Synthesis of new cores and their use in the preparation of polyester dendrimers

Article abstract of DOI:10.1016/j.tet.2010.10.018

Six dendrimer and dendron cores terminated by hydroxyl groups that are neither phenolic nor cleavable by hydrogenolysis have been prepared in a consistent one-pot manner from terminal allyl groups by reduction of the product of reductive ozonolysis. Some of the terminal allyl derivatives are new and others have been prepared by new methods. The well-known O-benzylidene derivative of 2,2′-bis(hydroxymethyl)propanoic acid was shown to be the cis-stereoisomer. A new AB₃-type anhydride, tris(benzyloxymethyl) acetic anhydride has been prepared. It was demonstrated that these cores and dendrons could be assembled into first and second generation homo- and mixed polyester dendrimers.

Full text of DOI:10.1016/j.tet.2010.10.018

Tetrahedron 66 (2010) 9602e9609
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of new cores and their use in the preparation of polyester dendrimers
,
,
Jean-d’Amour K. Twibanire a, Hussein Al-Mughaid a b, T. Bruce Grindley a
*
a Department of Chemistry, Dalhousie University, Halifax, N.S., Canada B3H 4J3
b Applied Chemical Sciences, Jordan university of Science and Technology, PO Box 3030, Irbid 22110, Jordan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 August 2010
Received in revised form 7 October 2010
Accepted 8 October 2010
Available online 14 October 2010
Six dendrimer and dendron cores terminated by hydroxyl groups that are neither phenolic nor cleavable
by hydrogenolysis have been prepared in a consistent one-pot manner from terminal allyl groups by
reduction of the product of reductive ozonolysis. Some of the terminal allyl derivatives are new and
others have been prepared by new methods. The well-known O-benzylidene derivative of 2,20-bis(hy-
droxymethyl)propanoic acid was shown to be the cis-stereoisomer. A new AB3-type anhydride, tris
(benzyloxymethyl)acetic anhydride has been prepared. It was demonstrated that these cores and den-
drons could be assembled into first and second generation homo- and mixed polyester dendrimers.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Polyester dendrimers have attracted interest1e9 because they are
non-toxic but are labile enough in vivo to release any biologically
active units either covalently attached or encapsulated.9e11 As part
of a program to prepare glycodendrimers,12 we desired aromatic
cores with non-phenolic hydroxyl groups for ester stability that
would not be cleaved under hydrogenolysis conditions. We selected
the molecules 1e6 as synthetic targets. None of these cores have
previously been used for the preparation of polyester dendrimers.
Because these compounds all have terminal CH2CH2OH groups, we
chose to employ one route for their synthesis that could be used for
all: reduction of the products of reductive ozonolysis of allyl groups.
This approach had not been used before to prepare any of these
compounds and it proved to be convenient and high yielding. In
addition, we demonstrate the use of some of these cores through the
synthesis of second generation polyester dendrimers using both
a well-known divalent dendron and a new dendron of the AB3-type.
2.1. Synthesis of new cores
1,4-Benzenediethanol (1) had been prepared previously by Clark
and O’Reilly using the reaction of the Grignard reagent obtained
from 1,4-dibromobenzene with ethylene oxide.13 However, the
yield reported was 52% and ethylene oxide, a toxic gas, is both
expensive and inconvenient to handle on a laboratory scale. It has
also been prepared in impure form by reduction of 1,4-phenyl-
enediacetic acid, a relatively costly starting material with LAH.14
Our initial approach via the diallyl derivative 8 is shown in
Scheme 1. Steiger et al. reported the synthesis of 8 in 32% yield via
coupling of the bis Grignard reagent of 1,4-dibromobenzene with
allyl bromide.15 In our hands, 8 was always accompanied by the
monoadduct 7, even after chromatography. Performing the reaction
in two separate steps did not improve the yield; reaction of the
mono Grignard reagent with allyl bromide gives 716 in 63% yield in
our hands and the yield for conversion of 7 to 8 under the same
conditions was similar (59%).
OH
OH
OH
O
O
1
2
3
HO
Br
OH
OH
HO
H
1. Mg (2.2 eq)
/ THF
1. O3
O
NaBH4
59%
Br
Br
OH
OH
OH
O
1
O
heat
O
2. Me2S
60%
H
8 52%
O
OH
9
HO
I
O
O
2. excess
Br
+
4
5
6
Br
heat
7
9%
Scheme 1. Initial synthesis of 1,4-benzenediethanol (1).
* Corresponding author. E-mail address: bruce.grindley@dal.ca (T.B. Grindley).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.018

J. K. Twibanire et al. / Tetrahedron 66 (2010) 9602e9609
9603
An alternative route to 1,4-diallylbenzene (8) proved to be cost
effective and high yielding. The copper-catalyzed coupling of vinyl
magnesium bromide with the known diiodide 1017 gave a good yield
of the diallyl derivative 8 in 1 h at 0 ꢀC. Compound 10 has also been
made in excellent yield by performing Stille coupling of the bistriflate
of hydroquinone with tributylallylstannane in the presence of
PdCl2(PPh3)2 (20 mol %) and LiCl.18 Conversion to 1 via reductive
ozonolysis followed by the same-pot reduction proceeded in good
yield (Scheme 2).
involving displacement of methyl bromoacetate by phenoxide,35
followed by reduction has also been used for 6.36
The reduction of the products of reductive ozonolysis of allyl
ethers yielded the remaining cores 3,37 4,26,38 5,39 and 6,22 in ex-
cellent yields (see Scheme 4). The required allyl ethers were
obtained in 10e15 min at ꢁ10 to ꢁ15 ꢀC by reaction of the phen-
oxide anions with allyl bromide in DMF.
1. O3
2. Me2S
OH
O
Br
NaH
DMF
3. NaBH4
3
MgBr
Cl
I
79%
1. O3
2. Me2S
-10 oC, 15 min
99%
CuI (10 mol %),
NaI
12
acetone
2,2'-dipyridyl (10 mol %),
OH
O
1
65 oC-70 o
95%
C
THF, 0 oC
81%
3. NaBH4
79%
1. O3
2. Me2S
3. NaBH4
OH
O
Cl
I
Br
8
10
NaH
4
Scheme 2. Improved synthesis of 1,4-benzenediethanol (1).
DMF
-15 oC, 15 min
97%
79%
Br
Br
13
Two groups had reported the synthesis of 1,3,5-benzene-
triethanol (2) by quite different methods. Cochrane et al.19 prepared
it by reduction of triethyl 1,3,5-benzenetriacetate.20 The precursor
1,3,5-benzenetriacetic acid was made from 1,3,5-triacetylbenzene
using the Kindler modification of the Willgerodt reaction20 and
1,3,5-triacetylbenzene can be prepared by an acid-catalyzed tri-
merization of formyl acetone,21 overall a four-step process. Brad-
shaw and Krakowiak used the same method but chose to reduce
the precursor triacid in 45% yield.22 An alternative one-pot syn-
thesis of 2 gave a non-separated mixture of tris-(2-hydroxyethyl)
benzenes using a cobalt-catalyzed trimerization of 3-butyn-1-ol
but the starting material is expensive and the separation is im-
practical.23 A reaction scheme analogous to Scheme 2 could not be
followed because the required precursor, 1,3,5-tris(chloromethyl)
benzene, is not commercially available. An attempt was made to
prepare 1,3,5-triallylbenzene (11) from 1,3,5-tribromobenzene via
the Grignard method but it gave unseparable mixtures of partially
allylated derivatives along with the desired product.
