Synthesis of polyisoprene terpenoid dendrons and their applications in oligo(phenylene ethynylene)s as "shells"

Article abstract of DOI:10.1002/asia.201100480

The novel double-stage convergent synthesis of a new class of polyisoprene terpenoid (PIPTP) dendrons is described. PIPTP dendrons bear a highly branched aliphatic hydrocarbon skeleton and a hydrophilic hydroxy focal point functionality. These dendrons have the specific formula C _(5×2^G+1_-5)H_(5×2 ^G+2_-8)O, and each dendritic layer is constructed from an isoprene unit. The key branching steps involve a double alkyl-metal addition to an ester functionality, followed by deoxygenation of the resulting tertiary alcohol by triethylsilane and trifluoroacetic acid, then hydrogenation or hydrogenolysis. The dendrons were also attached to oligo(phenylene ethynylene)s (OPEs) so as to function as protective shells to allow fine tuning of the nanoscopic environment around the OPE moiety, and to exert precise control of the packing density and intermolecular interaction between the OPE cores. Fluorescence quantum yield data reveal that the OPE core is better encapsulated by the PIPTP dendrons than by Frechet dendrons.

Full text of DOI:10.1002/asia.201100480

DOI: 10.1002/asia.201100480
Synthesis of Polyisoprene Terpenoid Dendrons and their Applications in
Oligo(phenylene ethynylene)s as “Shells”
Wen-Yu Chai, Zi-Fa Shi, Peng An, Wei Wang, Lu-Feng Wang, and Xiao-Ping Cao*[a]
Abstract: The novel double-stage con-
vergent synthesis of a new class of
polyisoprene terpenoid (PIPTP) den-
drons is described. PIPTP dendrons
bear a highly branched aliphatic hydro-
carbon skeleton and a hydrophilic hy-
droxy focal point functionality. These
dendrons have the specific formula
volve a double alkyl-metal addition to
an ester functionality, followed by de-
oxygenation of the resulting tertiary al-
cohol by triethylsilane and trifluoroace-
tic acid, then hydrogenation or hydro-
genolysis. The dendrons were also at-
tached to oligo(phenylene ethynylene)s
(OPEs) so as to function as protective
shells to allow fine tuning of the nano-
scopic environment around the OPE
moiety, and to exert precise control of
the packing density and intermolecular
interaction between the OPE cores.
Fluorescence quantum yield data
reveal that the OPE core is better en-
capsulated by the PIPTP dendrons
than by Frꢁchet dendrons.
Keywords: dendrimers · hydrocar-
bons · oligomerization · polymers ·
terpenoids
G+1
G+2
C(5ꢀ2 -5)H(5ꢀ2 -8)O, and each den-
dritic layer is constructed from an iso-
prene unit. The key branching steps in-
Introduction
as the basic monomer. The aim of this study was concise—
efficient synthesis of these new dendrons with novel struc-
tures analogous to amphiphilic dendrimers, defined as poly-
isoprene terpenoid (PIPTP) dendrons.
Dendrimers are a class of highly branched macromolecules
with a highly ordered structure emanating from the core to
the surface, they have a large number of end groups and
unique properties.[1] Since Vçgtle first introduced dendrim-
ers in 1978[2] and Newkome[3] and Tomalia[4] proposed their
use as small molecule hosts in 1985, they have attracted the
attention of a number of researchers owing to their out-
standing and unique properties.[5] For example, they have
been employed as contrast agents in magnetic resonance
imaging,[6] drug delivery systems in medicine,[7] catalysis,[8]
molecular recognition,[5c] light harvesting,[9] and environmen-
tal applications.[10] Over the past decades, new types of den-
drimers with fascinating structures and properties have ap-
peared. Most notable are those derived from naturally oc-
curring starting materials such as nucleic acids, amino acids,
and carbohydrates. They are very appealing candidates for
many biomedical applications because of their perceived
biocompatibility owing to their derivation from natural in-
gredients. However, to the best of our knowledge, no bio-
dendrimers have been derived from one very important bio-
ingredient, namely the isoprene unit. Here we report our ef-
forts to construct a dendrimer composed of isoprene units
We begin by making two important points. First, amphi-
philic dendrimers, with both hydrophobic and hydrophilic
regions within one molecule, are becoming an important
class of dendrimers. Owing to their unusual architecture,
they possess many interesting and unique properties that
have attracted great interest for potential applications, such
as self-assembly,[11] gene transfection,[12] catalysis,[13] and
others.[14] Generally speaking, they are constructed either by
attaching hydrophilic chains to the surface of a hydrophobic
dendrimer,[15] or by fitting linear aliphatic hydrocarbon
chains to the surface of a hydrophilic core.[16] However, very
few studies have been concerned with the synthesis of den-
drimers based on a highly branched aliphatic hydrocarbon
skeleton, such as these PIPTP dendrons. To the best of our
knowledge, the earliest study was reported by Newkome
and co-workers, who prepared a G3 aliphatic dendron with
multiple hydrophilic hydroxy surfaces using a divergent
method.[17] Other examples are a series of G1–G3 aliphatic
dendrons with a polar hydrophilic carboxylic acid core that
were synthesized by Chow and co-workers by a convergent
route,[18] and a class of G1–G4 highly branched aliphatic hy-
drocarbon skeleton dendrons with a polar hydrophilic hy-
droxy functionality core that we synthesized through a
double-stage convergent method.[19]
[a] W.-Y. Chai, Dr. Z.-F. Shi, P. An, W. Wang, L.-F. Wang,
Prof. X.-P. Cao
State Key Laboratory of Applied Organic Chemistry and College of
Chemistry and Chemical Engineering
Lanzhou University, Lanzhou 730000 (P.R. China)
Fax : (+86)931-8915557
Second, it is likely that dendrimers will have structures
and properties analogous to those of terpenoid compounds
when the isoprene monomers connected head-to-tail act as
a hydrophobic part. Practically, the terpenoids,[20] which are
sometimes called isoprenoids, are an enormous and varied
class of naturally occurring organic chemicals similar to ter-
E-mail: caoxplzu@163.com
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201100480.
Chem. Asian J. 2012, 7, 143 – 155
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143

FULL PAPERS
penes,[21] which are derived
from five carbon isoprene
units[22] assembled and modi-
fied in thousands of ways.[23]
They are classified by the
number of isoprene units in
their skeleton, from one to
many. The prefix in the name
indicates the number of iso-
prene units needed to assem-
ble the molecule, such as hemi-
terpene, mono-, sesqui-, di-,
ses-, tri-, tetra-, and polyter-
penes. The terpenoids can be
regarded as modified terpenes
and similarly classified accord-
ing to the number of isoprene
units used. Deductively, the
PIPTP dendrons could also be
considered as dendrons with a
terpenoid skeleton interface
which is assorted with a corre-
sponding quantity of isoprene
units. Thus the G0-OH (1)
dendron is equated with hemi-
terpene analogs, and the G1-
OH (2) dendron is a sesquiter-
pene analog. Correspondingly,
the G3-OH (4) and G4-OH
(5) dendrons are treated as
polyterpenes. Probably the ear-
liest efforts in terpene chemis-
try were directed to develop-
G+
Figure 1. Structures of polyisoprene terpenoid (PIPTP) dendrons; the formula of PIPTP dendrons is C(5ꢀ2
1
G+2
À5)H(5ꢀ2 À8)O (G=0, 1, 2, 3, 4···); the number of polyisoprene monomers incorporated is N=2G+1À1 (G
represents the generation of the dendron).
ing a series of raw materials for a number of industrial
chemicals,[24] and a large number of terpene derivatives have
been discovered. For example, terpene alcohols,[25] terpene
phenols and ethers,[26] terpene acids,[27] terpene-derived
ureas,[28] terpene furoates,[29] and terpene-derived plasticiz-
ers[30] have been explored and intensively investigated. Nev-
ertheless, there have been very few reports in the literature
on dendrimers with terpene skeletons.
aliphatic chain was expected to possess even higher hydro-
phobicity and to be soluble in non-polar aliphatic hydrocar-
bons. Utilization of the focal point hydroxy functional group
also makes attachment of PIPTPs to other functional mole-
cules possible. The number of carbon and hydrogen atoms
in each generation of PIPTP dendrons can be calculated by
simple mathematical formulae. The number of carbon atoms
is given by NC =5ꢀ2G+1À5, and the number of hydrogen
atoms by NH =5ꢀ2G+2À8. Each dendritic layer is construct-
ed from an isoprene unit, and the number of polyisoprene
monomers incorporated N=2G+1À1, where G represents
the generation of the dendron.
After a series of exploratory investigations, we designed
and synthesized a series of new, wholly aliphatic chain
PIPTP dendrons 1–5 (Figure 1) with a hydroxy focal point,
by using a double-stage convergent method to overcome the
problem of steric inhibition in the preparation of the higher
generation G3 and G4 dendrons. The dendrons were subse-
quently attached to oligo(phenylene ethynylene) (OPE)
molecule wires as “shells”, thus allowing tailoring of the
nanoscopic environment surrounding OPE molecules and
acting as spacers for precise control of the packing density
and intermolecular interaction between the OPE cores. The
resulting materials were compared with OPEs wrapped with
Unlike other dendrimers, the PIPTP dendrons have a hy-
drocarbon skeleton that is constructed from only sp3-hybrid-
ized carbon systems. In that respect, PIPTP differs from
other oligoACHTUNGTRENNUNG
(arylene),[31] oligo(phenylenevinylene),[32] and oli-
go(phenylene ethynylene)s,[33] which are based on sp2- or sp-
hybridized carbon atoms. The PIPTP dendrons consist of
many hydrophobic isoprene monomers as branching chains,
and a hydrophilic hydroxy group as a focal point. The whole
Abstract in Chinese:
144
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Synthesis of Polyisoprene Terpenoid Dendrons
modified Frꢁchet dendrons, in relation to their spectroscopic
properties.[34]
bonds and removal of the benzyl group occurred simultane-
ously, and alcohol 12 was obtained in 85% overall yield
over two steps from 11. Soon afterwards alcohol 12 was con-
verted into the corresponding bromide 13 in the presence of
N-bromosuccinimide (NBS) and triphenylphosphine (PPh3)
in DCM at À788C to room temperature in the dark in 91%
yield.
