.1, 143.2, 146.2, 151.8, 151.8, 166.3,
1
diethyl ether). H NMR A400 MHz, CDCl3) d 1.89 Abs,
1H), 4.51 As, 2H), 4.79±4.84 Am, 8H), 5.04 Abd, 4H), 5.11
As, 2H), 5.12 As, 2H), 5.15 As, 2H), 5.17 As, 2H), 5.26±5.31
Am, 4H), 5.37±5.39 Am, 2H), 5.42±5.44 Am, 2H), 5.92±6.10
Am, 4H), 6.82±7.08 Am, 9H), 7.35 Ad, Jˆ8.2 Hz, 2H), 7.39
Ad, Jˆ8.2 Hz, 2H), 7.43 Ad, Jˆ8.2 Hz, 2H), 7.47 Ad, Jˆ
8.2 Hz, 2H), 7.92 Ad, Jˆ8.2 Hz, 2H), 7.95 Ad, Jˆ8.2 Hz,
2H), 8.02 Ad, Jˆ8.2 Hz, 2H), 8.05 Ad, Jˆ8.2 Hz, 2H). 13C
NMR Appm) A100 MHz, CDCl3) 62.0, 65.9, 66.0, 66.1, 66.5,
70.5, 70.8, 70.9, 74.9, 75.0, 114.3, 114.7, 115.0, 118.6,
118.6, 118.7, 118.7, 121.6, 123.4, 124.6, 124.8, 124.8,
127.4, 127.4, 128.2, 127.8, 127.9, 130.1, 130.1, 130.2,
130.3, 130.4, 130.4, 131.9 132.5, 132.6, 132.6, 132.7,
132.7, 135.6, 142.3, 142.3, 143.1, 143.2, 146.4, 151.8,
152.0, 166.3, 166.4. IR Aneat ®lm): 3329, 1721 cm21. MS
for C65H60O15Na AMALDI-TOF) AM1Na) calcd 1103.4;
obsd 1103.0. Anal. calcd for C65H60O15: C, 72.21; H, 5.59.
Found: C, 72.32, H, 5.49.
166.3, 190.9. IR Aneat ®lm): 1720 cm21
. MS for
C137H122O31Na AM1Na) AMALDI-TOF) calcd 2287.4;
obsd 2287.4. Anal. calcd for C137H122O31: C, 72.67; H,
5.43. Found: C, 72.49, H, 5.39.
4.1.12. +AllylO2C)8[G-3]±CH2OH +4b). AAllylO2C)8
[G-3]±CHO A4a) A0.68 g, 0.3 mmol) was converted to
AallylO2C)8[G-3]±CH2OH A4b) using DIBAL-H A0.4 mL,
0.4 mmol, 1 M in hexanes) in THF A2.8 mL) at 2788C for
30 min as described for 2f. Puri®cation by ¯ash chroma-
tography ASiO2) A0!5% diethyl ether/CH2Cl2) affording
4b a white glass A0.41 g, 0.18 mmol, 59%). 1H NMR
A400 MHz, CDCl3) d 4.46 As, 2H), 4.77±4.83 Am, 16H),
4.91 As, 2H), 4.96 As, 2H), 4.98 As, 2H), 5.04 As, 2H), 5.07
Am, 20H), 5.21±5.29 Am, 8H), 5.31±548 Am, 8H), 5.96±6.10
Am, 8H), 6.70 Am, 1H), 6.82±7.15 Am, 20H), 7.27 Ad, Jˆ
8.47 Hz, 2H), 7.31 Ad, Jˆ8.17 Hz, 2H), 7.38±7.43 Am,
8H), 7.47 Ad, Jˆ8.2 Hz, 2H), 7.51 Ad, Jˆ8.2 Hz, 2H),
7.83±7.85 Am, 4H), 7.91±8.01 Am, 8H), 8.06 Am, 4H). 13C
NMR Appm) A100 MHz, CDCl3) 61.7, 65.9, 65.9, 656.0,
66.0, 66.4, 70.4, 70.5, 70.7, 70.8, 74.8, 74.9, 114.5, 118.6,
118.6, 118.7, 124.6, 124.8, 127.3, 127.4, 127.7, 127.7,
128.1, 129.9, 130.0, 130.2, 130.3, 130.3, 130.4, 131.8,
4.1.10. +AllylO2C)4[G-2]±CH2Br +3c). Carbon tetra-
bromide ACBr4) A1.53 g, 4.63 mmol) and triphenylphos-
phine A1.21 g, 4.61 mmol) were added to a solution of
AallylO2C)4[G-2]±CH2OH A3b) A2.50 g, 2.31 mmol) in
THF A12.5 mL). After 5 min at room temperature, the
mixture was partitioned between water A20 mL) and
CH2Cl2 A50 mL). The aqueous phase was extracted with
CH2Cl2 A4£50 mL) and the combined organic phases were
dried AMgSO4), and concentrated in vacuo. Puri®cation by
¯ash chromatography ASiO2) A50!100% CH2Cl2/hexanes)
affording 3c as a white solid A2.35 g, 2.05 mmol, 89%).

