Design and synthesis of readily degradable acyloxysilane dendrimers

Article abstract of DOI:10.1016/j.tet.2011.07.068

Two types of dendrimers with AB₂ branching, one with acyloxysilanes at the branching position (V type) and the other at the non-branching position (Y type), were synthesized using hydrosilylation with chlorosilanes followed by heterofunctional condensation with olefin-functional carboxylic acids, and examined as readily degradable template materials. The V type dendrimer was much more susceptible to ligand redistribution with chlorosilanes during preparation, whereas the Y type was less. The acyloxysilane linkages in these dendrimers could be cleaved readily by alcoholysis or hydrolysis on demand, making for suitable templates.

Full text of DOI:10.1016/j.tet.2011.07.068

Tetrahedron 67 (2011) 7502e7509
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Design and synthesis of readily degradable acyloxysilane dendrimers
a
b
b
b,
*
Christopher M. Downing , Michael N. Missaghi , Mayfair C. Kung , Harold H. Kung
a
Department of Chemistry, Northwestern University, Evanston, IL 60208, USA
Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, E136, Evanston, IL 60208, USA
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Two types of dendrimers with AB2 branching, one with acyloxysilanes at the branching position (V type)
and the other at the non-branching position (Y type), were synthesized using hydrosilylation with
chlorosilanes followed by heterofunctional condensation with olefin-functional carboxylic acids, and
examined as readily degradable template materials. The V type dendrimer was much more susceptible to
ligand redistribution with chlorosilanes during preparation, whereas the Y type was less. The acylox-
ysilane linkages in these dendrimers could be cleaved readily by alcoholysis or hydrolysis on demand,
making for suitable templates.
Received 23 December 2010
Received in revised form 19 July 2011
Accepted 20 July 2011
Available online 27 July 2011
Keywords:
Acyloxysilane
Degradable dendrimer
Ligand redistribution
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
reactivity can be tuned by changing the substituent groups, through
increasing steric bulk or different electronic contributions. Acylox-
Cleavable or degradable dendritic structures (including den-
drimers, dendrons, and hyper-branched polymers) have been ex-
ysilanes are susceptible to nucleophilic attack at either the Si or the
11
C]O, depending on the nucleophile. In addition, redistribution of
silicon substituents, which commonly includes R, H, Cl, or OR (alk-
oxy, silanol, siloxy) substituents, has been observed that can be
1
plored for various applications, such as drug and gene delivery,
2
release of fragrances and flavors, generation of materials with
microcavities,3 and molecular imprinting, in which these struc-
4
initiated by thermolysis or catalysis. Such exchange of chlor-
12
5
tures function as a ‘covalent reservoir. Ideally, the degradation of
osilanes and acyloxysilanes depends on steric and electronic effects
13
these structures should be tunable, and occur on demand under
relatively mild conditions. The degradation conditions need to be
orthogonal to reactions employed in the synthesis of the structures.
To date, most degradation reactions rely on hydrolyzable link-
at both silicon centers.
Here, we report positioning the acyloxysilane bonds at branch-
ing (V type) and non-branching (Y type) silicon in the preparation of
easily degradable dendrimers, in order to determine the versatility
and/or limitations of each. Dendrimer generation growth was
6
5
ages, typically carbonyl based, including esters, amides, and car-
7
bamates. Often, harsh degradation conditions are needed, such as
accomplished using a two-step process: platinum-catalyzed
treatment with strong base or strong acid, which preclude the in-
corporation of some functional groups and place restrictions on
reactions for dendrimer synthesis or modification. For example, we
previously found that the conditions needed for degradation of
carbamate dendrimers limited the cross-linking methods that could
hydrosilylation with chlorosilanes and heterofunctional condensa-
tion at the chlorosilanes with olefinic carboxylic acid monomers in
the presence of amine base, a strategy similar to the preparation of
14
a variety of carbosilane-based dendrimers and alkoxysilane den-
15
drimers. This two-step process was chosen to minimize self-
termination events, such as cyclization.
8
be used in dendrimer modification. Milder, anhydrous degradation
reactions would permit incorporation of functional groups and
synthetic methods that have not been previously accessible.
2
2
. Results and discussion
3
We investigated the use of acyloxysilane bonds, R SieOe(C]O)-
R, in the construction of degradable dendrimer backbones. Also
known as silyl esters, these bonds are appealing for degradable
templates since they have been shown to cleave easily by alcohol-
ysis and hydrolysis.9 These reactions are quantitative, and the
.1. Acyloxysilane dendrimer synthesis strategy
In V type acyloxysilane dendrimers (Scheme 1), branching oc-
,10
curs at the silyl ester Si. Thus, a branching monomeric building unit
was used that possessed one hydride and two chloro groups (e.g.,
dichlorosilane), with the fourth ligand at Si reserved for tuning
selectivity and reactivity. Generation growth was accomplished by
hydrosilylation of the branching monomeric unit with the previous
*
Corresponding author. Tel.: þ1 847 491 7492; fax: þ1 847 4671018; e-mail ad-
dress: hkung@northwestern.edu (H.H. Kung).
0
040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.07.068