Results and Discussion
In our synthetic route, the addition reaction of an ester or
diester with the alkyl-metal reagent was chosen as the criti-
cal process in the branching growth of the dendrons. This
approach greatly reduced the number of synthetic steps and
enhanced the overall yield of the target molecule. Generally
speaking, the G1-OH (2) and G2-OH (3) dendrons were
constructed by treating bromide 10 with ester 8 or diester
18, respectively, while G3-OH (4) and G4-OH (5) were
composed of bromide 13 or iodide 25 separately responding
to diester 18. All of these intermediates could be integrated
by esters 8 and 9 as the important materials. For the synthe-
sis of the G1-OH (2) and G2-OH (3) dendrons, ester 8 was
prepared in advance from commercially available 3-(benzy-
loxy)propan-1-ol (6) by Jones oxidation followed by esterifi-
cation with ethanol (cat. H2SO4) in 75% yield on a 100 g
scale (Scheme 1).[35] The analogous intermediate ester 9 was
obtained by a similar method in 77% yield from 4-(benzy-
loxy)butan-1-ol (7). Then, 1-bromo-4-methyl pentane (10)
was converted into the corresponding Grignard reagent in
ether and attacked ester 9 to afford tertiary alcohol 11 in
83% yield. The hydroxy group of 11 was removed by treat-
ment with triethylsilane (Et3SiH) and trifluoroacetic acid
(TFA) in dichloromethane (DCM) at room temperature, to
give a mixture of deoxygenation as well as isomeric hydroxy
elimination products. Fortunately, the mixture was convert-
ed without separation into alcohol 12 in the presence of
10% Pd/C under an atmosphere of hydrogen (1 atm) in
methanol. The hydrogenation of carbon–carbon double
For the synthesis of G3-OH (4) and G4-OH (5) dendrons,
two key branching intermediates, diester 18 and its homolog
19, which were used in the double-stage convergent growth
strategy, needed to be prepared beforehand (Scheme 2). The
Scheme 2. Synthesis of intermediates 18 and 19.
route included six steps to obtain the target molecules from
1,4-dibromobutane (14) as the starting material, using a sim-
ilar procedure and specific routes. First, single protection of
compound 14 using 4-methoxybenzyl alcohol (PMBOH) in
the presence of sodium hydroxide in benzene gave mono-
bromide 15 in 80% yield.[36] Bromide 15 was then converted
into the corresponding Grignard reagent and reacted with
ester 8 or 9 to afford the homologous tertiary alcohols 16 or
17 in 83% or 87% yield, respectively. Next, removal of the
two PMB protecting groups in 16 with ceric ammonium ni-
trate in acetonitrile (CH3CN)/H2O (v/v=1:1) without influ-
ence on the benzyl protecting group furnished the triol com-
pound. Subsequently, selective oxidation of the two primary
hydroxy groups produced the corresponding diacid using
Jones reagent in acetone with retention of the tertiary hy-
droxy group. Owing to the fact that there are two hydrophil-
ic carboxyl groups in the diacid, multiple extractions from
the aqueous phase was required to obtain the diacid.
Esterification of the crude diacid with ethanol (cat. H2SO4)
Scheme 1. Synthesis of intermediates 8, 9, and 13.
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145

X.-P. Cao et al.
FULL PAPERS
afforded a mixture of isomeric
unsaturated diesters owing to
the simultaneous elimination of
the tertiary hydroxy group. Fi-
nally, this mixture was hydro-
genated in the presence of 10%
Pd/C
and
triethylamine
(Et3N)[37] under an atmosphere
of hydrogen (1 atm) to produce
the desired product 18 in 41%
overall yield in four steps from
tertiary alcohol 16. Another
key branching intermediate 19
was prepared by a similar pro-
cedure in 43% overall yield in
four steps from compound 17.
Addition of Et3N only reduced
the carbon–carbon double bond
with the benzyl group retained,
which distinguished this proce-
dure from the previous proce-
dure described in Scheme 1.
With a series of important in-
termediates in hand after
a
number of preliminary synthe-
ses, we started to accomplish
the synthesis of G1-OH, G2-
OH, and G3-OH dendrons 2,[38]
3, and 4 (Scheme 3). Firstly, 1-
bromo-4-methyl pentane (10)
Scheme 3. Synthesis of dendrons 2 (G1-OH), 3 (G2-OH), and 4 (G3-OH).
was converted into the corre-
sponding Grignard reagent and
then attacked ester 8 to afford tertiary alcohol 20 in 83%
yield. The hydroxy group in 20 was treated with Et3SiH and
TFA in DCM at room temperature to give a mixture of de-
oxygenation as well as isomeric hydroxy elimination prod-
ucts.[39] Unfortunately, the result was not as we envisioned.
When the mixture was treated in the presence of 10% Pd/C
under an atmosphere of hydrogen (1 atm) following the pro-
cedure in Scheme 1, the G1-OH (2) dendron was obtained
in only 30% yield. After an extensive literature search, we
concluded that the allylic double bond resulted in the unex-
pected product. The tertiary hydroxy group in compound 20
facilitates elimination of the benzyloxy group more easily
than other substituents. Thus, the hydrogenolysis of the re-
sultant allyl benzyl ether led to formation of benzyl alcohol
and aliphatic hydrocarbon, which resulted in the low yield
of the G1-OH (2) dendron. We found a solution to the
problem after inspection of the literature[37] and experimen-
tation. First, hydrogenation of this mixture in the presence
of 10% Pd/C and Et3N under an atmosphere of hydrogen
(1 atm) reduced the carbon–carbon double bond whilst re-
taining the benzyl group. Then, hydrogenation of the result-
ing product without Et3N removed the benzyl group to give
the G1-OH (2) dendron in 81% overall yield in three steps
from tertiary alcohol 20. Thus, the first iterative synthetic
cycle was completed in four steps, and the G1-OH (2) den-
dron was obtained in 67% yield from bromide 10. Likewise,
the second synthetic cycle began with the same bromide 10,
which was first converted into the corresponding Grignard
reagent and then attacked ester 18 to afford compound 21
with two tertiary hydroxy groups in 82% yield. Soon after-
wards, treatment of 21 with Et3SiH and TFA in DCM at
room temperature gave a mixture of deoxygenation as well
as isomeric hydroxy elimination products, and hydrogena-
tion and hydrogenolysis carried out simultaneously in the
presence of 10% Pd/C under an atmosphere of hydrogen
(1 atm) afforded the G2-OH (3) dendron in 85% overall
yield in two steps. For the synthesis of the G3-OH (4) den-
dron, bromide 13 and diester 18 were used as the starting
materials by an accelerated double-stage convergent method
(Scheme 3). Bromide 13 reacted smoothly with magnesium
in ether to produce the corresponding Grignard reagent
with 1,2-dibromoethane. This was different from the previ-
ous procedure because of the lower activity of bromide 13
caused by the steric hindrance increment. It is noteworthy
that the formation of the Grignard reagent could only be in-
itiated when the concentration of bromide 13 was higher
than 1m. Under those conditions, reaction by addition of
ester 18 produced tertiary alcohol 22 in 81% yield based on
the recovered starting material. Subsequently, the tertiary
hydroxy groups in 22 were subjected to the same deoxyge-
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Synthesis of Polyisoprene Terpenoid Dendrons
nation protocol with Et3SiH and TFA followed by hydroge-
nation and hydrogenolysis to afford the G3-OH (4) dendron
in 82% overall yield in two steps.
Similarly, for the synthesis of the G4-OH (5) dendron, an
accelerated double-stage convergent method was used to
construct the carbon–carbon skeleton using iodide 25 and
diester 18 as starting materials. Iodide 25 was prepared from
alcohol 23 or diol 24 (Scheme 4). In the original route, bro-
With the requisite iodide 25 in place, according to our
original plan, the resulting corresponding Grignard reagent
that reacted with diester 18 should produce tertiary alcohol
26. However, because of the greater steric hindrance of
iodide 25, the Grignard reagent could not be obtained, as
the reaction could not be initiated despite many attempts.
We were pleased to find that unreacted iodide 25 and die-
ster 18 could be recovered quantitatively. On the basis of
our experience,[19] the Kagan–Molander samarium diiodide-
mediated coupling reaction was expected to be a good
method. Consequently, samarium instead of magnesium as
the alkyl-metal addition reagent was used to construct the
carbon–carbon skeleton of the G4-OH (5) dendron
(Scheme 5). First, iodide 25 (6.0 equiv) was treated with die-
ster 18 in the presence of SmI2 (12.0 equiv) and a catalytic
amount of NiI2 in tetrahydrofuran at room temperature, ac-
cording to the method reported by Namy and co-workers,[40]
to produce the desired diol 26 (51% yield) together with
the incomplete addition product alcohol 27 (10% yield).
Compound 27 could be converted into diol 26 in 60% yield
by further treatment with iodide 25 (3.0 equiv) in the pres-
ence of SmI2 (6.0 equiv) and NiI2 (cat.). Subsequently, the
tertiary hydroxy groups in 26 were deoxygenated cleanly
with Et3SiH and TFA at room temperature. Then, reduction
of the resulting carbon–carbon double bonds and removal of
the benzyl group were simultaneously carried out in the
presence of 10% Pd/C under an atmosphere of hydrogen
(1 atm) to produce the target G4-OH (5) dendron in 80%
overall yield in two steps.
Scheme 4. Synthesis of intermediate 25.
mide 13 reacted smoothly with magnesium in ether to pro-
duce the corresponding Grignard reagent, which then at-
tacked ester 9 to form tertiary alcohol 23 in 80% yield
based on the recovered starting material. Subsequently, the
smaller bromide 10 was selected to replace bromide 13; bro-
mide 10 reacted with diester 19 to afford tertiary alcohol 24
in 85% yield. Subsequently, two tertiary hydroxy groups in
24 were subjected to the deoxygenation protocol with
Et3SiH and TFA followed by hydrogenation, and treated
with imidazole, Ph3P, and iodine in DCM at room tempera-
ture to provide iodide 25 in 87% overall yield in three steps.
Similarly, alcohol 23 obtained by an incipient route was also
converted into iodide 25 in 81% overall yield in three steps.
Scheme 5. Synthesis of dendron 5 (G4-OH).
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1
All synthesized compounds were characterized by H and
13C NMR, DPET spectroscopy, mass spectrometry, and
exact mass measurement. 1H NMR spectra proved to be
very useful in the characterization of the various analogous
products. Hence, the chemical shift styles and conformable
integration information obtained from 1H NMR spectra
were very helpful for determining the generation of each
dendron, as well as the identity of the focal point functional
group of all compounds (Figure 2). After a series of compar-
expended in trying different sources of high-resolution mass
spectra to characterize the synthetic dendrons because of
their structural symmetry and very low polarity. However,
favorably, because of their inherent inertness, the raw mate-
rials could be recycled if reactions were unsuccessful or only
partially successful. This was the biggest advantage of the
synthetic route.
After completion of the synthesis of PIPTP dendrons G1-
OH to G4-OH (2–5), an interesting phenomenon was found
by reviewing previous work.[34] When the isoamyl group had
been selected as the “shell” of OPEs, the quantum yield of
28b (Figure 3 and Table 1) was the highest relative to the
corresponding five members with modified Frꢁchet den-
drons as “shells”[34] except for 28h. It was even higher than
for the OPEs with the modified G1 Frꢁchet dendron 28g as
a “shell”. A pleasant surprise was that the isoamyl group en-
wrapping the OPE structure as the “shell” was exactly the
skeleton of the G0-OH (1) dendron of the series of PIPTP
dendrons. Consequently, we speculated that the fluorescence
of OPE could be enhanced if the PIPTP dendrons were
used as “shells”. Thus it was thought worthwhile to investi-
gate the spectroscopic properties of OPEs with PIPTP den-
drons as “shells” 28c–28e to complete this project.