9400
J. G. Weintraub et al. / Tetrahedron 57 *2001) 9393±9402
132.4, 132.6, 142.3, 142.4, 143.1, 143.3, 146.6, 151.6,
151.8, 166.3, 166.4. IR Aneat ®lm): 2923, 1719 cm21. MS
for C137H124O31Na AM1Na) AMALDI-TOF) calcd 2289.42;
obsd 2289.9. Anal. calcd for C137H124O31: C, 72.60; H, 5.51.
Found: C, 72.45; H, 5.49.
1.2 M solution of NAC4H9)3/HCO2H A1:1) in THF. The
mixture was then heated to 558C for 20 h and the solvent
was removed in vacuo. The oily residue was dissolved in
CH2Cl2 A10 mL) and washed with water A10 mL). The
CH2Cl2 layer was concentrated in vacuo and the resultant
yellow solid was dissolved in 20 mL of 5% aqueous
NaHCO3 and washed with 20 mL diethyl ether. The
aqueous layer was diluted to 50 mL with water and acidi®ed
with concentrated hydrochloric acid to pH 2 causing a preci-
pitate to formwhich was ®ltered, washed with two portions
of deionized water A10 mL) and dried for 12 h in a vacuum
dessicator A0.1 mmHg) over P2O5 affording dendrimer 6b as
a white solid A0.1005 g, 0.045 mmol, 88%). Mpˆ167±
4.1.13. +AllylO2C)8[G-3]±CH2Br +4c). AAllylO2C)8[G-3]±
CH2OH A0.38 g, 0.17 mmol) was converted to AallylO2C)8
[G-3]±CH2Br A4c) using CBr4 A0.17 g, 0.5 mmol) and
triphenylphosphine A0.14 g, 0.5 mmol) in THF A2 mL) as
described for 3c. Puri®cation by ¯ash chromatography
ASiO2) A50!100% CH2Cl2/hexanes) afforded 4c as a clear
glass A0.30 g, 0.13 mmol, 76%). 1H NMR A400 MHz,
CDCl3) d 4.37 As, 2H), 4.74±4.82 Am, 16H), 4.89 As, 2H),
4.91 As, 4H), 5.00 As, 2H), 5.02±5.12 Am, 20H), 5.22±5.28
Am, 8H), 5.33±5.44 Am, 8H), 5.93±6.07 Am, 8H), 6.64 Ad,
Jˆ7.9 Hz, 1H), 6.76±7.15 Am, 20H), 7.23±7.45 Am, 16H),
7.9±8.2 Am, 16H). 13C NMR Appm) A100 MHz, CDCl3) 29.1,
65.9, 65.9, 66.0, 66.0, 66.1, 66.2, 66.5, 70.5, 70.6, 70.7,
70.7, 74.7, 74.8, 74.9, 114.7, 118.6, 118.7, 118.7, 118.7,
127.4, 127.4, 127.5, 127.7, 128.2, 130.0, 130.0, 130.1,
130.2, 130.3, 130.3, 130.4, 132.7, 132.7, 132.7, 142.4,
142.4, 143.2, 143.2, 151.8, 151.8, 151.8, 166.3, 166.3,
1
1748C Awater). H NMR A400 MHz, DMSO-d6) d 4.20±
4.66 Am, 6H), 5.05±5.10 Am, 16H), 5.24±5.26 Am, 8H),
5.64 As, 2H), 6.82±7.15 Am, 20H), 7.39±7.43 Am, 8H),
7.55±7.58 Am, 8H), 7.75±7.95 Am, 24H), 12.94 Abs, 8H).