1. O3
O
OH
2. Me2S
Br
NaH
3. NaBH
4
5
78%
DMF
-15 oC, 15 min
96%
I
I
14
1. O3
O
2. Me2S
3. NaBH4
6
O
69 %
O
15
Allylation of aromatic halides with allyltributyltin24 in the
presence of tetrakis(triphenylphosphine)palladium(0) has been
known for more than 30 years.25 The triple version of this reaction
worked well with 1,3,5-tribromobenzene on scales of <10 g as
shown in Scheme 3. The product (11) was converted to the desired
triol 2 as described above in the synthesis of 1.
Scheme 4. The synthesis of 2-hydroxyethoxy derivatives 3e6.
2.2. Synthesis of dendrons
A number of research groups have synthesized and utilized
16,40e44 apparently as a single isomer, but its configuration has not
been established as far as we are aware. Two stereoisomers of 16 are
possible as shown in Fig. 1. 1H NMR and 13C NMR spectra of 16
showed that a single isomer had also been isolated here (Scheme 5),
not the mixture of cis- and trans-isomers expected based on the free
energy difference for the isomers of 5-carboxymethyl-2-isopropyl-
5-methyl-1,3-dioxane.45
Br
Br
1. O3
2. Me2S
3. NaBH4
Pd(Ph P)
benze3ne,4
reflux
Br
+
2
78%
24 h
75%
11
Bu3Sn
O
OH
Scheme 3. The synthesis of 1,3,5-triallylbenzene (11) and 1,3,5-benzenetriethanol (2).
HO
O
O
Ph
Ph
O
O
O
trans
cis
2-Hydroxyethoxy derivatives of aromatic compounds, such as
3e6, have been made in a variety of ways. Compounds 3 and 4 were
originally prepared by reaction of the sodium salts of the phenols
with 2-chloroethanol26 and 2-bromoethanol has also been used.27
The patent literature contains numerous reports of the formation of
3 by reaction of the dianion with ethylene oxide. Compound 5 has
been made by iodination of 2-hydroxyethoxybenzene.28e30 Sur-
prisingly, 6 has commonly been made from phloroglucinol by re-
action with ethylene carbonate in DMF at 150 ꢀC in the presence of
tetrabutylammonium bromide.31 Although this is a one-step re-
action, it suffers from low yields, values of between 20 and 37%
have been reported.22,32e34 An alternative two-step approach
Fig. 1. cis- and trans-Isomers of 5-methyl-2-phenyl-1,3-dioxane-5-carboxylic acid (16).
O
O
O
OH
H
O
Ph
O
HO
HO
H2O
HCl
O
DCC
+
17
CH2Cl2
91%
O
O
O
O
O
O
HO
16
Ph
Ph Ph
Scheme 5. Preparation of anhydride 17.

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J. K. Twibanire et al. / Tetrahedron 66 (2010) 9602e9609
Piasecki et al.46e48 synthesized a series of 1,3-dioxanes bearing
various long chain alkyl substituents at C-2 and a methyl group and
a carboxyl group at C-5. The C-5 methyl protons in these compounds
absorbed as singlets at 1.02 ppm. Eliel and Enanozahad noted that an
axially-oriented eCH3 at C-5 (chemical shifts w1.5e1.6 ppm in 5-
methyl-2-substituted-1,3-dioxanes) is deshielded by 0.5e0.6 ppm
with respect to an equatorially-oriented eCH3 (chemical shifts
w1 ppm).45 In addition, in isomers with the eCH3 and the C-2 group
cis-, the chemical shift difference between the signals of the equa-
torial and axial protons at C-4,6 is negligible or small,45 whereas in
the trans-isomer it is large, about 1 ppm for those prepared by Pia-
secki et al.47 For 16, the methyl group absorbed at 1.11 ppmwhen the
samplewas run in chloroform-d orat 1.05 ppmwhen the samplewas
run in acetone-d6. The chemical shift difference between the two
protons on C-4,6 was 0.91 ppm in chloroform-d and 0.83 ppm in
acetone-d6. Based on these grounds, 16 is the cis-isomer (Fig. 1).
Surprisingly, the sample of 16 prepared here and recrystallized from
ethyl acetate had a different mp 149e151 ꢀC than those previously
reported, 185e187 ꢀC from acetone,42 and 197e198 ꢀC from
dichloromethane.41 All three samples where mps were reported
were clearly the same isomer because the two 1H NMR-based cri-
teria for isomer structure were the same: the reported chemical
shifts of the methyl in the same solvent agreed within 0.02 ppm and
the reported chemical shift differences between the equatorial and
axial protons on C-4,6 were between 0.83 and 1.0 ppm in different
solvents. The same isomer was also prepared in those papers where
mps were not reported40,43 as indicated by the two NMR criteria
mentioned above. Presumably, different polymorphs are obtained
under different recrystallization conditions.
O-benzylpentaerythritol (19) as shown in Scheme 6. This approach
avoids the use of excess benzyl bromide required for the direct
synthesis of 19 from pentaerythritol.52,53 Jones oxidation of 19 gave
carboxylic acid 20, that was converted to crystalline anhydride 21
with DCC.
2.3. Dendrimer synthesis
As shown in Schemes 7 and 8, cores 1 and 3 reacted with an-
hydride 17 in the presence of DMAP and pyridine to give protected
first generation dendrimers 22 and 24 in excellent yield. Depro-
tection by hydrogenolysis also proceeded in excellent yield to give
the deprotected first generation dendrimers 23 and 25. The same
two steps with 25 and 17 gave the deprotected second generation
dendrimers 27 (Scheme 9).
HO
HO
O
Ph
O
O
O
O
OH
OH
O
DMAP
DCM
pyridine
Pd/ C, H2
17
+
DCM/ MeOH/
THF
97%
99%
1
O
O
O
O
O
OH
OH
Ph
O
Kaloustian et al. attributed the axial preference at C-5 of 1,3-
dioxanes for positively charged groups, such as the trimethy-
lammonium group, on the electrostatic attraction of the resultant
CeO dipole and the CeNþ dipole in this geometric arrangement
and suggested that the small conformational effect of a carbonyl
group at C-5 had a contribution from the same effect.49 However,
a similar favoring of the axial orientation for 5-fluoro derivatives
must arise from the gauche effect,50 where bonding interactions
favor gauche arrangements and dipoleedipole repulsion disfavors
them. Piasecki and Rucha1a found that formation of the acetal in
non-polar solvents, such as hexane gave mixtures whereas for-
mation in polar solvents, such as acetonitrile gave only the cis-
isomer,48 consistent with the measured effects of solvent polarity
on conformational equilibria and with decrease of through space
dipoleedipole repulsion in polar solvents.49 16 was prepared here
in a polar solvent, water, and only the cis-isomer was observed but
preparations of 16 in non-polar solvents gave the same isomer 40e44
(see above).