As OPEs 28b with the G0 dendron and 28 f–28h had
been synthesized in our previous work,[34] only G1-OH to
G3-OH dendrons 2, 3, and 4 were converted into corre-
sponding halides 29, 30, and 31, respectively, for the purpose
of attaching them to the two phenolic hydroxy groups of
OPEs. Furthermore, according to our experience of the un-
successful Grignard reaction in the synthesis of the G4-OH
(5) dendron, we anticipated that the steric hindrance of G1–
G3 halides would be increased progressively with increasing
generation of the dendrons. Hence, the larger G2-OH (3)
and G3-OH (4) dendrons were converted into the corre-
sponding iodide G2-I (30) and G3-I (31) dendrons to in-
crease their reactivity, and the smaller G1-OH (2) to the
bromide G1-Br (29) dendron (Scheme 6). Thus G1-OH (2)
was converted into the corresponding bromide G1-Br (29)
in the presence of NBS and PPh3 from À788C to room tem-
perature in the dark in DCM with 87% yield. In the other
cases, treatment of G2-OH (3) or G3-OH (4) with I2, Ph3P,
and imidazole in DCM at room temperature gave iodides
G2-I (30) and G3-I (31) in 91% or 90% yield, respectively.
The synthesis of OPEs proceeded according to Scheme 7.
First, the key intermediates 4-ethynyl-1-thioacetylbenzene
(35) and 1,4-diiodo-2,5-bis(methoxymethoxy)benzene (32)
were synthesized from 4-iodobenzenesulfonyl chloride and
hydroquinone over three steps in 74% overall yield, and
two steps in 60% overall yield, respectively, according to
the literature method[41] and our previous work.[34] Deprotec-
tion of the MOM groups of compound 32 by hydrochloric
acid gave another key intermediate diphenol 33 under
reflux conditions in methanol in 95% yield. Subsequently,
diphenol 33 was treated with different RBr or RI (29–31) in
the presence of potassium carbonate in N,N-dimethylforma-
mide (DMF) to afford compounds 34c–34e in satisfactory
yields (81–87%). It was noteworthy that the G1-Br (29) and
Figure 2. 1H NMR spectra of 2 (G1-OH), 3 (G2-OH), 4 (G3-OH), and 5
(G4-OH).
isons, it was found that the diagnostic integration ratio of
the surface methyl protons (d=0.86 ppm) to the a-methyl-
ene protons (d=3.66 ppm) adjacent to the oxygen atom was
3.0:1 (theoretical 3:1) for 1 (G0-OH), 6.0:1 (theoretical 6:1)
for 2 (G1-OH), 12.1:1 (theoretical 12:1) for 3 (G2-OH),
24.2:1 (theoretical 24:1) for 4 (G3-OH), and 48.5:1 (theoret-
ical 48:1) for 5 (G4-OH).
The synthesis of the new PIPTP dendrons with a wholly
aliphatic chain was thus accomplished for the first time. The
G4-OH (5) dendron was obtained in an overall yield of
10% from readily available starting materials in 15 steps.
Although the PIPTP dendrons look very simple, being com-
posed of carbon and hydrogen atoms and only one oxygen
atom, their synthesis was not easy, for the following four
main reasons. First, because the aliphatic hydrocarbon is in-
herently inert and the reactive functional group was wrap-
ped in its cavity, controllable growth duplication was more
difficult. Second, building carbon–carbon bonds between
sp3- and sp3-hybridized carbons is not easy owing to the
strong resistance of steric effects, which becomes more seri-
ous as the branched chain increases repetitively. Third, puri-
fying the synthetic dendrons was not simple because of their
low polarity owing to nonpolar surface sectors, especially in
higher generations. Finally, significant time and energy was
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Synthesis of Polyisoprene Terpenoid Dendrons
tion. Hence a range of different
temperatures were tested in
many trials. Compound 34e was
eventually obtained in 81%
yield when the temperature was
increased to 808C. Finally, com-
pounds 34c–34e were subjected
to palladium-catalyzed Sonoga-
shira cross-coupling with alkyne
35 at 508C under an atmos-
phere of hydrogen to provide
the desired compounds 28c–
28e in appropriate yield. It is
worth mentioning that when
the reaction was performed
under an inert atmosphere,
such as argon, it gave a very
low yield owing to the forma-
tion of the homocoupling prod-
uct of 35. For example, the
yield of compound 28c was
only 31% under an atmosphere
of argon, while the yield in-
creased to 72% under an at-
mosphere of hydrogen. This
was consistent with our obser-
vations in previous work.[34] In
addition, the steric hindrance
effect significantly lowered the
reaction rate with increasing di-
mension of dendrons, so that a
much longer reaction time was
required. In terms of molecular
1
characterization, H NMR spec-
tra proved to be very useful for
the various analogous products,
Figure 3. Structures of OPEs with dendrons as “shells”.
similar to the previously dis-
cussed comparison of G1-OH
Table 1. Spectroscopic properties of 28a–28h.
to G4-OH dendrons 2, 3, 4, and 5. The chemical shift styles
and conformable integration information obtained from
1H NMR spectra of compounds 34b–34e and OPEs 28b–
28e with PIPTP dendrons as “shells” were also very useful
for determining the generation of each dendron as well as
the functional group identity of all compounds (see the Sup-
porting Information).
To investigate the influence of dendrons attached to OPE
as “shells”, the synthesized molecules 28c–28e were first
characterized by ultraviolet and fluorescence spectroscopy;
the results are summarized in Table 1. The band positions of
UV/Vis spectra were almost the same for samples 28b, 28c–
28e, and 28 f–28h, which were red-shifted about 17 nm with
respect to that of 28a. The band positions in the fluores-
cence spectra of samples 28b–28e with PIPTP dendrons as
“shells” were also almost the same, and were red-shifted
about 20 nm with respect to those of 28a, and 7 nm with re-
spect to the modified Frꢁchet dendrons as “shells”. It was
easy to understand that these two kinds of dendrons played
OPEs
28a
28b
28c
28d
28e
28 f
28g
28h
labs[a] [nm]
lex[a] [nm]
lem[b] [nm]
F [%][c]
356
360
404
74.6
373
383
422
82.5
372
382
423
85.6
372
384
422
88.2
373
384
424
91.4
370
376
417
79.9
368
377
414
80.4
370
377
415
85.1
[a] Only the largest absorption maxima are listed. [b] Wavelength of
emission maximum when excited at the absorption maximum. [c] Quan-
tum yield using quinine sulfate (10 mm) as a standard and the samples
(10À6 m) in DCM.
G2-I (30) dendrons reacted smoothly at 508C but G3-I (31)
did not. The main reason was the iodide atom was enwrap-
ped by the branched chain of a larger dendron, thus making
the reaction more difficult. Fortunately, because of the in-
herent inertness and lack of reactive functionalities and ac-
tivities of the PIPTP dendrons, the substrates were recycled.
Thus, we considered that increasing the reaction tempera-
ture might be the best method to ensure a successful reac-
Chem. Asian J. 2012, 7, 143 – 155
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149

X.-P. Cao et al.
FULL PAPERS
in generation brought about an increase of quantum yield,
that is, 28b<28c<28d<28e and 28 f<28g<28h. All
members of these two series of dendrons as “shells” had a
much larger quantum yield than compound 28a. However,
each generation of PIPTP dendrons as “shells” gave slightly
higher quantum yields than the modified Frꢁchet aromatic
dendrons. The variation in the quantum yield can be attrib-
uted to the fact that the dendrimer “shells” prevent p–p
stacking from occurring between OPE cores. The OPEs
with PIPTP dendrons as “shells” (the 28b–28e series) con-
tained more hydrophobic aliphatic chain in each molecule.
Thus they have a higher solubility than 28a and the 28 f–28g
series modified by Frꢁchet dendrons as “shells” in most
common solvents. Moreover, sp3-hybridized carbons have a
greater freedom for rotation and have no p–p interaction
compared with the sp2-hybridized carbons in the “shells” of
compounds 28 f–28g. Theoretically, the free rotation of sp3-
hybridized carbons usually made a negative contribution to
the quantum yield, but in this special microenvironment, the
free rotation of sp3-hybridized carbons resulted in the pref-
erable encapsulation of OPEs with PIPTP dendrons. Thus,
the OPE core was more effectively encapsulated by all of
the PIPTP dendrons as “shells” than by the modified Frꢁ-
chet dendrons, and intermolecular interaction between the
OPE cores was more restricted. Hence the quantum yields
of 28b–28e were higher than their counterparts in the 28a
and 28 f–28g series. These preliminary studies suggested that
the OPEs with PIPTP dendrons as “shells” allowed fine
tuning of the nanoscopic environment around the OPE
moiety, and exerted precise control of the packing density
and intermolecular interaction between the cores. Further
studies are underway in our laboratory.
Scheme 6. Synthesis of intermediates 29 (G1-Br), 30 (G2-I), and 31 (G3-
I).
Conclusions
In conclusion, we have synthesized a new series of PIPTP
dendrons G1-OH to G4-OH (2, 3, 4, and 5), which possess a
highly branched aliphatic hydrocarbon skeleton and a hy-
drophilic hydroxy functional group. The double-stage con-
vergent synthesis of G3-OH and G4-OH was highly effi-
cient. This method allowed straightforward and rapid con-
struction of the dendritic species for investigation of their
structures and properties. The presence of the hydroxy or
halogen functional group in these dendrons enables their
conjugation to other functional moieties for modification of
their self-assembly properties. For example, the synthesis of
“core-shell” structured OPEs with PIPTP dendrons was ac-
complished, and the fluorescence quantum yields of these
OPEs showed an obvious dependence on the size of the
dendrimer shells. Moreover, each generation of PIPTP den-
drons as “shells” had a slightly higher quantum yield than
the modified Frꢁchet dendrons.
Scheme 7. Synthesis of OPEs with dendrons.
a role as a donor in the electronic structure. However, the
information in Table 1 also indicates that the band positions
of the UV/Vis and fluorescence spectra with the larger den-
drons were almost the same as with the smaller dendrons of
each type. This observation suggests that the incorporation
of various dendron shells did not bring about many changes
to the electronic structure of the conjugated OPE core.
However, an obvious difference of the fluorescence quan-
tum yield dependence on the various dendrimer shells can
be clearly seen. For the same type of dendron, an increase
150
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Chem. Asian J. 2012, 7, 143 – 155

Synthesis of Polyisoprene Terpenoid Dendrons
1-Bromo-8-methyl-4-(4-methylpentyl)nonane (13)
Experimental Section
A solution of PPh3 (7.56 g, 28.81 mmol) in dry CH2Cl2 (60 mL) was
added dropwise to a stirred suspension of NBS (5.13 g, 28.81 mmol) in
dry CH2Cl2 (60 mL) under an atmosphere of argon at À788C over 30 min
in the dark. Maintaining this temperature with stirring was continued
until all NBS disappeared (30 min), then a solution of alcohol 12 (5.82 g,
24.01 mmol) in dry CH2Cl2 (30 mL) was added dropwise at the same tem-
perature. The cooling bath was removed, and stirring was continued for
12 h at room temperature in the absence of light. The solvent was re-
moved in vacuo and the residue was purified by column chromatography
(petroleum ether) to provide bromide 13 (6.67 g, 91%) as a colorless oil.