13C NMR Appm) A100 MHz, DMSO-d6) 59.7, 65.2, 71.1,
75.2, 80.9, 82.7, 116.2, 116.3, 122.9, 123.3, 123.4, 126.0,
129.0, 129.0, 129.1, 129.5, 129.5, 130.9, 130.9, 130.9,
131.1, 131.8, 131.9, 131.9, 133.0, 133.3, 143.5, 143.9,
147.3, 147.4, 152.9, 163.9, 164.2, 166.4, 166.8, 168.4,
168.6, 168.7, 168.7. IR Aneat ®lm): 2966, 1718 cm21
.
HRMS for C126H100O37Na AM1Na) Aelectrospray) calcd
2229.1555; obsd 2229.3063.
166.3, 166.4. IR Aneat ®lm): 1721 cm21
.
MS for
C137H123BrO30Na AM1Na) AMALDI-TOF) calcd 2351.7;
obsd 2351.0. Anal. calcd for C137H123BrO30: C, 70.64; H,
5.32; Found: C, 70.39, H, 5.31.
4.1.16. +AllylO2C)16[G-2]±dendrimer +7a). AAllylO2C)4
[G-2]±CH2Br A3c) A0.67 g, 0.58 mmol) was converted to
AAllylO2C)16[G-2]±dendrimer A7a) using 5 A87.5 mg,
4.1.14. +AllylO2C)8[G-1]±dendrimer +6a). AAllylO2C)2
[G-1]±CH2Br A2g) A207 mg, 0.38 mmol), 5 A54.6 mg,
0.085 mmol), ®nely powdered K2CO3 A140 mg, 1.01
mmol), and 18-C-6 A10.4 mg, 0.039 mmol) were dispersed
in 4:1 THF/DMF A1.0 mL) and heated to 708C. After 14 h,
the solvent was removed in vacuo, and the resultant residue
was partitioned between CH2Cl2 A5 mL), and water A5 mL).
The aqueous phase was then separated and extracted with
CH2Cl2 A3£5 mL). The combined organic layers were dried
AMgSO4) and concentrated in vacuo producing a white
solid. Puri®cation by ¯ash chromatography ASiO2) A5%
diethyl ether/CH2Cl2) afforded 6a as a white solid
A169 mg, 0.067 mmol, 79%). Mpˆ52±608C. 1H NMR
A400 MHz, CDCl3) d 4.71 Abs, 6H), 4.74±4.83 Am, 16H),
5.04 Ad, Jˆ10.8 Hz, 8H), 5.14±5.17 Am, 16H), 5.24±5.30
Am, 8H), 5.35±5.43 Am, 8H), 5.73 As, 2H), 5.96±6.09 Am,
8H), 6.84 Ad, Jˆ8.6 Hz, 4H), 6.89 Ad, Jˆ8.6 Hz, 4H), 6.96±
7.03 Am, 12H), 7.41±7.37 Am, 8H), 7.48±7.51 Am, 8H),
7.94±7.98 Am, 12H), 8.01±8.07 Am, 12H). 13C NMR
Appm) A100 MHz, CDCl3) 64.2, 65.8, 65.9, 66.0, 66.1,
70.8, 75.1, 79.8, 82.54, 114.7, 114.9, 118.6, 118.8, 122.0,
122.3, 122.8, 125.0, 127.4, 128.2, 130.2, 130.3, 130.4,
131.1, 131.2, 132.3, 132.4, 132.6, 132.6, 142.3, 142.9,
146.5, 151.9, 162.9, 163.3, 165.7, 166.3. IR Aneat ®lm):
1718 cm21. MS for C150H132O137Na AM1Na) AMALDI-
TOF) calcd 2547.8; obsd 2546.2. Anal. calcd for
C150H132O37: C, 71.30; H, 5.27; Found: C, 70.95, H, 5.35.