22
23
Scheme 7. Preparation of first generation dendrimer 23, a tetraol.
O
O
O
O
OH
OH
O
OH
O
DMAP
DCM
O
O
O
O
O
Ph
pyridine
Pd/ C, H2
17
+
25
DCM/ MeOH/
THF
94%
O
96%
3
Ph
OH
OH
OH
O
O
O
24
O
O
O
Acid 16 was converted into the anhydride 17 as earlier,43 using
N,N0-dicyclohexylcarbodiimide (DCC) (Scheme 5).
Scheme 8. Preparation of first generation dendrimer 25, another tetraol.
A symmetrical dendron 20 that could provide three branching
points, that is, an AB3 dendron, was prepared by selective reduction
of known51 di-O-benzyl-O-benzylidenepentaerythritol (18) to tri-
The AB3 anhydride 21 reacted with core 3 under the standard
conditions to give a protected first generation dendrimer in ex-
cellent yield. Hydrogenolysis of the six O-benzyl groups occurred
on reaction overnight under the same conditions used for removal
of the benzylidene acetals (Scheme 10). Reaction of the product
hexaol 29 with anhydride 17, followed by hydrogenolysis gave the
second generation mixed polyester dendrimer 31, again in excellent
yield (Scheme 11).
OBn
OBn
OBn
BnO
HO
O
CoCl2, BH3.THF
O
THF, rt
91 %
OBn
18
19
Jones reagent
acetone, 8h
74 %
3. Conclusions
O
O
O
BnO
BnO
BnO
OBn
OBn
OBn
BnO
BnO
BnO
DCC
In Section 2.1 above, it was demonstrated that one-pot reductive
ozonolysis of allyl derivatives followed by reduction with sodium
borohydride is an efficient general procedure for the production of
terminal CH2CH2OH groups. The allyl groups can be either C-allyl or
O-allyl groups. The latter are readily accessible and a variety of
O
OH
20
21
DCM, 8h
89 %
Scheme 6. Preparation of anhydride 21.

J. K. Twibanire et al. / Tetrahedron 66 (2010) 9602e9609
9605
strageties have been employed for the introduction of one to three
C-allyl groups onto aromatic rings.
O
O
OH
OH
O
O
NMR parameters established that the configuration of the well-
known O-benzylidene derivative of 2,20-bis(hydroxymethyl)prop-
anoic acid was cis. A new AB3-type anhydride, tris(benzyloxy-
methyl)acetic anhydride (21) has been prepared. It was shown
that the divalent diol cores 1 and 3 could be used with known
anhydride 17 and new AB3 anhydride 21 to produce homogeneous
and heterogeneous second generation polyester dendrimers.
Deprotection via hydrogenolysis proceeds readily with these
products to give clean polyols.
O
O
Ph
O
O
Ph
O
O
O
O
OH
OH
O
O
O
O
DMAP
DCM
O
O
O
O
25
pyridine
Pd/ C, H2
+
27
DCM/ MeOH/
THF
92%
17
97%
O
O
O
OH
OH
O
O
O
4. Experimental section
4.1. General
O
O
Ph
Ph
O
26
O
O
O
O
OH
OH
O
O
O
1H and 13C NMR spectra were recorded on a Bruker Avance 500
NMR spectrometer operating at 500.13 and 125.7 MHz, re-
spectively, using the solvent resonances as secondary standards.
Coupling constant (J) values are reported in Hertz. High-resolution
mass spectra were recorded on a Bruker Micro-TOF mass spec-
trometer using electrospray ionization except for 11, whose HRMS
were measured on a CEC 21e110B mass spectrometer using elec-
tron ionization (70 eV). Melting points were determined on
a FishereJohn’s melting point apparatus and are uncorrected. Ac-
etone was refluxed over K2CO3 and distilled over molecular sieves.
Dichloromethane was refluxed over calcium hydride and distilled
onto molecular sieves. Benzene was refluxed over CaCl2 and dis-
tilled over molecular sieves. Methanol was refluxed over calcium
oxide and distilled over molecular sieves. Tetrahydrofuran was
refluxed over LiAlH4 and distilled over molecular sieves. Unless
otherwise noted, non-aqueous reactions were carried out under
a nitrogen atmosphere. Jones reagent (0.56 M) was prepared by
dissolving sodium dichromate dihydrate (Na2Cr2O7$2H2O, 300 g,
1.01 mol) in 1.5 L of water followed by slowly adding concd sulfuric
acid (300 mL) to the cooled solution (0 ꢀC). Compounds were lo-
cated by spraying the TLC plate with a solution of 2% ceric ammo-
nium sulfate in 0.5 M H2SO4, followed by heating on a hot plate
until color developed. Solid compounds were purified on silica gel
using flash column chromatography and specified eluents, or by
crystallization. Liquids and oils were purified using flash column
chromatography.
Scheme 9. Preparation of second generation dendrimer 27, an octaol.
OBn
OH
O
O
OBn
OH
O
O
OBn
OH
DMAP
DCM
O
O
O
O
3
pyridine
Pd/ C, H2
29
+
94%
DCM/ MeOH/
THF
21
96%
O
O
OBn
OH
OH
O
O
OBn
28
OBn
OH
Scheme 10. Preparation of first generation dendrimer 29, a hexaol.
4.2. Synthesis of cores
4.2.1. 1-Allyl-4-bromobenzene (7). A stirred mixture of magnesium
turnings (3.62 g, 0.149 mol) and dry THF (150 mL) in a two-neck
round-bottomed flask was flushed with N2 for 10 min then heated
to 40 ꢀC when two drops of 1,2-dibromoethane were added. 10% of
a solution of 1,4-dibromobenzene (29.3 g, 0.124 mol) in THF (50 mL)
was added and when the magnesium had started to react, the rest
of this solution was added slowly over 1 h. Stirring was continued
until magnesium turnings were completely consumed. The flask
was cooled to 0 ꢀC and a solution of allyl bromide (16.5 g, 0.136 mol)
in dry THF (30 mL) was added slowly over 1 h. The mixture was
refluxed for 12 h, then allowed to cool to rt. Water (60 mL) was
carefully added and the mixture was extracted using diethyl ether
(40 mLꢂ3). The combined extracts were dried (MgSO4), filtered,
and concentrated. Purification using column chromatography
(hexanes/EtOAc; 2: 1, Rf 0.44) afforded a colorless syrup (15.4 g, 63%
yield). 1H NMR and 13C NMR data similar to lit.54
O
O
HO
HO
O
O
O
O
OH
OH
O
O
O
O
Ph
Ph
O
O
O
O
O
O
O
O
O
O
O
HO
HO
Ph
O
DMAP
DCM
O
O
29
pyridine
Pd/ C, H2
31
+
97%
DCM/ MeOH/
THF
17
30
O
O
96%
O
O
O
O
O
O
O
OH
OH
O
O
O
O
Ph
Ph
O
O
O
O
HO
HO
O
O
O
O
O
4.2.2. 1,4-Diallylbenzene (8). An oven-dried two-neck round-bot-
tomed flask charged with 10 (48.0 g, 0.134 mol), CuI (2.55 g,
0.013 mol), and 2,20-dipyridyl (2.10 g, 0.013 mol) was evacuated and
flushed with N2. Anhydrous THF (900 mL) was added and the
O
HO
HO
O
Ph
Scheme 11. Preparation of second generation dendrimer 31, a dodecaol.