1H NMR (400 MHz, CDCl3, 258C, TMS): d=3.39 (t, J=7.2 Hz, 2H),
1.80–1.87 (m, 2H), 1.48–1.58 (m, 2H), 1.25–1.40 (m, 2H), 1.19–1.23 (m,
9H), 1.12–1.17 (m, 4H), 0.86 ppm (d, J=6.8 Hz, 12H); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d=39.4 (CH2), 36.9 (CH), 34.4 (CH2),
33.8 (CH2), 32.2 (CH2), 30.2 (CH2), 27.9 (CH), 24.4 (CH2), 22.7 ppm
(CH3); HRMS (MALDI): m/z: calcd for C16H37BrN: 322.2104
[M+NH4]+; found: 322.2101.
All reactions that required anhydrous conditions were performed using
standard procedures under an atmosphere of argon. Commercially avail-
able reagents were used as received. The solvents were dried by distilla-
tion over the appropriate drying reagents. Petroleum ether was used for
column chromatography and had a b.p. range of 60–908C. Reactions
were monitored by TLC on silica-gel plates. Column chromatography
was generally performed through silica gel (200–300 mesh). Melting
points were determined by use of a Reichert Microscope apparatus and
are uncorrected. 1H, 13C NMR, and DEPT 135 were recorded on a Mer-
cury Plus-400 spectrometer or a Mercury Plus-300 spectrometer. The
chemical shifts (d) are reported in ppm and coupling constants (J) in Hz
and relative to TMS (d=0.00 ppm) for 1H NMR (s, d, t, m, and brs
denote singlet, doublet, triplet, multiplet, and broad singlet, respectively)
and chloroform (d=77.0 ppm) for the 13C NMR measurements. Mass
spectra (MALDI) and mass spectra (EI) were obtained on AXIMA-CFP
and TRACE DSQ mass spectrometers, respectively. High-resolution
mass spectral data (HRMS) were obtained on APEX II FT-MS (ESI) or
APEX-QE-FTMS (MALDI) mass spectrometers. UV/Vis spectra were
recorded on a T6 spectrophotometer by quartz cells with a pathlength of
1.0 cm. Fluorescence spectra were recorded on a Perkin–Elmer LS-55
spectrophotometer. Fluorescence quantum yields were determined by
using quinine sulfate (10 mm) as a standard and the samples (10À6 m) in
DCM.
1,9-Bis(4-methoxybenzyloxy)-5-[2-(benzyloxy)ethyl]nonan-5-ol (16)
According to the preceding procedure for the preparation of alcohol 11,
bromide 15 (30.00 g, 109.82 mmol), Mg turnings (3.16 g, 131.79 mmol),
and ester 8 (9.15 g, 43.92 mmol) afforded alcohol 16 (20.08 g, 83%) as a
colorless oil. 1H NMR (300 MHz, CDCl3, 258C, TMS): d=7.30–7.35 (m,
5H), 7.23 (d, J=6.6 Hz, 4H), 6.85 (d, J=6.6 Hz, 4H), 4.48 (s, 2H), 4.41
(s, 4H), 3.77 (s, 6H), 3.40–3.48 (m, 6H), 2.74 (brs, 1H), 1.62–1.79 (m,
2H), 1.51–1.60 (m, 4H), 1.23–1.49 ppm (m, 8H); 13C NMR (75 MHz,
CDCl3, 258C, TMS): d=159.0 (C), 137.7 (C), 130.6 (C), 129.2 (CH),
128.4 (CH), 127.7 (CH, overlapping signals), 113.6 (CH), 74.0 (C), 73.3
(CH2), 72.5 (CH2), 69.9 (CH2), 67.1 (CH2), 55.2 (CH3), 38.8 (CH2), 37.4
(CH2), 30.6 (CH2), 20.3 ppm (CH2); HRMS (ESI): m/z: calcd for
C34H47O6: 551.3367 [M+H]+; found: 551.3366.
6-[3-(Benzyloxy)propyl]-2,10-dimethylundecan-6-ol (11)
Mg turnings (1.74 g, 72.70 mmol) polished off with sandpaper, one small
flake of I2, and anhydrous ether (1 mL) were added to a dry flask pro-
tected by Ar. A solution of bromide 10 (10.00 g, 60.58 mmol) in anhy-
drous ether (80 mL) was added dropwise to this mixture at room temper-
ature, thus maintaining the micro-boiling state. The resultant mixture was
refluxed for 2 h, then a solution of 9 (5.39 g, 24.23 mmol) in anhydrous
ether (40 mL) was added dropwise and the mixture was refluxed for 5 h,
then treated with H2SO4 (2m, 60 mL) with ice-water bath cooling, and ex-
tracted with ether (3ꢀ80 mL). The combined organic phase was washed
with water, brine, dried (MgSO4), and concentrated in vacuo. The residue
was purified by column chromatography (petroleum ether/AcOEt=10:1)
1,9-Bis(4-methoxybenzyloxy)-5-[3-(benzyloxy)propyl]nonan-5-ol (17)
According to the preceding procedure for the preparation of alcohol 11,
bromide 15 (30.00 g, 109.82 mmol), Mg turnings (3.16 g, 131.79 mmol),
and ester 9 (9.76 g, 43.93 mmol) afforded alcohol 17 (21.58 g, 87%) as a
colorless oil. 1H NMR (400 MHz, CDCl3, 258C, TMS): d=7.30–7.35 (m,
5H), 7.24 (d, J=8.8 Hz, 4H), 6.85 (d, J=8.8 Hz, 4H), 4.49 (s, 2H), 4.41
(s, 4H), 3.77 (s, 6H), 3.41–3.48 (m, 6H), 1.75 (brs, 1H), 1.55–1.66 (m,
6H), 1.48–1.52 (m, 2H), 1.32–1.45 ppm (m, 8H); 13C NMR (100 MHz,
CDCl3, 258C, TMS): d=159.1 (C), 138.3 (C), 130.6 (C), 129.2 (CH),
128.3 (CH), 127.52 (CH), 127.45 (CH), 113.7 (CH), 73.7 (C), 72.8 (CH2),
72.5 (CH2), 70.9 (CH2), 69.9 (CH2), 55.2 (CH3), 38.9 (CH2), 36.0 (CH2),
30.2 (CH2), 23.8 (CH2), 20.2 ppm (CH2); HRMS (ESI): m/z: calcd for
C35H52NO6: 582.3789 [M+NH4]+; found: 582.3779.
to provide alcohol 11 (7.00 g, 83%) as
a
colorless oil. 1H NMR
(400 MHz, CDCl3, 258C, TMS): d=7.25–7.33 (m, 5H), 4.51 (s, 2H), 3.48
(t, J=6.4 Hz, 2H), 1.72 (s, 1H), 1.62–1.67 (m, 2H), 1.50–1.58 (m, 4H),
1.38–1.42 (m, 4H), 1.23–1.31 (m, 4H), 1.13–1.18 (m, 4H), 0.86 ppm (d,
J=6.8 Hz, 12H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=138.4
(C), 128.3 (CH), 127.54 (CH), 127.48 (CH), 73.9 (C), 72.9 (CH2), 70.9
(CH2), 39.6 (CH2), 39.5 (CH2), 36.1 (CH2), 27.9 (CH), 23.9 (CH2), 22.6
(CH3), 21.3 ppm (CH2); HRMS (ESI): m/z: calcd for C23H40O2Na:
371.2921 [M+Na]+; found: 371.2920.
Diethyl 5-[2-(benzyloxy)ethyl]nonanedioate (18)
8-Methyl-4-(4-methylpentyl)nonan-1-ol (12)
Ammonium ceric nitrate (CAN) (39.82 g, 72.63 mmol) was added in
batches to a stirred solution of alcohol 16 (10.00 g, 18.16 mmol) in a mix-
ture of solvent (CH3CN/H2O=2:1, 300 mL) in an ice-bath. After the re-
action mixture was stirred for 6 h at this temperature, Na2SO3 (2.06 g,
16.34 mmol) and saturated NaHCO3 (50 mL) were added. The reaction
mixture was extracted with CHCl3 (3ꢀ60 mL), and the combined organic
phase was washed with water, brine, dried MgSO4, and concentrated in
vacuo. The residue was purified by column chromatography (AcOEt/
MeOH=50:1) to provide the triol as a colorless oil. According to the
preceding procedure for the preparation of ester 8, the triol was trans-
formed into an unsaturated diester, which was added to the mixture of
Et3N (2 mL) and 10% Pd/C (0.10 g) in MeOH. After the H2-degassed re-
action mixture was stirred under an atmosphere of hydrogen (1 atm) for
6 h at room temperature, the mixture was filtered through a plug (silica
gel, AcOEt). The filtrate was concentrated in vacuo and the residue was
purified by column chromatography (petroleum ether/AcOEt=10:1) to
provide diester 18 (3.06 g, 41%) as a colorless oil. 1H NMR (300 MHz,
CDCl3, 258C, TMS): d=7.26–7.34 (m, 5H), 4.48 (s, 2H), 4.11 (q, J=7.5,
4.5 Hz, 4H), 3.48 (t, J=7.2 Hz, 2H), 2.26 (t, J=7.8 Hz, 4H), 1.50–1.65
(m, 7H), 1.21–1.33 ppm (m, 10H); 13C NMR (75 MHz, CDCl3, 258C,
Et3SiH (5.03 mL, 31.56 mmol) and TFA (10.62 mL, 143.45 mmol) were
added to a stirred solution of alcohol 11 (10.00 g, 28.69 mmol) in CH2Cl2
(100 mL). After the reaction mixture was stirred for 12 h at room temper-
ature, Na2CO3 (20 g) was added until no bubbles emerged, then the mix-
ture was filtered through a plug (silica gel, CH2Cl2). The filtrate was con-
centrated in vacuo and purified by column chromatography (petroleum
ether/AcOEt=20:1) to provide the hydroxy eliminated product as a col-
orless oil. This was dissolved in a solution of MeOH and 10% Pd/C
(0.10 g) was added. After the H2-degassed reaction mixture was stirred
under an atmosphere of hydrogen (1 atm) for 6 h at room temperature,
the mixture was filtered through a plug (silica gel, AcOEt). The filtrate
was concentrated in vacuo. The residue was purified by column chroma-
tography (petroleum ether/AcOEt=10:1) to provide alcohol 12 (5.91 g,
85%) as a colorless oil. 1H NMR (400 MHz, CDCl3, 258C, TMS): d=
3.61 (t, J=6.8 Hz, 2H), 1.47–1.57 (m, 4H), 1.22–1.29 (m, 11H), 1.10–1.15
(m, 4H), 0.85 ppm (d, J=6.8 Hz, 12H); 13C NMR (100 MHz, CDCl3,
258C, TMS): d=63.5 (CH2), 39.5 (CH2), 37.3 (CH), 33.9 (CH2), 30.0
(CH2), 29.6 (CH2), 27.9 (CH), 24.4 (CH2), 22.6 ppm (CH3); HRMS (ESI):
m/z: calcd for C16H38ON: 260.2948 [M+NH4]+; found: 260.2953.