0.135 mmol), freshly powdered K2CO3 A0.15 g, 1.1 mmol),
18-C-6 A8.3 mg, 0.031 mmol) in 3:1 THF/DMF A12 mL) at
708C for 14 h as described for dendrimer 6a. Puri®cation by
¯ash chromatography ASiO2) A5% diethyl ether/CH2Cl2)
afforded 7a as white solid A0.30 g, 0.062 mmol, 46%).
Mpˆ47±578C ACH2Cl2/diethyl ether). 1H NMR A400
MHz, CDCl3) d 4.64 Abs, 6H), 4.79 Am, 32H), 4.89±5.2
Am, 56H), 5.23±5.43 Am, 32H), 5.64 As, 2H), 5.93±6.09
Am, 16H), 6.65±7.05 Am, 36H), 7.26±7.48 Am, 40H),
7.82±8.05 Am, 40H). 13C NMR Appm) A100 MHz, CDCl3)
65.9, 66.0, 66.0, 66.0, 66.4, 70.6, 70.7, 70.8, 74.7, 74.9,
114.5, 114.8, 118.6, 118.7, 118.7, 118.7, 124.9, 127.4,
127.4, 127.7, 128.2, 130.0, 130.1, 130.2, 130.3, 130.4,
131.8, 132.6, 132.6, 132.7, 132.7, 142.3, 143.1, 143.3,
146.6, 151.8, 152.1, 166.2, 166.3. IR Aneat ®lm):
1720 cm21. MS for C294H260O69Na AM1Na) AMALDI-
TOF) calcd 4920.07; obsd 4918.2. Anal. calcd for
C294H260O69: C, 72.11; H, 5.35. Found: C, 72.27, H, 5.32.
4.1.17. +HO2C)16[G-2]±dendrimer +7b). AAllylO2C)16
[G-2]±dendrimer A7a) A210 mg, 0.043 mmol) was converted
to AHO2C)16[G-2]±dendrimer A7b) A148 mg, 0.035 mmol,
81%) as a white solid as described for 6b. Mpˆ151±
1
1728C Awater). H NMR A400 MHz, DMSO-d6) d 4.63±
4.68 Am, 6H), 4.94±5.33 Am, 56H), 5.66 As, 2H), 6.73±
7.17 Am, 44H), 7.35±7.61 Am, 32H), 7.82±8.23 Am, 40H),
12.96 Abs, 16H). 13C NMR Appm) A100 MHz, DMSO-d6)
65.7, 70.6, 70.7, 74.9, 75.0, 115.3, 115.6, 115.7, 122.3,
122.8, 125.3, 125.5, 128.5, 128.5, 128.6, 129.0, 130.4,
130.5, 130.6, 130.7, 131.2, 131.3, 131.4, 131.4, 132.0,
132.7, 132.8, 143.0, 143.1, 143.5, 146.6, 147.0, 152.2,
152.4, 152.6, 163.7, 166.3, 168.3. IR Aneat ®lm): 2975,
4.1.15. +HO2C)8[G-1]±dendrimer +6b). Pd2Adba)3´CHCl3
A24.7 mg, 0.024 mmol) and triphenylphosphine A62.8 mg,
0.239 mmol) were mixed in THF A2.2 mL) and stirred at
ambient temperature until the solution became bright yellow
and homogeneous Aca. 5 min). AAllylO2C)8[G-1]±dendrimer
6a A0.13 g, 0.051 mmol) was dissolved in a portion of this
solution A0.58 mL, 0.0059 mmol,) and 1 mL of a pre-formed
1690 cm21. MS for C2 6H193O69 AM23H/3e) AQ-TOF
4
electrospray) calcd 1417.71; obsd 1418.45.