9606
J. K. Twibanire et al. / Tetrahedron 66 (2010) 9602e9609
stirred reaction mixture was cooled to 0 ꢀC. A 1 M solution of vinyl
magnesium bromide in THF (540 mL, 0.536 mol) was added quickly
via cannula, and the reaction mixture was allowed to warm to rt.
After 1 h, saturated NH4Cl (200 mL) and 28% NH3 (150 mL) were
added and the mixture was stirred for 1 h at rt. The product was
extracted with hexanes (100 mLꢂ3) and the combined extracts
were washed with brine (60 mLꢂ2), dried (MgSO4), filtered, and
concentrated. Purification using column chromatography (hexanes,
Rf 0.37) gave a colorless oily syrup (17.2 g, 81% yield); 1H and 13C
NMR data similar to lit.15,18
diethyl ether (250 mL) and the aqueous layer was extracted with
ether (2ꢂ60 mL). The organic layers were combined, dried
(MgSO4), filtered, and concentrated under vacuum. The product
was obtained as a pale yellow oily liquid and crystallized from
hexanes at ꢁ10 ꢀC to give colorless crystals (34.2 g, 99% yield): mp
38e40 ꢀC; lit.55 mp 31.9e32.4 ꢀC; 13C NMR (125.7 MHz, CDCl3)
d
153.1 (PhC),133.8 (CH]),117.6 (]CH2),115.8 (PhC), 69.6 (CH2); 1H
NMR similar to lit.56
4.2.7. 1,4-Bis-(2-hydroxyethoxy)benzene (3). Prepared from 12
(4.68 g, 0.025 mol) as for 1 and purified using column chroma-
tography (EtOAc; Rf 0.51) to give the product as a colorless crys-
talline powder (3.87 g, 79% yield): mp 102e104 ꢀC; lit.37 mp
103e104 ꢀC.
4.2.3. General method for one pot reductive ozonolysis and re-
duction: 1,4-benzenediethanol (1). Ozone was bubbled through
a solution of 8 (4.65 g, 29.4 mmol) maintained at ꢁ78 ꢀC in a 1:1
mixture of methanol (100 mL) and dichloromethane (100 mL) until
TLC confirmed the disappearance of the olefin. N2 was then bubbled
through the reaction mixture for 15 min. Excess dimethyl sulfide
was added at ꢁ78 ꢀC, and the reaction mixture was allowed to
warm to rt with stirring, then concentrated under vacuum. The
resulting syrup was dissolved in absolute ethanol (100 mL), and the
solution was cooled to 0 ꢀC. Excess NaBH4 was added in portions
with stirring, which was continued at rt for 20 h. Water (20 mL) was
added and the solution was acidified to pH w6 (20% HCl), and the
mixture filtered. Concentration under vacuum gave a thick oily
residue, which was then dissolved in EtOAc (65 mL) and water
(15 mL). The organic layer was collected, dried (MgSO4), and con-
centrated. The product was obtained as a colorless solid and was
purified by column chromatography (EtOAc, Rf 0.52) to give color-
less crystals (3.86 g, 79% yield): mp 84e86 ꢀC; lit.13 mp 85 ꢀC; 1H
4.2.8. 1-Allyloxy-4-bromobenzene (13). Prepared from allyl bro-
mide (70.0 g, 0.580 mol) in anhydrous DMF (200 mL), sodium
hydride (60% oil dispersion, 5.60 g, 0.14 mol), and a solution of 4-
bromophenol (20.0 g, 0.116 mol) in DMF (100 mL) as for 12. The
product was obtained as a colorless oily liquid after purification
using column chromatography (24 g, 97% yield): (EtOAc/hexanes;
1:2, Rf 0.52); 1H NMR and 13C NMR spectra similar to lit.57
4.2.9. 2-(4-Bromophenoxy)ethanol (4). The general method for re-
ductive ozonolysis and reduction with 13 (12.5 g, 0.058 mol) gave
a product as a thick residue that was purified using column chro-
matography (EtOAc, Rf 0.31). The product solidified on cooling to give
colorless crystals (10 g, 79% yield): mp 54e56 ꢀC; lit.26 mp 55 ꢀC.
NMR similar to lit.; 13C{1H} NMR (125.7 MHz, CDCl3)
129.4 (PhCH), 63.8 (CH2O), 39.0 (CH2Ph).
d
136.8 (qPhC),
4.2.10. 1-Allyloxy-4-iodobenzene (14). The general method for
allylation with allyl bromide (68.7 g, 0.568 mol) in DMF (240 mL),
sodium hydride (60% oil dispersion, 5.45 g, 0.136 mol), and a solu-
tion of 4-iodophenol (25.0 g, 0.114 mol) in DMF (100 mL) gave, after
purification using column chromatography (hexanes, Rf 0.43), 14 as
4.2.4. 1,3,5-Triallylbenzene (11). A sealed tube was charged with
allyltributylstannane24 (3.10 mL, 0.010 mol), 1,3,5-tribromobenzene
(1.00 g, 0.003 mol), tetrakis(triphenylphosphine)palladium(0)
(0.280 g, 7.50 mol %), dry benzene (5 mL), and a stirring bar. The
reaction mixture was stirred under N2 in the sealed tube at a bath
temperature of 120 ꢀC for 24 h. The tube was then allowed to cool to
rt and the pressure was carefully released. Diethyl ether (15 mL)
was added and the mixture was stirred for 15 min with saturated KF
(10 mL). The organic layer was separated and stirred with 10%
NH4OH (10 mL) for 20 min. The organic layer was separated,
washed with brine (10 mL), dried (MgSO4), and concentrated to
give crude triallylbenzene that was distilled (bp 125 ꢀC/1.5 Torr) to
give the pure product as a colorless syrup (0.47 g, 75% yield); 1H
a yellow oil (28.3 g, 96% yield); 1H NMR (500.13 MHz, CDCl3)
d 4.49
(dt, J¼5.0, 1.5 Hz, 2H, OCH2), 5.33 (dq, J¼10.5, 1.5 Hz, 1H, Hcis), 5.44
(dq, J¼17.5, 1.5 Hz, 1H, Htrans), 6.05 (ddt, J¼17.5, 10.5, 5 Hz, 1H,
CH2CH]CH2), 6.69e6.72 (m, 2H, PhH), 7.55e7.58 (m, 2H, PhH); 13
C
NMR (125.7 MHz, CDCl3) d 158.3, 138.1 (PhC), 132.8 (vinyl CH) 117.8
(vinyl CH2), 117.1 (PhCH), 83.0 (PhCI), 68.6 (CH2 sp3); HR EIMS m/z
calcd for C9H9IO 259.9698; found 259.9690. Note that the 1H NMR
data are identical to those of Taskinen58 but neither the 1H NMR or
13C NMR data match those for in the incomplete characterization of
14 provided by Qu et al.59
NMR (500.13 MHz, CDCl3)
(m, 6H, 3CH2CH]CH2), 5.96 (m, 3H, 3CH2CH]CH2), 6.87 (s, 3H,
PhH); 13C NMR (125.7 MHz, CDCl3)
140.3 (PhC), 137.6 (3CH2CH]
d
3.35 (d, J¼6.5 Hz, 6H, 3CH2 sp3), 5.08
4.3. Synthesis of dendrons
d
CH2), 126.6 (PhC), 115.7 (3CH2CH]CH2), 40.2 (3CH2 sp3). HR EIMS
m/z calcd for C15H18 198.1409; found 198.1419.