Chem. Asian J. 2012, 7, 143 – 155
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151

X.-P. Cao et al.
FULL PAPERS
TMS): d=173.5 (C), 138.5 (C), 128.2 (CH), 127.5 (CH), 127.4 (CH), 72.8
(CH2), 68.3 (CH2), 60.1 (CH2), 34.5 (CH2), 34.1 (CH), 33.3 (CH2), 32.8
(CH2), 21.8 (CH2), 14.1 ppm (CH3); HRMS (ESI): m/z: calcd for
C22H38O5N: 396.2744 [M+NH4]+; found: 396.2747.
11-Methyl-7-(4-methylpentyl)-3-[8-methyl-4-(4-
methylpentyl)nonyl]dodecan-1-ol (3)
Similar to the preceding procedure for the preparation of alcohol 12, diol
21 (1.00 g, 1.58 mmol) was treated with Et3SiH (0.56 mL, 3.49 mmol) and
TFA (1.17 mL, 15.85 mmol) in CH2Cl2 (10 mL), then hydrogenated in a
mixture of solvent (AcOEt/MeOH=7:1, 8 mL) to provide G2-OH (3)
Diethyl 5-[3-(benzyloxy)propyl]nonanedioate (19)
According to the preceding procedure for the preparation of diester 18,
alcohol 17 (10.00 g, 17.71 mmol) afforded diester 19 (2.99 g, 43%) as a
colorless oil. 1H NMR (300 MHz, CDCl3, 258C, TMS): d=7.27–7.35 (m,
5H), 4.50 (s, 2H), 4.11 (q, J=7.2, 6.9 Hz, 4H), 3.44 (t, J=7.2 Hz, 2H),
2.27 (t, J=7.8 Hz, 4H), 1.54–1.64 (m, 6H), 1.23–1.35 ppm (m, 13H);
13C NMR (75 MHz, CDCl3, 258C, TMS): d=173.7 (C), 138.5 (C), 128.3
(CH), 127.6 (CH), 127.5 (CH), 72.9 (CH2), 70.7 (CH2), 60.2 (CH2), 36.8
(CH), 34.6 (CH2), 32.7 (CH2), 29.5 (CH2), 26.7 (CH2), 22.0 (CH2),
14.2 ppm (CH3); HRMS (ESI): m/z: calcd for C23H37O5: 393.2636
[M+H]+; found: 393.2633.
1
(0.69 g, 85%) as a colorless oil. H NMR (300 MHz, CDCl3, 258C, TMS):
d=3.66 (t, J=6.9 Hz, 2H), 1.44–1.57 (m, 6H), 1.06–1.22 (m, 40H),
0.85 ppm (d, J=6.6 Hz, 24H); 13C NMR (75 MHz, CDCl3, 258C, TMS):
d=61.3 (CH2), 39.5 (CH2), 37.4 (CH), 37.1 (CH2), 34.3 (CH), 34.2 (CH2),
34.1 (CH2), 33.9 (CH2), 27.9 (CH), 24.4 (CH2), 23.6 (CH2), 22.7 ppm
(CH3); HRMS (ESI): m/z: calcd for C35H76ON: 526.5921 [M+NH4]+;
found: 526.5915.
14-[2-(Benzyloxy)ethyl]-2,26-dimethyl-6,22-bis(4-methylpentyl)-10,18-
bis[8-methyl-4-(4-methylpentyl)nonyl]heptacosane-10,18-diol (22)
6-[2-(Benzyloxy)ethyl]-2,10-dimethylundecan-6-ol (20)
According to the preceding procedure for the preparation of alcohol 11,
bromide 13 (2.00 g, 6.55 mmol), Mg turnings (0.19 g, 7.86 mmol), and die-
ster 18 (0.99 g, 2.62 mmol) (triggered with 1,2-dibromoethane) provided
diol 22 (2.53 g, 81%) as a colorless oil. 1H NMR (300 MHz, CDCl3,
258C, TMS): d=7.24–7.34 (m, 5H), 4.49 (s, 2H), 3.49 (t, J=6.6 Hz, 2H),
1.46–1.63 (m, 15H), 1.11–1.37 (m, 84H), 0.86 ppm (d, J=6.3 Hz, 48H);
13C NMR (75 MHz, CDCl3, 258C, TMS): d=138.7 (C), 128.3 (CH), 127.6
(CH), 127.4 (CH), 76.6 (CH2), 74.5 (C), 72.9 (CH2), 68.7 (CH2), 39.9
(CH2), 39.7 (CH2), 39.5 (CH2), 37.4 (CH), 34.8 (CH), 34.4 (CH2), 34.0
(CH2), 33.9 (CH2), 30.5 (CH2), 27.9 (CH), 24.4 (CH2), 22.7 (CH3), 20.7
(CH2), 20.5 ppm (CH2); HRMS (MALDI): m/z: calcd for C82H158O3Na:
1214.2103 [M+Na]+; found: 1214.2100.
According to the preceding procedure for the preparation of alcohol 11,
bromide 10 (10.00 g, 60.58 mmol), Mg turnings (1.74 g, 72.70 mmol), and
ester 8 (5.05 g, 24.23 mmol) afforded alcohol 20 (6.73 g, 83%) as a color-
less oil. 1H NMR (300 MHz, CDCl3, 258C, TMS): d=7.23–7.38 (m, 5H),
4.52 (s, 2H), 3.66 (t, J=5.4 Hz, 2H), 3.03 (s, 1H), 1.76–1.79 (m, 2H),
1.13–1.60 (m, 14H), 0.85 ppm (d, J=6.3 Hz, 12H); 13C NMR (75 MHz,
CDCl3, 258C, TMS): d=137.7 (C), 128.3 (CH), 127.6 (CH, overlapping
signals), 74.0 (C), 73.3 (CH2), 67.1 (CH2), 39.5 (CH2), 39.2 (CH2), 37.6
(CH2), 27.8 (CH), 22.6 (CH3), 21.3 ppm (CH2); HRMS (ESI): m/z: calcd
for C44H77O4: 669.5816 [2M+H]+; found: 669.5806.
7-Methyl-3-(4-methylpentyl)octan-1-ol (2)
15-Methyl-11-(4-methylpentyl)-7-[8-methyl-4-(4-methylpentyl)nonyl]-3-
{12-methyl-8-(4-methylpentyl)-4-[8-methyl-4-(4-
methylpentyl)nonyl]tridecyl} hexadecan-1-ol (4)
Et3SiH (2.62 mL, 16.44 mmol) and TFA (5.53 mL, 74.73 mmol) were
added to a stirred solution of alcohol 20 (5.00 g, 14.95 mmol) in CH2Cl2
(50 mL). After the reaction mixture was stirred for 12 h at room temper-
ature, Na2CO3 (10 g) was added until no bubbles emerged, then the mix-
ture was filtered through a plug (silica gel, CH2Cl2). The filtrate was con-
centrated in vacuo and purified by column chromatography (petroleum
ether/AcOEt=20:1) to provide the hydroxy eliminated product as a col-
orless oil. This was dissolved in a solution of MeOH with addition of
Et3N (2 mL) and 10% Pd/C (0.10 g). After the H2-degassed reaction mix-
ture was stirred under an atmosphere of hydrogen (1 atm) for 6 h at
room temperature, the mixture was filtered through a plug (silica gel,
AcOEt). The filtrate was concentrated in vacuo. The residue was hydro-
genated without Et3N and purified by column chromatography (petrole-
um ether/AcOEt=10:1) to provide G1-OH (2) (2.77 g, 81%) as a color-
less oil. 1H NMR (300 MHz, CDCl3, 258C, TMS): d=3.66 (t, J=7.2 Hz,
2H), 1.50–1.57 (m, 4H), 1.40–1.48 (m, 2H), 1.20–1.36 (m, 8H), 1.10–1.17
(m, 4H), 0.86 ppm (d, J=5.1 Hz, 12H); 13C NMR (75 MHz, CDCl3,
258C, TMS): d=61.3 (CH2), 39.4 (CH2), 37.0 (CH2), 34.3 (CH), 34.0
(CH2), 27.9 (CH), 24.3 (CH2), 22.6 ppm (CH3); HRMS (ESI): m/z: calcd
for C15H36ON: 246.2791 [M+NH4]+; found: 246.2793.
Similar to the preceding procedure for the preparation of alcohol 12, diol
21 (1.00 g, 0.84 mmol) was treated with Et3SiH (0.29 mL, 1.85 mmol) and
TFA (0.62 mL, 8.39 mmol) in CH2Cl2 (10 mL), then hydrogenated in a
mixture of solvent (AcOEt/MeOH=7:1, 8 mL) to provide G3-OH (4)
1
(0.74 g, 82%) as a colorless oil. H NMR (400 MHz, CDCl3, 258C, TMS):
d=3.67 (t, J=6.8 Hz, 2H), 1.43–1.58 (m, 8H), 1.11–1.23 (m, 94H),
0.86 ppm (d, J=6.8 Hz, 48H); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d=61.4 (CH2), 39.5 (CH2), 37.4 (CH, overlapping signals), 37.0 (CH2),
34.42 (CH), 34.36 (CH2), 34.3 (CH2), 34.2 (CH2), 34.1 (CH2), 28.0 (CH),
24.4 (CH2, overlapping signals), 23.7 (CH2), 22.7 ppm (CH3); HRMS
(ESI): m/z: calcd for C75H153O: 1070.1916 [M+H]+; found: 1070.1933.