J. G. Weintraub et al. / Tetrahedron 57 *2001) 9393±9402
9401
B. L.; Smith, J. C. Macromolecules 1998, 31, 815. Ae) Topp,
A.; Bauer, B. J.; Tomalia, D. A.; Amis, E. J. Macromolecules
1999, 32, 7232. Af) Kao, H.-M.; Stefanescu, A. D.; Wooley,
K. L.; Schaefer, J. Macromolecules 2000, 33, 6214.
Ag) Naidoo, K. J.; Hughes, S. J.; Moss, J. R. Macromolecules
1999, 32, 331.
4.1.18. +AllylO2C)16[G-3]±dendrimer +8a). AAllylO2C)8
[G-3]±CH2Br A4c) A150 mg, 0.065 mmol) was converted
to AAllylO2C)16[G-3]±dendrimer A8a) using 5 A10.3 mg,
0.016 mmol), freshly powdered K2CO3 A20 mg,
0.15 mmol), 18-C-6 A11 mg, 0.042 mmol) in 3:1 THF/
DMF A2 mL) at 708C for 14 h as described for dendrimer
6a. Puri®cation by ¯ash chromatography ASiO2) A0!10%
diethyl ether/CHCl3) afforded 8a as white solid A77 mg,
3. Bosman, A. W.; Janssen, H. M.; Meijer, E. W. Chem. Rev.
1999, 99, 1665.
1
4. For an example of a dynamically ordered dendrimer see:
Aa) Huang, B.; Parquette, J. R. J. Am. Chem. Soc. 2001, 123,
2689. Ab) Recker, J.; Tomcik, D. J.; Parquette, J. R. J. Am.
Chem. Soc. 2000, 122, 10298.
8.0 mmol, 51%). Mpˆ50±908C ACHCl3/diethyl ether). H
NMR A400 MHz, CDCl3) d 4.63 Abs, 6H), 4.71±4.84 Am,
64H), 4.94±5.19 Am, 120H), 5.20±5.44 Am, 64H), 5.63 Abs,
2H), 5.97±6.10 Am, 32H), 6.71±7.04 Am, 92H), 7.20±7.41
Am, 64H), 7.75±8.05 Am, 72H). 13C NMR Appm) A100 MHz,
CDCl3) 65.8, 65.9, 66.0, 66.0, 66.0, 66.8, 70.5, 70.6, 70.7,
74.8, 114.4, 118.5, 118.6, 118.6, 118.7, 118.7, 127.3, 127.4,
127.6, 127.7, 128.1, 128.1, 129.9, 130.0, 130.1, 130.2,
130.3, 130.4, 131.8, 132.6, 142.3, 142.4, 143.1, 143.4,
146.2, 151.8, 151.9, 166.3. IR Aneat ®lm): 1722 cm21. MS
for C582H516O133Na AM1Na) AMALDI-TOF) calcd 9661.14;
obsd 9664.9. Anal. calcd for C582H516O133: C, 72.53; H,
5.40. Found: C, 72.20, H, 5.40.
5. For some reviews of chiral dendrimers, see: Aa) Seebach, D.;
Rheiner, P. B.; Greiveldinger, G.; Butz, T.; Sellner, H. Top.
Curr. Chem. 1998, 197, 125. Ab) Peerlings, H. W. I.; Meijer,
E. W. Chem. Eur. J. 1997, 3, 1563. Ac) Thomas, C. W.; Tor, Y.
Chirality 1998, 10, 53. For some recent examples, see:
Ad) Gong, L.-Z.; Hu, Q.-S.; Pu, L. J. Org. Chem. 2001, 66,
2358. Ae) Reuter, C.; Pawlitzki, G.; Worsdorfer, U.; Plevoets,
M.; Mohry, A.; Kubota, T.; Okamoto, Y.; Vogtle, F. Eur. J.
Org. Chem. 2000, 3059. Af) Turrin, C.-O.; Chiffre, J.; Daran,
J.-C.; de Montauzon, D.; Caminade, A.-M.; Manoury, E.;
Balavoine, G.; Majoral, J.-P. Tetrahedron 2001, 57, 2521.