4.3.1. 5-Methyl-2-phenyl-1,3-dioxane-5-carboxylic acid (16). 2,2-Bis
(hydroxymethyl)propanoic acid (30.0 g, 0.224 mol) was dissolved
in water (300 mL) in a 500 mL round-bottomed flask. Under
vigorous stirring, concd HCl (3 mL) was added, and benzaldehyde
(23.7 g, 0.224 mol) was added dropwise over a period of 2 h at
38 ꢀC. When the addition was complete, stirring was continued
overnight at 40 ꢀC. The reaction mixture was allowed to cool to rt,
and the precipitated solid product was collected using suction
filtration, and was washed with water (2ꢂ50 mL), then crystal-
lized (EtOAc) to give colorless needles (27 g, 54% yield): mp
149e151 ꢀC; lit. mp 185e187 ꢀC,42 197e198 ꢀC;41 1H NMR
4.2.5. 1,3,5-Benzenetriethanol (2). Compound 2 was prepared from
11 (4.26 g, 0.022 mol) by the general method and purified by col-
umn chromatography (EtOAc, Rf 0.48) to give colorless crystals
(3.52 g, 78% yield): mp 74e76 ꢀC; lit.19 mp 75 ꢀC 1H and 13C NMR
data similar to lit.23
4.2.6. General method for forming allyl ethers: 1,4-diallyloxybenzene
(12). Allyl bromide (220 g, 1.82 mol) and anhydrous DMF (200 mL)
were cooled to ꢁ10 ꢀC and sodium hydride (60% oil dispersion,
17.6 g, 0.440 mol) was added. The resulting mixture was stirred for
10 min, and a solution of hydroquinone (20.0 g, 0.182 mol) in DMF
(200 mL) was added dropwise over 30 min. The reaction mixture
was stirred for 15 min after which TLC confirmed the disappearance
of hydroquinone. The flask was allowed to warm to 0 ꢀC and water
(150 mL) was carefully added. The product was extracted with
(500.13 MHz, CDCl3)
d
1.11 (s, 3H, CH3), 3.71 (d, J¼11.5 Hz, 2H, H-
4ax, H-6ax), 4.62 (d, J¼11.5 Hz, 2H, H-4eq, H-6eq), 5.49 (s, 1H, H-2),
7.32e7.37 (m, 3H, PhH), 7.44e7.48 (m, 2H, PhH), 10.6 (br, 1H,
COOH); 1H NMR (500.13 MHz, acetone-d6)
d 1.05 (s, 3H, CH3), 3.74
(d, J¼11.5 Hz, 2H, H-4ax, H-6ax), 4.57 (d, J¼11.5 Hz, 2H, H-4eq, H-
6eq), 5.53 (s, 1H, H-2), 7.31e7.44 (m, 5H, PhH); 13C NMR
(125.7 MHz, acetone-d6):
d 175.7 (C]O), 139.8, 129.4, 128.7, 127.1

J. K. Twibanire et al. / Tetrahedron 66 (2010) 9602e9609
9607
(PhC), 102.1 (C-2), 74.0 (C-4, C-6), 42.6 (C-5), 18.2 (CH3). HR ESI MS
m/z calcd for C12H13O4 221.0819; found 221.0834.
31.1 mmol) were dissolved in dry CH2Cl2 (120 mL) and the mixture
was stirred at rt for 8 h when TLC confirmed the disappearance of
the acid. DCU by-product was filtered off and CH2Cl2 was removed
under vacuum to give 21 as a colorless solid, purified using column
chromatography (hexanes/EtOAc; 3:1; Rf 0.45) to give a colorless
crystalline solid (20.8 g, 89% yield). Recrystallization (MeOH,
ꢁ10 ꢀC) gave colorless crystals: mp 69e70 ꢀC; 1H NMR
4.3.2. 5-Methyl-2-phenyl-1,3-dioxane-5-carboxylic anhydride (17).
Anhydride 17 was synthesized as previously described.42 Carboxylic
acid 16 (9.70 g, 43.7 mmol) and N,N0-dicylohexylcarbodiimide (DCC)
(4.95 g, 23.9 mmol) afforded 17, crystallized (EtOAc) to give colorless
crystals (8.86 g, 91% yield): mp 152e154 ꢀC; lit.42 mp 151e153 ꢀC.
(500.13 MHz, acetone-d6)
6CH2Ph), 7.24e7.32 (m, 30, PhH); 13C NMR (125.7 MHz, acetone-d6)
d 167.4 (C]O), 139.2, 129.1, 128.4, 128.3 (PhC), 73.9 (CH2Ph), 68.1
d 3.70 (s, 12H, 6CquatCH2O), 4.46 (s, 12H,
4.3.3. 5,5-Bis(benzyloxymethyl)-2-phenyl-1,3-dioxane (18). Mono-
O-benzylidinepentaerythritol60 (0.740 g, 3.30 mmol), NaH (60%)
(0.318 g, 7.95 mmol), and benzyl bromide (1.35 g, 7.89 mmol) were
dissolved in dry DMF (15 mL) at 0 ꢀC. The reaction flask was allowed
to warm to rt with stirring for 12 h. Water (3 mL) and CH2Cl2
(20 mL) were added and the resulting mixture was stirred for
10 min. The organic layer was collected, washed with water
(3ꢂ7 mL), dried (MgSO4), filtered, and concentrated to give crude
18 as a colorless solid. Purification using column chromatography
(hexanes/EtOAc; 5:1, Rf 0.45) gave 18 as a colorless crystalline solid
(1.15 g, 86% yield): mp 79 ꢀC; lit.51 mp 72 ꢀC; 1H NMR (500.13 MHz,
(CquatCH2O), 55.8 (Cquat.). HR ESI MS m/z calcd for C52H54NaO9
845.3660; found 845.3651.