1-Iodo-12-methyl-8-(4-methylpentyl)-4-[8-methyl-4-(4-methylpentyl)nonyl]
tridecane (25)
According to the preceding procedure for the preparation of alcohol 12
or G2-OH (3), alcohol 23 or diol 24 afforded the same alcohol as a color-
less oil. 1H NMR (400 MHz, CDCl3, 258C, TMS): d=3.62 (t, J=6.8 Hz,
2H), 1.50–1.56 (m, 9H), 1.11–1.31 (m, 38H), 0.86 ppm (d, J=6.4 Hz,
24H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=63.6 (CH2), 39.5
(CH2), 37.4 (CH), 37.2 (CH), 34.1 (CH2), 34.0 (CH2), 33.9 (CH2), 30.0
(CH2), 29.6 (CH2), 27.9 (CH), 24.4 (CH2), 23.7 (CH2), 22.7 ppm (CH3);
HRMS (ESI): m/z: calcd for C36H74ONa: 545.5632 [M+Na]+; found:
545.5642. Then, I2 (0.73 g, 2.87 mmol) was added to a stirred mixture of
imidazole (0.20 g, 2.87 mmol) and PPh3 (0.75 g, 2.87 mmol) in CH2Cl2
(20 mL) at room temperature. After the solution was stirred for 1 h, a so-
lution of this alcohol (1.00 g, 1.91 mmol) in CH2Cl2 (10 mL) was added
dropwise. The reaction mixture was stirred for 6 h, then washed with
Na2S2O3 (10% aq.) and brine. The combined organic phase was dried
(MgSO4) and concentrated in vacuo. The residue was purified by column
chromatography (petroleum ether) to provide iodide 25 (1.14 g, 94%) as
a colorless oil. 1H NMR (400 MHz, CDCl3, 258C, TMS): d=3.17 (t, J=
7.2 Hz, 2H), 1.78–1.82 (m, 2H), 1.48–1.58 (m, 4H), 1.11–1.36 (m, 41H),
0.86 ppm (t, J=6.4 Hz, 24H); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d=39.5 (CH2), 37.4 (CH), 36.7 (CH), 34.5 (CH2), 34.1 (CH2), 34.0 (CH2),
33.9 (CH2), 30.9 (CH2), 28.0 (CH), 24.4 (CH2), 23.6 (CH2), 22.7 (CH3),
10-[2-(Benzyloxy)ethyl]-2,18-dimethyl-6,14-bis(4-
methylpentyl)nonadecane-6,14-diol (21)
According to the preceding procedure for the preparation of alcohol 11,
bromide 10 (2.00 g, 12.12 mmol), Mg turnings (0.35 g, 14.54 mmol), and
diester 18 (1.83 g, 4.85 mmol) provided diol 21 (2.51 g, 82%) as a color-
less oil. 1H NMR (300 MHz, CDCl3, 258C, TMS): d=7.24–7.32 (m, 5H),
4.48 (s, 2H), 3.48 (t, J=6.6 Hz, 2H), 1.69 (brs, 2H), 1.48–1.59 (m, 8H),
1.15–1.35 (m, 35H), 0.87 ppm (d, J=6.6 Hz, 24H); 13C NMR (75 MHz,
CDCl3, 258C, TMS): d=138.5 (C), 128.1 (CH), 127.4 (CH), 127.3 (CH),
74.2 (C), 72.7 (CH2), 68.5 (CH2), 39.6 (CH2), 39.5 (CH2), 39.2 (CH2), 34.2
(CH), 34.1 (CH2), 33.5 (CH2), 27.7 (CH), 22.5 (CH3), 21.1 (CH2),
20.0 ppm (CH2); HRMS (ESI): m/z: calcd for C42H78O3Na: 653.5843
[M+Na]+; found: 653.5846.
152
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ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2012, 7, 143 – 155

Synthesis of Polyisoprene Terpenoid Dendrons
7.8 ppm (CH2); HRMS (MALDI): m/z: calcd for C36H77IN: 650.5095
[M+NH4]+; found: 650.5097.
d=39.3 (CH2), 37.3 (CH2), 36.5 (CH), 33.4 (CH2), 32.2 (CH2), 27.9 (CH),
24.2 (CH2), 22.6 ppm (CH3); HRMS (MALDI): m/z: calcd for
C15H35BrN: 308.1947 [M+NH4]+; found: 308.1949.
18-[2-(Benzyloxy)ethyl]-2,34-dimethyl-6,30-bis(4-methylpentyl)-10,26-
bis[8-methyl-4-(4-methylpentyl)nonyl]-14,22-bis{12-methyl-8-(4-
methylpentyl)-4-[8-methyl-4-(4-methylpentyl)nonyl]tridecyl}-
pentatriacontane-14,22-diol (26) and Ethyl 5-[2-(benzyloxy)ethyl]-9-
hydroxy-21-methyl-17-(4-methylpentyl)-13-[8-methyl-4-(4-
methylpentyl)nonyl]-9-{12-methyl-8-(4-methylpentyl)-4-[8-methyl-4-(4-
methylpentyl)nonyl]tridecyl}docosanoate (27)
1-Iodo-11-methyl-7-(4-methylpentyl)-3-[8-methyl-4-(4-methylpentyl)nonyl]
dodecane (30)
Similar to the preceding procedure for the preparation of iodide 25, G2-
OH (3) (0.50 g, 0.98 mmol), I2 (0.38 g, 1.48 mmol), imidazole (0.10 g,
1.47 mmol), and PPh3 (0.39 g, 1.47 mmol) provided iodide 30 (0.55 g,
91%) as a colorless oil. 1H NMR (400 MHz, CDCl3, 258C, TMS): d=
3.20 (t, J=7.6 Hz, 2H), 1.79–1.84 (m, 2H), 1.48–1.58 (m, 7H), 1.12–1.26
(m, 36H), 0.86 ppm (t, J=6.4 Hz, 24H); 13C NMR (100 MHz, CDCl3,
258C, TMS): d=39.5 (CH2), 38.6 (CH), 37.4 (CH), 34.1 (CH2), 34.0
(CH2, overlapping signals), 33.4 (CH2), 28.0 (CH), 24.4 (CH2), 23.5
(CH2), 22.7 (CH3), 7.8 ppm (CH2); HRMS (MALDI): m/z: calcd for
C35H75IN: 636.4939 [M+NH4]+; found: 636.4941.
NiI2 (0.01 g, 0.03 mmol) was added to
3.16 mmol) in THF (31.6 mL) under argon at room temperature. After
the solution was stirred for 1 h, solution of iodide 25 (1.00 g,
a solution of SmI2 (1.28 g,
a
1.58 mmol) and diester 18 (0.10 g, 0.26 mmol) in THF (10 mL) was added
dropwise within 20 min. The mixture was then stirred for an additional
period of 2 h, then diluted with ether (20 mL), quenched with HCl (1m),
and stirred for 15 min to obtain a clear solution, which was extracted
with ether (3ꢀ20 mL). The combined organic phase was washed with
brine, aqueous sodium thiosulfate and brine again, dried (MgSO4), and
concentrated in vacuo. The residue was purified by column chromatogra-
phy (petroleum ether/AcOEt=100:1) to provide diol 26 (0.31 g, 51%)
and ester 27 (35 mg, 10%) as a colorless oil. For the diol 26: 1H NMR
(400 MHz, CDCl3, 258C, TMS): d=7.26–7.34 (m, 5H), 3.49 (t, J=6.8 Hz,
2H), 1.48–1.60 (m, 19H), 1.11–1.37 (m, 194H), 0.86 ppm (d, J=6.4 Hz,
96H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=138.6 (C), 128.3
(CH), 127.6 (CH), 127.5 (CH), 74.4 (C), 72.9 (CH2), 68.7 (CH2), 39.9
(CH2), 39.7 (CH2), 39.5 (CH2, overlapping signals), 37.5 (CH, overlapping
signals), 34.6 (CH), 34.3 (CH2), 34.1 (CH2), 33.92 (CH2), 33.91 (CH2),
28.0 (CH), 24.4 (CH2), 20.4 (CH2), 23.7 (CH2), 22.7 (CH3), 20.7 ppm
(CH2); HRMS (MALDI): m/z: calcd for C162H318O3Na: 2335.4623
[M+Na]+; found: 2335.4546. For the ester 27: 1H NMR (400 MHz,
CDCl3, 258C, TMS): d=7.33–7.34 (m, 5H), 4.49 (s, 2H), 4.12 (q, J=7.2,
6.8 Hz, 2H), 3.49 (t, J=6.8 Hz, 2H), 2.26 (t, J=7.6 Hz, 2H), 1.49–1.63
(m, 13H), 1.37–1.39 (m, 5H), 1.11–1.27 (m, 97H), 0.86 ppm (t, J=6.4 Hz,
48H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=173.7 (C), 138.6 (C),
128.3 (CH), 127.6 (CH), 127.5 (CH), 74.4 (C), 72.9 (CH2), 68.6 (CH2),
60.2 (CH2), 39.8 (CH2), 39.5 (CH2, overlapping signals), 37.5 (CH), 37.4
(CH), 34.62 (CH2), 34.55 (CH), 34.4 (CH2), 34.2 (CH2), 34.0 (CH2), 33.91
(CH2), 33.90 (CH2), 33.5 (CH2), 33.1 (CH2), 27.9 (CH), 24.4 (CH2), 23.7
(CH2), 22.7 (CH3), 22.0 (CH2), 20.7 (CH2), 20.3 (CH2), 14.3 ppm (CH3);
HRMS (MALDI): m/z: calcd for C92H176O4Na: 1368.3461 [M+Na]+;
found: 1368.3435. Diol 26 from ester 27: According to the preceding pro-
cedure for the preparation of diol 26, ester 27 (25 mg, 0.018 mmol) and
iodide 25 (35 mg, 0.055 mmol) were treated with SmI2 (45 mg,
0.11 mmol) and NiI2 (1 mg, 0.003 mmol) afforded diol 26 (26 mg, 60%)
as a colorless oil.
1-Iodo-15-methyl-11-(4-methylpentyl)-7-[8-methyl-4-(4-
methylpentyl)nonyl]-3-{12-methyl-8-(4-methylpentyl)-4-[8-methyl-4-(4-
methylpentyl)nonyl]tridecyl} hexadecan (31)
Similar to the preceding procedure for the preparation of iodide 25, G3-
OH (4) (0.30 g, 0.28 mmol), I2 (0.11 g, 0.42 mmol), imidazole (0.03 g,
0.42 mmol), and PPh3 (0.11 g, 0.42 mmol) provided iodide 31 (0.30 g,
90%) as a colorless oil. 1H NMR (400 MHz, CDCl3, 258C, TMS): d=
3.19 (t, J=7.2 Hz, 2H), 1.79–1.84 (m, 2H), 1.43–1.58 (m, 8H), 1.12–1.26
(m, 91H), 0.87 ppm (t, J=6.4 Hz, 48H); 13C NMR (100 MHz, CDCl3,
258C, TMS): d=39.5 (CH2), 38.7 (CH), 37.5 (CH), 37.3 (CH), 34.21
(CH2), 34.15 (CH2), 34.0 (CH2), 33.9 (CH2, overlapping signals), 33.8
(CH2), 33.4 (CH2), 31.9 (CH2), 28.0 (CH), 24.4 (CH2), 23.7 (CH2), 22.7
(CH3), 7.8 ppm (CH2); HRMS (MALDI): m/z: calcd for C75H152I:
1180.0933 [M+H]+; found: 1180.0933.
2,5-Bis[7-methyl-3-(4-methylpentyl)octyloxy]-1,4-diiodobenzene (34c)
K2CO3 (0.23 g, 1.66 mmol) was added to a solution of phenol 33 (0.10 g,
0.28 mmol) and G1-Br (29) (0.18 g, 0.61 mmol) in DMF (10 mL). The
mixture was stirred at 508C for 4 h under argon. After most of the sol-
vent was removed in vacuo, the residue was washed with CH2Cl2 three
times. The combined organic phase was washed with brine, dried MgSO4,
and concentrated in vacuo. The residue was purified by chromatography
(petroleum ether/CH2Cl2 =1:1) to provide compound 34c (0.18 g, 85%)
as a colorless oil. 1H NMR (400 MHz, CDCl3, 258C, TMS): d=7.18 (s,
2H), 3.95 (t, J=6.4 Hz, 4H), 1.74–1.83 (m, 4H), 1.51–1.62 (m, 6H), 1.15–
1.31 (m, 24H), 0.87 ppm (t, J=6.8 Hz, 24H); 13C NMR (100 MHz,
CDCl3, 258C, TMS): d=152.9 (C), 122.7 (CH), 86.2 (C), 68.7 (CH2), 39.4
(CH2), 37.3 (CH2), 34.5 (CH), 34.0 (CH2), 28.0 (CH), 24.4 (CH2),
22.7 ppm (CH3); MS (MALDI): m/z: 782 [M]+; HRMS (MALDI): m/z:
calcd for C36H64I2O2Na: 805.2888 [M+Na]+; found: 805.2889.