6. Aa) Kremers, J. A.; Meijer, E. W. J. Org. Chem. 1994, 59,
4262. Ab) Peerlings, H. W. I.; Strunk, M. P.; Meijer, E. W.
Chirality 1998, 10, 46. Ac) Rosini, C.; Superchi, S.; Peerlings,
H. W. I.; Meijer, E. W. Eur. J. Org. Chem. 2000, 61.
7. Peerlings, H. W. I.; Trimbach, D. C.; Meijer, E. W. Chem.
Commun. 1998, 497.
4.1.19. +HO2C)32[G-3]±dendrimer +8b). AAllylO2C)16
[G-3]±dendrimer A8a) A63 mg, 6.5 mmol) was converted to
AHO2C)32[G-3]±dendrimer A8b) A0.035 g, 4.19 mmol, 65%)
as a waxy white solid as described for 6b. Mpˆ165±1808C
1
Awater). H NMR A400 MHz, DMSO-d6) d 4.53±4.58 Am,
6H), 4.76±5.22 Am, 120H), 5.59 As, 2H), 6.82±7.23 Am,
92H), 7.32±7.55 Am, 64H), 7.67±8.17Am, 72H), 12.88 Abs,
32H). 13C NMR Appm) A100 MHz, DMSO-d6) 65.3, 65.8,
69.7, 74.1, 113.9, 114.1, 114.5, 124.4, 124.6, 127.5, 127.7,
127.7, 127.7, 128.1, 129.4, 129.5, 129.6, 129.7, 129.8,
130.3, 130.4, 130.5, 131.2, 131.8, 142.2, 142.7, 145.6,
151.4, 151.4, 151.5, 151.6, 167.4. IR Aneat ®lm): 2972,
8. Aa) Murat, M.; Grest, G. S. Macromolecules 1996, 29, 1278.
Ab) Welch, P.; Muthukumar, M. Macromolecules 1998, 31,
5892.
9. Aa) De Backer, S.; Prinzie, Y.; Verheijen, W.; Smet, M.;
Desmedt, K.; Dehaen, W.; De Schryver, F. C. J. Phys.
Chem. A 1998, 102, 5451. Ab) Gitsov, I.; Frechet, J. M. J. J.
Am. Chem. Soc. 1996, 118, 3785. Ac) Stechemesser, S.; Eimer,
W. Macromolecules 1997, 30, 2204. Ad) Topp, A.; Bauer, B. J.;
Tomalia, D. A.; Amis, E. J. Macromolecules 1999, 32, 7232.
10. Naylor, A. M.; Goddard, W. A. I.; Kiefer, G. E.; Tomalia,
D. A. J. Am. Chem. Soc. 1989, 111, 2339. For an example
of a dendrimer that folds in a solvent-dependent manner, see
Ref. 4.
1691 cm21
.
Acknowledgements
This work was supported by the National Science Founda-
tion CAREER programACHE-98-75458) and acknowledge-
ment is made to the donors of the Petroleum Research Fund,
administered by the American Chemical Society, for partial
support of this work.
11. Seebach observed a variation in the sign and shape of the CD
spectra with dendrimer generation that occurred in a poor
solvent, acetonitrile, but not in a good solvent such as
dichloromethane. Murer, P.; Seebach, D. Helv. Chim. Acta
1998, 81, 603.
References
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Chirality 2001, 13, 24.
È
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14. For
a preliminary communication of this work, see:
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J. G. Weintraub et al. / Tetrahedron 57 *2001) 9393±9402
17. We have observed a decrease in CD intensity and optical
rotation in analogous 3,5-branched dendrimers. This decrease
was corollated with an increasing steric effect that perturbs the
conformational equilibrium of the central core rather than
contributions fromchiral conforamtions in the branch
segments. See Chaumette, J.-L.; Laufersweiler, M. J.;
Parquette, J. R. J. Org. Chem. 1998, 12, 16.
18. Prepared by reduction of 2a with NaBH4 followed by
hydrolysis of the methyl esters with sodium hydroxide.