4.4. Dendrimer synthesis
4.4.1. General procedure for formation of dendritic esters. To an
oven-dried round-bottomed flask equipped with a magnetic stir
bar under nitrogen atmosphere, the benzylidene or benzyl pro-
tected anhydride, the hydroxyl-terminated dendrimer or core, and
N,N-dimethyl-4-aminopyridine were dissolved in a 3:1 mixture of
CH2Cl2/pyridine (v/v). The reaction mixture was stirred at rt for
4e12 h and diluted with water (w3 mL) in pyridine (3 mL). Stirring
was continued overnight to quench the excess anhydride. The
mixture was diluted with CH2Cl2 (150 mL) and washed with
NaHCO3 (1 M, 30 mLꢂ3), 10% Na2CO3 (30 mLꢂ3), brine (30 mLꢂ2),
water (30 mL), dried (MgSO4), filtered, and concentrated. The crude
solid was then purified using precipitation out of hexanes/EtOAc or
column chromatography to give a colorless solid (92e97% yield).
The NaHCO3 layers were combined, acidified (pH¼5e6), and the
precipitated carboxylic acid by-product was recovered. However,
a different work up procedure was used for the synthesis of den-
drimer 30.
CDCl3)
d
3.46 (s, 2H, CH2eq), 3.99 (s, 2H, CH2ax), 4.03 (d, J¼11.5 Hz,
2H, H-4ax, H-6ax), 4.31 (d, J¼11.5 Hz, 2H, H-4eq, H-6eq), 4.58 (s, 2H,
OCH2Pheq), 4.70 (s, 2H, OCH2Phax), 5.54 (s, 1H, H-2), 7.38e7.50 (m,
13H, PhH), 7.57e7.59 (m, 2H, PhH); 13C NMR (125.7 MHz, CDCl3)
d
138.7, 138.4, 138.3, 129.0, 128.4, 128.33, 128.30, 127.7, 127.52,
127.46, 126.2 (PhC), 101.8 (C-2), 73.4 (OCH2Phax), 73.3 (OCH2Pheq),
70.3 (CH2ax), 70.2 (C-4, C-6), 68.9 (CH2eq), 39.0 (C-5). HR ESI MS m/z
calcd for C26H28NaO4 427.1880; found 427.1852.
4.3.4. 3-(Benzyloxy)-2,2-bis(benzyloxymethyl)propan-1-ol (19). To
a solution of benzylidene acetal (18) (2.00 g, 4.94 mmol) in anhy-
drous THF (10 mL) was added a 1 M solution of BH3.THF complex
(9.88 mL, 9.88 mmol) under nitrogen. Anhydrous CoCl2 (1.28 g,
9.88 mmol) was added in one portion and the reaction mixture was
stirred at rt for 20 min when TLC confirmed the disappearance of
the starting material. The reaction mixture was diluted using EtOAc
(40 mL) and filtered to remove undissolved CoCl2. The blue solution
was cooled to 0 ꢀC and aqueous NaBH4 solution was added drop-
wise with stirring until the blue color disappeared and there was
formation of a black precipitate. The mixture was filtered and the
organic layer was separated, washed with NaHCO3 (1 M, 10 mL),
water (10 mL), and dried (MgSO4). Concentration followed by col-
umn chromatography (hexanes/EtOAc; 3:1, Rf 0.39) gave the
product as a colorless syrup (1.83 g, 91% yield): 1H and 13C NMR
spectra similar to lit.52
4.4.2. General procedure for deprotection using hydrogenolysis. To
an oven-dried round-bottomed flask equipped with a magnetic
stir bar, the benzylidene or benzyl protected dendrimer was dis-
solved in a 1:2:1 mixture of CH2Cl2/MeOH/THF (v/v/v) and a cat-
alytic amount of Pd/C was added. The flask was evacuated and
back-filled with hydrogen three times. After stirring the mixture
overnight under H2 atmosphere, the catalyst was filtered off using
Celite and this Celite was washed with MeOH. The filtrate was
concentrated to dryness to afford the product as a colorless solid
(96e99% yield).
4.4.3. 1,4-Bis(2-((cis-5-methyl-r-2-phenyl-1,3-dioxan-5-yl)meth-
anoyloxy)ethyl)benzene (22). 1,4-Benzenediethanol (1, 0.630 g,
3.79 mmol), dry pyridine (11 mL), CH2Cl2 (33 mL), DMAP
(0.203 g, 1.66 mmol), and the anhydride 17 (3.88 g, 9.09 mmol)
were stirred at rt for 5 h under nitrogen. After work up and
purification as described above, the product was obtained as
colorless flakes (2.1 g, 97% yield): mp 138e140 ꢀC; 1H NMR
4.3.5. 3-(Benzyloxy)-2,2-bis(benzyloxymethyl)propanoic acid (20).
Alcohol 19 (11.3 g, 28.0 mmol) was dissolved in acetone (120 mL)
and the Jones reagent (0.56 M, 75 mL, 42 mmol) was added drop-
wise at 0 ꢀC with stirring over a 1 h period. The ice-water bath was
removed and stirring was continued for 8 h at rt. Acetone was re-
moved under vacuum and water (120 mL) was added. The aqueous
layer was extracted using diethyl ether (120 mLꢂ3). The combined
organic layers were washed with water (90 mLꢂ3), dried (MgSO4),
and concentrated. Purification using column chromatography
(hexanes/EtOAc; 3:1, Rf 0.27) gave the acid as a colorless solid
(8.68 g, 74% yield). Purification was also achieved using crystalli-
zation (hexanes/EtOAc) in 61% yield: mp 94e95 ꢀC; 1H NMR
(500.13 MHz, CDCl3)
d
0.95 (s, 6H, CH3), 2.95 (t, J¼7 Hz, 4H,
PhCH2), 3.62 (d, J¼11.5 Hz, 4H, H-4ax, H-6ax), 4.38 (t, J¼7 Hz, 4H,
CH2O), 4.63 (d, J¼11.5 Hz, 4H, H-4eq, H-6eq), 5.44 (s, 2H, H-2), 7.13
(s, 4H, PhH), 7.32e7.34 (m, 6H, PhH), 7.42e7.46 (m, 4H, PhH); 13C
NMR (125.7 MHz, CDCl3)
d 173.9 (C]O), 137.9, 136, 129.1, 129,
128.2, 126.2 (PhC), 101.8 (C-2), 73.5 (C-4, C-6), 65.5 (CH2O), 42.4
(Cquat), 34.7 (PhCH2), 17.9 (CH3). HR ESI MS m/z calcd for
C34H38NaO8 597.2459; found 597.2413.
(500.13 MHz, acetone-d6)
3CH2Ph), 7.25e7.34 (m, 15H, PhH), 10.89 (br, 1H, OH); 13C NMR
(125.7 MHz, acetone-d6) 173.9 (C]O), 139.5, 129.0, 128.14, 128.10
d 3.77 (s, 6H, 3CquatCH2 O), 4.53 (s, 6H,
d
4.4.4. 1,4-Bis-(2-(2,20-bis(hydroxymethyl)propanoyloxy)ethyl)ben-
zene (23). Compound 22 (1.22 g, 2.12 mmol) dissolved in dry
CH2Cl2 (15 mL), dry methanol (30 mL), and dry THF (15 mL) was
deprotected as in the general method to afford hydroxyl-termi-
nated 23 as a colorless crystalline solid (0.84 g, 99% yield): mp
(PhC), 73.7 (3CH2Ph), 68.8 (3CquatCH2O), 53.8 (Cquat). HR ESI MS m/z
calcd for C26H27O5 (MꢁH) 419.1864; found 419.1850.