[8-methyl-4-(4-methylpentyl)nonyl]-4-{12-methyl-8-(4-methylpentyl)-4-[8-
methyl-4-(4-methylpentyl)nonyl]tridecyl}heptadecyl}-icosan-1-ol (5)
2,5-Bis{11-methyl-7-(4-methylpentyl)-3-[8-methyl-4-(4-
methylpentyl)nonyl] dodecyloxy}-1,4-diiodobenzene (34d)
Similar to the preceding procedure for the preparation of alcohol 12, diol
26 (0.20 g, 0.09 mmol) was treated with Et3SiH (0.03 mL, 0.19 mmol) and
TFA (0.06 mL, 0.86 mmol) in CH2Cl2 (5 mL), then hydrogenated in a
mixture of solvent (AcOEt/MeOH=7:1, 8 mL) to provide G4-OH (5)
According to the preceding procedure for the preparation of compound
34c, phenol 33 (0.02 g, 0.06 mmol) and G2-I (30) (0.08 g, 0.12 mmol) pro-
vided compound 34d (0.06 g, 83%) as
a
colorless oil. 1H NMR
1
(0.15 g, 80%) as a colorless oil. H NMR (400 MHz, CDCl3, 258C, TMS):
(400 MHz, CDCl3, 258C, TMS): d=7.18 (s, 2H), 3.95 (t, J=6.8 Hz, 4H),
1.75–1.80 (m, 4H), 1.49–1.64 (m, 14H), 1.12–1.29 (m, 72H), 0.87 ppm (t,
J=6.4 Hz, 48H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=152.9
(C), 122.7 (CH), 86.2 (C), 68.7 (CH2), 39.5 (CH2), 37.5 (CH), 34.5 (CH),
34.2 (CH2), 34.1 (CH2), 34.0 (CH2), 33.2 (CH2), 28.0 (CH), 24.4 (CH2),
23.7 (CH2), 22.7 ppm (CH3); MS (MALDI): m/z: 1343 [M]+; HRMS
(MALDI): m/z: calcd for C76H144I2O2Na: 1365.9148 [M+Na]+; found:
1365.9150.
d=3.67 (t, J=7.2 Hz, 2H), 1.50–1.56 (m, 20H), 1.11–1.24 (m, 194H),
0.86 ppm (d, J=6.8 Hz, 96H); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d=61.3 (CH2), 39.5 (CH2), 37.6 (CH), 37.5 (CH), 37.4 (CH), 37.0 (CH2),
34.5 (CH), 34.4 (CH2), 34.24 (CH2), 34.15 (CH2), 34.0 (CH2 overlapping
signals), 28.0 (CH), 24.4 (CH2), 23.7 (CH2), 22.7 ppm (CH3); HRMS
(MALDI): m/z: calcd for C155H313O: 2191.4436 [M+H]+; found:
2191.4437.
1-Bromo-7-methyl-3-(4-methylpentyl)octane (29)
2,5-Bis{15-methyl-11-(4-methylpentyl)-7-[8-methyl-4-(4-
methylpentyl)nonyl]-3-{12-methyl-8-(4-methylpentyl)-4-[8-methyl-4-(4-
methylpentyl)nonyl]tridecyl} hexadecyloxy}-1,4-diiodobenzene ACTHNUTRGNE(NUG 34e)
According to the preceding procedure for the preparation of bromide 13,
G1-OH (2) (1.00 g, 4.38 mmol) provided bromide 29 (1.11 g, 87%) as a
colorless oil. 1H NMR (400 MHz, CDCl3, 258C, TMS): d=3.42 (t, J=
7.2 Hz, 2H), 1.79–1.84 (m, 2H), 1.48–1.56 (m, 3H), 1.12–1.27 (m, 12H),
0.86 ppm (t, J=6.8 Hz, 12H); 13C NMR (100 MHz, CDCl3, 258C, TMS):
According to the preceding procedure for the preparation of compound
34c, phenol 33 (0.02 g, 0.06 mmol) and G3-I (31) (0.14 g, 0.12 mmol) pro-
vided compound 34e (0.11 g, 81%) as
a
colorless oil. 1H NMR
Chem. Asian J. 2012, 7, 143 – 155
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
153

X.-P. Cao et al.
FULL PAPERS
(400 MHz, CDCl3, 258C, TMS): d=7.17 (s, 2H), 3.93 (t, J=6.4 Hz, 4H),
1.76–1.78 (m, 4H), 1.48–1.58 (m, 30H), 1.11–1.26 (m, 168H), 0.86 ppm (t,
J=6.4 Hz, 96H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=153.0
(C), 122.8 (CH), 86.3 (C), 68.8 (CH2), 39.5 (CH2), 37.5 (CH, overlapping
signals), 34.5 (CH), 34.2 (CH2), 34.1 (CH2), 34.0 (CH2), 33.9 (CH2, over-
lapping signals), 33.2 (CH2), 28.0 (CH), 24.5 (CH2), 24.4 (CH2), 23.7
(CH2), 22.7 ppm (CH3); HRMS (MALDI): m/z: calcd for
C156H304O2I2Na: 2487.1668 [M+Na]+; found: 2487.1670.
Acknowledgements
The authors are grateful to the National Basic Research Program of
China (973 Program, Grant No. 2010CB833200), the National Natural
Science Foundation of China (Grant Nos. 20972060 and 21061160494),
the Specialized Research Fund for the Doctoral Program of Higher Edu-
cation (Grant No. 20090211110007), and the 111 Project for continuing fi-
nancial support. We gratefully acknowledge Prof. Hak-Fun Chow of The
Chinese University of Hong Kong for his helpful guidance in the prepa-
ration of the manuscript. We also thank Dr. M. Letzel, Bielefeld Univer-
sity, Germany, for accurate mass measurements.
1,4-Bis(4-acetylthiophenylethynyl)-2,5-bis[7-methyl-3-(4-
methylpentyl)octyloxy] benzene (28c)
Diisopropylamine (0.5 mL) was added to a solution of compound 34c
(0.10 g, 0.13 mmol), bis(triphenylphosphine)palladium(II) chloride (9 mg,
0.01 mmol), and CuI (1 mg, 0.006 mmol) in THF (10 mL) under an at-
mosphere of hydrogen. After the mixture was stirred for 1 h, a solution
of acetylene 35 (0.07 g, 0.38 mmol) in H2-deggased THF (5 mL) was
added. The reaction mixture was stirred under an atmosphere of hydro-
gen for 24 h at 508C, and then concentrated in vacuo. The residue was
purified by chromatography (petroleum ether/CH2Cl2 =1:1 slowly in-
creased to CH2Cl2) to provide compound 28c (0.08 g, 72%) as a primrose
yellow solid. M.p. 89–918C; 1H NMR (400 MHz, CDCl3, 258C, TMS):
d=7.55 (d, J=8.0 Hz, 4H), 7.38 (d, J=8.4 Hz, 4H), 7.02 (s, 2H), 4.05 (t,
J=6.8 Hz, 4H), 2.44 (s, 6H), 1.79–1.84 (m, 4H), 1.45–1.64 (m, 6H), 1.13–
1.30 (m, 24H), 0.83 ppm (d, J=6.4 Hz, 24H); 13C NMR (100 MHz,
CDCl3, 258C, TMS): d=193.4 (C), 153.6 (C), 134.1 (CH), 132.1 (CH),
128.0 (C), 124.7 (C), 116.8 (CH), 113.8 (C), 94.1 (C), 87.7 (C), 68.0
(CH2), 39.4 (CH2), 34.6 (CH), 34.0 (CH2), 33.3 (CH2), 30.3 (CH3), 28.0
(CH), 24.4 (CH2), 22.7 ppm (CH3); MS (MALDI): m/z: 879 [M]+;
HRMS (MALDI): m/z: calcd for C56H78O4S2: 878.5336 [M]+; found:
878.5341.
[1] a) J. Issberner, R. Moors, F. Vçgtle, Angew. Chem. 1994, 106, 2507–
2514; Angew. Chem. Int. Ed. Engl. 1995, 33, 2413–2420; b) G. R.
Newkome, E. He, C. N. Moorefield, Chem. Rev. 1999, 99, 1689–
1746.
[2] E. Buhleier, W. Wehner, F. Vçgtle, Synthesis 1978, 155–158.
[3] G. R. Newkome, Z. Yao, G. R. Baker, V. K. Gupta, J. Org. Chem.
1985, 50, 2003–2004.
[4] D. A. Tomalia, H. Baker, J. Dewald, M. Hall, G. Kallos, S. Martin, J.
Roeck, J. Ryder, P. Smith, Polym. J. 1985, 17, 117–132.
[5] a) A. W. Bosman, H. M. Janssen, E. W. Meijer, Chem. Rev. 1999, 99,
1665–1688; b) D. V. McGrath, Mol. Pharm. 2005, 2, 253–263; c) F.
Zeng, S. C. Zimmerman, Chem. Rev. 1997, 97, 1681–1712.
[6] M. Fischer, F. Vçgtle, Angew. Chem. 1999, 111, 934–955; Angew.
Chem. Int. Ed. 1999, 38, 884–905.
[7] a) M. Liu, K. Kono, J. M. J. Frꢁchet, J. Controlled Release 2000, 65,
121–131; b) M. Freemantle, Chem. Eng. News 1999, 77, 27–34.
[8] a) M. T. Reetz, G. Lohmer, R. Schwickardi, Angew. Chem. 1997,
109, 1559–1562; Angew. Chem. Int. Ed. Engl. 1997, 36, 1526–1529;
b) J. W. J. Knapen, A. W. van der Made, J. C. de Wilde, P. W. N. M.
van Leeuwen, P. Wijkens, D. M. Grove, G. van Koten, Nature 1994,
372, 659–663.