C.M. Downing et al. / Tetrahedron 67 (2011) 7502e7509
7503
Scheme 1. Synthesis of V type acyloxysilane dendrimers by repeated cycles of catalyzed (Karstedt) hydrosilylation with dichloroethylsilane (half-generation dendrimers 1, 3, 5), and
condensation with 4-pentenoic acid in the presence of pyridine (full-generation dendrimers 2, 4, 6).
ꢀ
1
generation to form the half generation, and full generation was
completed by heterofunctional condensation with 4-pentenoic acid
in the presence of pyridine, which promoted condensation and
formed the byproduct pyridinium chloride, an easily removed salt.
Karstedt catalyst in THF at 40 C. H NMR showed complete con-
version of tetravinylsilane within 4 h. After purification by evacu-
ation of volatile components, the resulting clear oil showed
complete disappearance of vinyl olefin resonances in the high fre-
4
-Pentenoic acid was selected as the carboxylic acid monomer due
quency region (
pearance of new resonances in the methylene region (
0.67 ppm) (Fig. S3). The product contained 85% 1 by -addition and
15% of its isomer by -addition. The competition between - and
d
6.18 and 5.83 ppm) and the corresponding ap-
to commercial availability and stability on storage.
d
0.89 and
For Y type acyloxysilane dendrimers (Scheme 2), branching oc-
curs at Si atoms away from the silyl ester. Thus, two separate silicon
centers are involved, which imparts more control on the steric bulk
and provides an opportunity for further functionalization for spe-
cific applications. Generation growth was accomplished by hydro-
silylation of chlorodimethylsilane, followed by heterocondensation
with (diallylmethyl)silyl-4-butanoic acid 16. The structure can be
modified by varying the carbon chain length, increasing the
branching to three, and varying the olefinic branch of the acid.
In both examples, tetravinylsilane was chosen to be the core,
which has four olefins and tetrahedral symmetry. Hydrosilylation
b
a
a
b-
hydrosilylation was both temperature- and solvent-dependent, and
ꢀ
was shown to favor
b
-addition in THF at 40 C, as reported by
17
Seyferth and co-workers. 1 was highly moisture sensitive and was
kept under rigorous air-free conditions.
Preparation of first-generation dendrimer, 2, was completed by
condensation of 1 with 3 equiv of 4-penteneoic acid in anhydrous
hexanes in the presence of 3 equivof pyridine (perchlorosilane). The
HClepyridine salt was removed by air-free filtration over a medium
frit glass filter. Afterward, the residual 4-penteneoic acid was sily-
lated with chlorotrimethylsilane to reduce the boiling point, again in
the presence of excess pyridine as the base. After a second filtration
of HClepyridine salts, all of the volatiles including the silylated 4-
pentenoic acid were evacuated. It is important to exclude moisture
during preparation, purification, analysis, and storage to avoid
degradation of the acyloxysilane dendrimers.
2 3
was performed with the Karstedt catalyst (Pt(0) DVTMS , divinyl-
tetramethyldisiloxane) in tetrahydrofuran (THF). From its X-ray
crystal structure, the Karstedt catalyst has both chelating and
bridging divinyltetramethyldisiloxane ligands at the Pt centers
16
prior to reaction (Fig. 1).
2
.2. V Type dendrimer synthesis
These two synthesis steps were easily scalable, particularly the
hydrosilylation reaction. The preparations of 3 and 4, as well as
higher generations, such as third-generation 6 (Fig. S2), could be
carried out in a similar manner by repeating these two steps.
Half-generation dendrimer, 1, was prepared by hydrosilylation
of tetravinylsilane by dichloroethylsilane in the presence of the