4.3.6. 3-(Benzyloxy)-2,2-bis(benzyloxymethyl)propanoic anhydride
(21). Carboxylic acid (20) (23.9 g, 56.8 mmol) and DCC (6.44 g,
118e120 ꢀC; 1H NMR (500.13 MHz, methanol-d4)
d 1.09 (s, 6H,

9608
J. K. Twibanire et al. / Tetrahedron 66 (2010) 9602e9609
CH3), 2.92 (t, J¼7 Hz, 4H, PhCH2), 3.61 (AB q, DnAB¼22.3 Hz,
JAB¼10.5 Hz, 8H, CH2OH), 4.27 (t, J¼7 Hz, 4H, CH2O), 7.19 (s, 4H,
CH2CH2OC]O), 6.88 (s, 4H, PhH); 13C NMR (125.7 MHz, methanol-d4)
175.8 (4C]O), 174.4 (2C]O), 154.4, 116.9 (PhC), 67.6 (OCH2CH2O),
66.3 (4CH2OC]O), 65.7 (CH2OH), 65.0 (OCH2CH2O), 51.7 (4Cquat), 47.7
(2Cquat), 18.1 (2CH3), 17.2 (4CH3). HR ESI MS m/z calcd for C40H62NaO22
917.3625; found 917.3629.
d
PhH); 13C NMR (125.7 MHz, methanol-d4)
d
176.6 (C]O), 137.7,
130.1 (PhC), 66.3 (CH2O), 65.8 (CH2OH), 51.5 (Cquat), 35.6 (PhCH2),
17.3 (CH3). HR EIMS m/z calcd for C20H30NaO8 421.1833; found
421.1830.
4.4.9. 1,4-Bis-(2-(2,20,200-tris(benzyloxymethyl)ethanoyloxy)ethoxy)
benzene (28). Compound 28 was synthesized as described above in
the general dendritic ester procedure. The core moiety (3) (0.630 g,
3.18 mmol), dry pyridine (6 mL), CH2Cl2 (18 mL), DMAP (0.210 g,
1.72 mmol), and the anhydride 23 (6.15 g, 7.47 mmol) were stirred
at rt for 12 h under nitrogen. After work up and purification as
described above, the product was obtained as a colorless crystalline
solid (hexanes/EtOAc; 3:1; Rf 0.35) (2.99 g, 94%): mp 70 ꢀC; 1H NMR
4.4.5. 1,4-Bis(2-((cis-5-methyl-r-2-phenyl-1,3-dioxan-5-yl)meth-
anoyloxy)ethoxy)benzene (24). Compound 24 was synthesized as
described above in the general dendritic ester procedure. 1,4-Bis-
(2-hydroxyethoxy)benzene (3, 0.500 g, 2.52 mmol), dry pyridine
(6 mL), CH2Cl2 (18 mL), DMAP (0.135 g, 1.11 mmol), and the anhy-
dride 17 (2.58 g, 6.05 mmol) were stirred at rt for 4 h under ni-
trogen. After work up and purification as described above, the
product was obtained as a colorless solid (1.48 g, 97% yield): mp
(500.13 MHz, CDCl3)
d
3.71 (s, 12H, 6CquatCH2O), 4.01 (t, J¼5 Hz, 4H,
145 ꢀC; 1H NMR (500.13 MHz, CDCl3)
d
1.04 (s, 6H, CH3), 3.65 (d,
2PhOCH2), 4.42 (t, J¼5 Hz, 4H, 2CH2OC]O), 4.46 (s, 12H, 6CH2
J¼11.5 Hz, 4H, H-4ax, H-6ax), 4.16 (t, J¼5 Hz, 4H, PhOCH2O), 4.53 (t,
J¼5 Hz, 4H, OCH2CH2O), 4.68 (d, J¼11.5 Hz, 4H, H-4eq, H-6eq), 5.45
(s, 2H, H-2), 6.81 (s, 4H, PhH), 7.28e7.44 (m, 10H, PhH); 13C NMR
benzylic), 6.69 (s, 4H, PhH), 7.21e7.27 (m, 30H, PhH); 13C NMR
(125.7 MHz, CDCl3) d 172.6 (C]O),153.1,138.5, 128.4, 127.52,127.46,
115.8 (PhC), 73.3 (6CH2 benzylic), 68.0 (6CquatCO), 66.6 (2PhOC),
63.0 (2COC]O), 53.9 (Cquat). HR ESI MS m/z calcd for C62H66NaO12
1025.4446; found 1025.4429.
(125.7 MHz, CDCl3)
d 174.1 (C]O), 153.2, 138, 129.1, 128.3, 126.4,
116.1 (PhC), 102 (C-2), 73.7 (C-4, C-6), 66.9 (OCH2CH2O), 63.6
(OCH2CH2O), 42.7 (Cquat), 18.0 (CH3). HR ESI MS m/z calcd for
C34H38NaO10 629.2357; found 629.2352.
4.4.10. 1,4-Bis-(2-(2,20,200-tris(hydroxymethyl)ethanoyloxy)ethoxy)
benzene (29). Using the general procedure for deprotection de-
scribed above, 28 (1.74 g, 1.73 mmol), dissolved in dry CH2Cl2
(15 mL), dry MeOH (30 mL), and dry THF (15 mL) afforded 29 as
a colorless crystalline solid (0.77 g, 96% yield): mp 150e151 ꢀC; 1H
4.4.6. 1,4-Bis-(2-(2,20-bis(hydroxymethyl)propanoyloxy)ethoxy)ben-
zene (25). Using the general procedure for deprotection described
above, 24 (1.18 g, 1.95 mmol) dissolved in dry CH2Cl2 (15 mL), dry
methanol (30 mL) and dry THF (15 mL) afforded hydroxyl-termi-
nated 25 as a colorless solid (0.83 g, 99% yield): mp 155e156 ꢀC; 1H
NMR (500.13 MHz, methanol-d4)
J¼5 Hz, 4H, 2PhOCH2), 4.42 (t, J¼5 Hz, 4H, 2CH2OC]O), 6.90 (s, 4H,
PhH); 13C NMR (125.7 MHz, methanol-d4)
175.4 (C]O), 154.7,
d 3.77 (s, 12H, 6CH2O), 4.17 (t,
NMR (500.13 MHz, methanol-d4)
d
1.16 (s, 6H, CH3), 3.66 (AB q,
d
DnAB¼29.5 Hz, JAB¼11 Hz, 8H, CH2OH), 4.16 (t, J¼5 Hz, 4H, OCH2
116.5 (PhC), 71.1 (2PhOC), 61.8 (2COC]O), 61.5 (6COH), 57.1
(Cquat). HR ESI MS m/z calcd for C20H30NaO12 485.1629; found
485.1656.