1,4-Bis(4-acetylthiophenylethynyl)-2,5-bis{11-methyl-7-(4-methylpentyl)-3-
[8-methyl-4-(4-methylpentyl)nonyl]dodecyloxy}benzene (28d)
According to the preceding procedure for the preparation of compound
28c, compound 34d (0.10 g, 0.07 mmol) and acetylene 35 (0.04 g,
0.22 mmol) provided compound 28d (0.05 g, 48%) as a primrose yellow
solid. M.p. 51–528C; 1H NMR (400 MHz, CDCl3, 258C, TMS): d=7.54
(d, J=8.0 Hz, 4H), 7.38 (d, J=8.4 Hz, 4H), 7.01 (s, 2H), 4.05 (t, J=
6.8 Hz, 4H), 2.43 (s, 6H), 1.80–1.85 (m, 6H), 1.46–1.66 (m, 12H), 1.13–
1.30 (m, 72H), 0.85 ppm (d, J=6.8 Hz, 48H); 13C NMR (100 MHz,
CDCl3, 258C, TMS): d=193.3 (C), 153.7 (C), 134.1 (CH), 132.1 (CH),
128.0 (C), 124.7 (C), 116.7 (CH), 113.7 (C), 94.2 (C), 87.7 (C), 67.9
(CH2), 39.5 (CH2), 37.5 (CH), 34.6 (CH), 34.2 (CH2), 34.1 (CH2), 33.9
(CH2), 33.3 (CH2), 30.3 (CH3), 28.0 (CH), 24.4 (CH2), 23.7 (CH2),
22.7 ppm (CH3); MS (MALDI): m/z: 1439 [M]+; HRMS (MALDI): m/z:
calcd for C96H158O4S2: 1439.1596 [M]+; found: 1439.1587.
[9] V. Balzani, S. Campagna, G. Denti, A. Juris, S. Serroni, M. Venturi,
Acc. Chem. Res. 1998, 31, 26–34.
[10] A. S. Kovvali, H. Chen, K. K. Sirkar, J. Am. Chem. Soc. 2000, 122,
7594–7595.
[11] a) M. J. Laufersweiler, J. M. Rohde, J.-L. Chaumette, D. Sarazin,
J. R. Parquette, J. Org. Chem. 2001, 66, 6440–6452; b) B.-K. Cho, A.
Jain, J. Nieberle, S. Mahajan, U. Wiesner, S. M. Gruner, S. Tꢃrk,
H. J. Rꢄder, Macromolecules 2004, 37, 4227–4234; c) D. R. Vutu-
kuri, S. Basu, S. Thayumanavan, J. Am. Chem. Soc. 2004, 126,
15636–16537; d) A. Gomez-Escudero, M. A. Azagarsamy, N.
Theddu, R. W. Vachet, S. Thayumanavan, J. Am. Chem. Soc. 2008,
130, 11156–11163.
[12] a) D. Joester, M. Losson, R. Pugin, H. Heinzelmann, E. Walter,
H. P. Merkle, F. Diederich, Angew. Chem. 2003, 115, 1524–1528;
Angew. Chem. Int. Ed. 2003, 42, 1486–1490; b) C. Loup, M.-A.
Zanta, A.-M. Caminade, J.-P. Majoral, B. Meunier, Chem. Eur. J.
1999, 5, 3644–3650; c) M. Guillot-Nieckowski, D. Joester, M. Stçhr,
M. Losson, M. Adrian, B. Wagner, M. Kansy, H. Heinzelmann, R.
Pugin, F. Diederich, J.-L. Gallani, Langmuir 2007, 23, 737–746.
[13] a) J.-J. Lee, W. T. Ford, J. A. Moore, Y. Li, Macromolecules 1994, 27,
4632–4634; b) S. Hecht, J. M. J. Frꢁchet, J. Am. Chem. Soc. 2001,
123, 6959–6960; c) B. Helms, C. O. Liang, C. J. Hawker, J. M. J. Frꢁ-
chet, Macromolecules 2005, 38, 5411–5415.
1,4-Bis(4-acetylthiophenylethynyl)-2,5-bis{15-methyl-11-(4-methylpentyl)-
7-[8-methyl-4-(4-methylpentyl)nonyl]-3-{12-methyl-8-(4-methylpentyl)-4-
[8-methyl-4-(4-methylpentyl)nonyl]tridecyl}hexadecyloxy} (28e)
According to the preceding procedure for the preparation of compound
28c, compound 34e (0.10 g, 0.04 mmol) and acetylene 35 (0.02 g,
0.12 mmol) provided compound 28e (0.04 g, 43%) as a primrose yellow
solid. M.p. 32–338C; 1H NMR (400 MHz, CDCl3, 258C, TMS): d=7.53
(d, J=8.4 Hz, 4H), 7.37 (d, J=8.4 Hz, 4H), 7.00 (s, 2H), 4.05 (t, J=
6.8 Hz, 4H), 2.43 (s, 6H), 1.82–1.84 (m, 4H), 1.49–1.55 (m, 30H), 1.10–
1.26 (m, 168H), 0.85 ppm (d, J=6.4 Hz, 96H); 13C NMR (100 MHz,
CDCl3, 258C, TMS): d=193.3 (C), 153.6 (C), 134.1 (CH), 132.1 (CH),
128.0 (C), 124.7 (C), 116.7 (CH), 113.8 (C), 94.2 (C), 87.7 (C), 67.9
(CH2), 39.5 (CH2), 37.5 (CH, overlapping signals), 34.3 (CH), 33.9 (CH2,
overlapping signals), 30.3 (CH3), 29.7 (CH2), 27.9 (CH), 24.4 (CH2), 23.7
(CH2), 22.7 ppm (CH3); HRMS (MALDI): m/z: calcd for C176H318O4S2:
2560.4116 [M]+; found: 2560.4118.
[14] a) S. Svenson, D. A. Tomalia, Adv. Drug Delivery Rev. 2005, 57,
2106–2129; b) S. R. Meyers, F. S. Juhn, A. P. Griset, N. R. Luman,
M. W. Grinstaff, J. Am. Chem. Soc. 2008, 130, 14444–14445.
[15] a) G. R. Newkome, C. N. Moorefield, G. R. Baker, M. J. Saunders,
S. H. Grossman, Angew. Chem. 1991, 103, 1207–1209; Angew.
Chem. Int. Ed. Engl. 1991, 30, 1178–1180; b) Y. Pan, W. T. Ford,
Macromolecules 2000, 33, 3731–3738.
[16] a) A. P. H. J. Schenning, C. Elissen-Romꢅn, J.-W. Weener,
M. W. P. L. Baars, S. J. van der Gaast, E. W. Meijer, J. Am. Chem.
Soc. 1998, 120, 8199–8208; b) N. R. Luman, M. W. Grinstaff, Org.
Lett. 2005, 7, 4863–4866.
154
www.chemasianj.org
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2012, 7, 143 – 155

Synthesis of Polyisoprene Terpenoid Dendrons
[17] G. R. Newkome, C. N. Moorefield, G. R. Baker, A. L. Johnson,
R. K. Behera, Angew. Chem. 1991, 103, 1205–1207; Angew. Chem.
Int. Ed. Engl. 1991, 30, 1176–1178.
[18] H.-F. Chow, K.-F. Ng, Z.-Y. Wang, C.-H. Wong, T. Luk, C.-M. Lo,
Y.-Y. Yang, Org. Lett. 2006, 8, 471–474.
[19] Z.-F. Shi, W.-Y. Chai, P. An, X.-P. Cao, Org. Lett. 2009, 11, 4394–
4397.
[20] J. D. Connolly, R. A. Hill, Dictionary of Terpenoids, London, Chap-
man and Hall, 1991.
Chem. 2007, 72, 10272–10275; c) L. Z. Gong, L. Pu, Tetrahedron
Lett. 2001, 42, 7337–7340.
[32] a) S. K. Deb, T. M. Maddux, L. Yu, J. Am. Chem. Soc. 1997, 119,
9079–9080; b) T. Gu, P. Ceroni, G. Marconi, N. Armaroli, J.-F. Nier-
engarten, J. Org. Chem. 2001, 66, 6432–6439; c) E. Dꢆez-Barra, J. C.
Garcꢆa-Martꢆnez, S. Merino, R. del Rey, J. Rodrꢆguez-Lꢇpez, P.
Sꢅnchez-Verdffl, J. Tejeda, J. Org. Chem. 2001, 66, 5664–5670; d) H.-
F. Chow, M.-K. Ng, C.-W. Leung, G.-X. Wang, J. Am. Chem. Soc.
2004, 126, 12907–12915.
[21] G. Egloff, M. Herrman, B. L. Levinson, M. F. Dull, Chem. Rev. 1934,
14, 287–383.
[33] Z. Xu, J. S. Moore, Angew. Chem. 1993, 105, 261–264; Angew.
Chem. Int. Ed. Engl. 1993, 32, 246–248.
[22] a) C. D. Poulter, H. C. Rilling, Acc. Chem. Res. 1978, 11, 307–313;
b) G. Cainelli, G. Cardillo, Acc. Chem. Res. 1981, 14, 89–94.
[23] D. J. McGarvey, R. Croteau, Plant Cell 1995, 7, 1015–1026.
[24] R. C. Palmer, Ind. Eng. Chem. 1942, 34, 1028–1034.
[25] O. A. Pickett, J. M. Peterson, Ind. Eng. Chem. 1929, 21, 325–326.
[26] a) L. J. Kitchen, J. Am. Chem. Soc. 1948, 70, 3608–3610; b) W. B.
Wheatley, W. E. Fitzgibbon, L. C. Cheney, S. B. Binkley, J. Am.
Chem. Soc. 1951, 73, 229–232.
[27] H. Howell, G. S. Fisher, J. Am. Chem. Soc. 1958, 80, 6316–6319.
[28] R. L. Bateman, A. R. Day, J. Am. Chem. Soc. 1935, 57, 2496–2498.
[29] J. N. Borglin, Ind. Eng. Chem. 1936, 28, 31–32.
[30] V. M. Loeblich, F. C. Magne, R. Mod, Ind. Eng. Chem. 1955, 47,
855–858.
[34] Z.-F. Shi, L.-J. Wang, H. Wang, X.-P. Cao, H-L. Zhang, Org. Lett.
2007, 9, 595–598.
[35] A. B. Charette, P. Chua, Synlett 1998, 163–165.
[36] H. P. Acharya, Y. Kobayashi, Tetrahedron 2006, 62, 3329–3343.
[37] H. Sajiki, K. Hirota, Tetrahedron 1998, 54, 13981–13996.
[38] J. J. H. Nusselder, J. B. F. N. Engberts, Langmuir 1991, 7, 2089–2096.
[39] J. E. Hallgren, G. M. Lucas, Tetrahedron Lett. 1980, 21, 3951–3954.
[40] F. Machrouhi, B. Hamann, J.-L. Namy, H. B. Kagan, Synlett 1996,
633–634.
[41] a) H. Uchiro, S. Kobayashi, Tetrahedron Lett. 1999, 40, 3179–3182;
b) D. T. Gryko, C. Clausen, K. M. Roth, N. Dontha, D. F. Bocian,
W. G. Kuhr, J. S. Lindsey, J. Org. Chem. 2000, 65, 7345–7355.
[31] a) F. Morgenroth, E. Reuther, K. Mꢃllen, Angew. Chem. 1997, 109,
647–649; Angew. Chem. Int. Ed. Engl. 1997, 36, 631–634; b) A. Op-
eramolla, O. H. Omar, F. Babudri, G. M. Farinola, F. Naso, J. Org.
Received: May 24, 2011
Published online: October 27, 2011
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