-
CH2O), 4.40 (t, J¼5 Hz, 4H, OCH2CH2O), 6.89 (s, 4H, PhH); 13C NMR
(125.7 MHz, methanol-d4)
d 176.5 (C]O), 154.6, 116.9 (PhC), 67.9
(OCH2CH2O), 65.8 (CH2OH), 64.3 (OCH2CH2O), 51.6 (Cquat), 17.3
(CH3). HR ESI MS m/z calcd for C20H30NaO10 453.1731; found
453.1740.
4.4.11. 1,4-Bis-(2-(2,20,200-tris((cis-5-methyl-r-2-phenyl-1,3-dioxan-
5-yl)methanoyloxy-methyl)ethanoyloxy)ethoxy)benzene
(30). Compound 30 was synthesized as described above in the
general procedure for dendritic ester formation. Dendrimer 29
(0.550 g, 1.19 mmol), dry pyridine (4 mL), CH2Cl2 (12 mL), DMAP
(0.262 g, 2.14 mmol), and the anhydride 17 (3.80 g, 8.91 mmol)
were stirred at rt for 7 h under nitrogen. Water (4 mL) was added
and the ester product precipitated immediately. The product was
collected using suction filtration and was washed with methanol
(3ꢂ5 mL) to afford a colorless crystalline solid (1.95 g, 97% yield):
4.4.7. 1,4-(Bis-(2-(2,20-bis(cis-5-methyl-r-2-phenyl-1,3-dioxan-5-yl)
methanoyloxy-methyl)-propanoyloxy)ethoxy)benzene
(26). Compound 26 was synthesized as described above in the
general dendritic ester procedure. Compound 25 (0.800 g,
1.86 mmol), dry pyridine (5 mL), CH2Cl2 (15 mL), DMAP (0.200 g,
1.64 mmol), and the anhydride 17 (3.80 g, 8.91 mmol) were
stirred at rt for 10 h under nitrogen. After work up and purifi-
cation as described above, the product was obtained as a color-
less solid (2.13 g, 92% yield): mp 145 ꢀC; 1H NMR (500.13 MHz,
mp 183e185 ꢀC; 1H NMR (500.13 MHz, acetone-d6/DMSO-d6)
d
3.70
(d, J¼11.5 Hz, 12H, 6H-4ax, 6H-6ax), 3.93 (t, J¼4.5 Hz, 4H, 2PhOCH2),
CDCl3)
d
0.94 (s, 12H, 4CH3), 1.28 (s, 6H, 2CH3), 3.59 (d,
4.27 (t, J¼4.5 Hz, 4H, 2CH2OC]O), 4.44 (d, J¼11.5 Hz, 12H, 6H-4eq
,
J¼11.5 Hz, 8H, H-4ax, H-6ax), 3.89 (t, J¼5 Hz, 4H, OCH2CH2O),
4.27 (t, J¼5 Hz, 4H, OCH2CH2O), 4.41 (AB q, DnAB¼6 Hz,
JAB¼11 Hz, 8H, 4CH2OC]O), 4.58 (m, 8H, H-4eq, H-6eq), 5.42 (s,
4H, H-2), 6.69 (s, 4H, PhH), 7.28e7.42 (m, 20H, PhH); 13C NMR
6H-6eq), 4.47 (s, 12H, 2Cquat(CH2)3), 5.50 (s, 6H, H-2), 6.73 (s, 4H,
PhH), 7.30e7.38 (m, 30H, PhH); 13C NMR (125.7 MHz, acetone-d6/
DMSO-d6)
d 173.4 (6C]O), 170.5 (2C]O), 153.2, 138.9, 129.1, 128.4,
126.7,116.0 (PhC),101.5 (6C-2), 73.2 (6C-4, 6C-6), 66.4 (2PhOC), 64.4
(2CH2OC]O), 62.0 (2Cquat(CH2)3), 51.4 (2Cquat), 42.9 (6C-5), 17.5
(6CH3). HR ESI MS m/z calcd for C92H102Na2O30 866.3120; found
866. 3048.
(125.7 MHz, CDCl3)
d 173.4 (4C]O), 172.8 (2C]O), 153.0, 138,
129.0, 128.3, 126.3, 115.8 (PhC), 101.8 (C-2), 73.7, 73.6 (C-4, C-6),
66.3 (OCH2CH2O), 65.7 (4CH2O), 63.8 (OCH2CH2O), 47.0 (2Cquat),
42.7 (4Cquat), 17.9 (CH3). HR ESI MS m/z calcd for C68H78Na2O22
1269.4877; found 1269.4866.
4.4.12. 1,4-Bis-(2-(2,20,200-tris(2,20-bis(hydroxymethyl)propanoyloxy-
methyl)ethanoyloxy)-ethoxy)benzene (31). Using the general pro-
cedure for deprotection described above, 30 (1.50 g, 0.889 mmol),
dissolved in dry CH2Cl2 (30 mL), dry MeOH (15 mL), and dry THF
(15 mL) afforded 31 as a colorless crystalline solid (0.99 g, 96%
yield): mp 151e152 ꢀC; 1H NMR (500.13 MHz, DMSO-d6)
4.4.8. 1,4-Bis-(2-(2,20-bis(2,20-bis(hydroxymethyl)propanoyloxy-
methyl)propanoyloxy)-ethoxy)benzene (27). Using the general pro-
cedure for deprotection described above, 26 (1.95 g, 1.56 mmol)
dissolved in dry CH2Cl2 (15 mL), dry methanol (30 mL) and dry THF
(15 mL) afforded 27 as a colorless solid (1.36 g, 97% yield): mp
d
3.38e3.46 (m, 24H, 12CH2OH), 4.12 (t, J¼5 Hz, 4H, 2PhOCH2), 4.23
155e156 ꢀC; 1H NMR (500.13 MHz, methanol-d4)
d
1.12 (s, 12H, 4CH3),
(s, 12H, 2Cquat(CH2)3), 4.37 (t, J¼5 Hz, 4H, 2CH2OC]O), 4.67 (t,
1.28 (s, 6H, CH3), 3.62 (m, 16H, CH2OH), 4.17 (br m, 4H, PhOCH2CH2),
4.27 (AB q, DnAB¼19 Hz, JAB¼11 Hz, 8H, 4CH2OC]O), 4.43 (br m, 4H,
J¼5.5 Hz, 12H, 12OH), 6.87 (s, 4H, PhH); 13C NMR (125.7 MHz,
DMSO-d6)
d 174.0 (6C]O), 170.2 (2C]O), 152.5, 115.6 (PhC), 65.9

J. K. Twibanire et al. / Tetrahedron 66 (2010) 9602e9609
9609
24. Halligan, N. G.; Blaszczak, L. C. Org. Synth. 1990, 68, 104e108.
(2PhOCH2), 63.8 (2CH2OC]O), 63.6 (12CH2OH), 61.1 (2Cquat(CH2)
3), 50.4 (6CCH2OH), 50.3 (2Cquat), 16.7 (6CH3). HR ESI MS m/z calcd
for C50H78NaO30 1181.4470; found 1181.4470.
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Acknowledgements
We thank NSERC for support, Professor Jean Burnell for the loan
of his ozonolysis apparatus and NMR3 for NMR time.
Supplementary data
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