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C.M. Downing et al. / Tetrahedron 67 (2011) 7502e7509
Scheme 2. Synthesis of Y type acyloxysilane dendrimer by repeated cycles of catalyzed (Karstedt) hydrosilylation with chlorodimethylsilane, followed by condensation with
(
diallylmethyl)silyl-4-butanoic acid 16 in the presence of pyridine.
macromolecules, such as broad resonances and loss of splitting
patterns. The major difference between 2 and 4 was the new
methylene resonances at
d 1.60 and 1.40 ppm for 4, due to hydro-
silylation of the terminal olefin of 2. The spectrum of the third-
generation dendrimer (Fig. S1) was nearly identical to 4 except for
the integrals of the resonances, consistent with expectation due to
branching generations. The methylene protons of the core (
.60 ppm and 0.45 ppm) were difficult to observe, due to the large
number of protons of the ethylsilane groups at 1.00 ppm.
d
0
Fig. 1. Structure of Karstedt catalyst.
d
Ligand redistribution was encountered in generation growth
hydrosilylation reactions in the preparation of 3 (1.5-generation)
and 5 (2.5-generation). Detection of the extent of ligand re-
distribution immediately after reaction was difficult as further re-
distribution might have taken place during purification. For
products after purification, redistribution could be readily detected
1H NMR was not very useful in identifying ligand exchange or
distinguishing products of a- and b-hydrosilylation. Fig. 2 shows
the spectra for first (2), second (4), and third-generation (6) full-
dendrimers. They all exhibited the common features of
2
9
with Si NMR. Fig. 3 shows the spectrum of the purified product 3,
2
4
6
6
.0 5.6 5.2 4.8 4.4 4.0 3.6 3.2 2.8 2.4 2.0 1.6 1.2 0.8 0.4
0
Fig. 2. 1H NMR of V type dendrimers. Top to bottom: first- (2), second- (4), and third-
generation dendrimers (6).
Fig. 3. 29Si NMR of first-generation dendrimer (2), dichloroethylsilane (DCES), and the
product in the preparation of 1.5-generation (3).

C.M. Downing et al. / Tetrahedron 67 (2011) 7502e7509
7505
after evacuation of excess dichloroethylsilane and THF. For 2, res-
onances were found at 11 ppm (core) and 3 ppm (geminal acy-
loxysilane), while dichloroethylsilane resonance was at 13 ppm. For
the reaction product between these two, in addition to the expec-
Table 1
Exchange of 2 with various dichlorosilanes. Compound 2 (0.050 mL) was dissolved
d
in 0.380 mL of CDCl
heated at 40 C for 3 h
3
followed by addition of 0.50 mL of respective dichlorosilanes,
ꢀ
Dichlorosilane
% Exchanged
Dichlorosilane
% Exchanged
25
ted resonances at
nance also appeared at
d
34, 11 and 3 ppm assigned to 3, another reso-
19 ppm, which was about halfway
d
between the Si in dichlorosilanes and the dichlorosilyl groups in 3.
We assign this to Si in mixed acyloxychlorosilane species, with one
chloro- and one acyloxy-substituent, which was formed by ligand
redistribution. The resulting material contained defective den-
drimers of 3.
100
75
15
0
2
.3. Ligand redistribution study
For the syntheses in Schemes 1 and 2, ligand exchange processes
of interest were examined using model compound 10 and
dichloroethylsilane (Fig. 4). Silane 10 mimics a segment of a V type
dendrimer. In an NMR tube, 10 was dissolved in CDCl
oethylsilane was added, and the reaction was monitored by Si
NMR. The 29Si NMR resonance for 10 appeared at
5 ppm, and for
dichloroethylsilane at 13 ppm. After 1 h, two new resonances
were observed at
3
, dichlor-
2
.4. V Type dendrimer degradation
2
9
d
V type dendrimers could be degraded under mild conditions by
d
treatment with anhydrous methanol to form methoxysilanes and
free carboxylic acids. Being less reactive or prone to gelation than
silanols, methoxysilanes are preferred degradation products that
are expected to be advantageous for post-synthetic functionaliza-
tion. Degradation by methanolysis of both first and second-
generation dendrimers, 2 and 4 (Scheme 3) occurred rapidly at
room temperature. Only degradation at the silyl ester bond was
observed. The degradation reactions could be monitored accurately
d
21 and ꢁ0.35 ppm, which were attributed to
compounds 11 and 12, respectively. After 24 h, the resonance of
dichloroethylsilane disappeared, and another two new resonances
appeared at
d
36 and ꢁ13.7 ppm, which were attributed to doubly
exchanged products, dichlorodiethylsilane and 13, respectively.
Since 10 mimics the products of generation growth, condensation
of a dichlorosilyl fragment with 4-pentenoic acid, the single ex-
change products would be the same as incomplete condensation,
and double exchange products would reverse the condensation
reaction.
13
1
by C NMR. Although H NMR contained analogous results, sepa-
rate identification of methyl protons of methoxysilanes and
methanol was difficult because of similar frequency shifts. The
carbonyl carbons for dendrimer 4 were at
-pentenoic acid was observed at 180 ppm. After methanolysis
Fig. 5), only two carbonyl resonances at 180 and 179 ppm were
d 173 and 172 ppm, while
4
d
(
d
observed. The shifts to lower frequencies from those of 4 indicated
replacement of the silyl ester bond with a less electron with-
drawing substituent, as expected for methanolysis. No other
products were detected.
Scheme 3. Degradation of 4 by methanolysis. R¼dendrimer arms.
Fig. 4. Ligand exchange of 10 with dichloroethylsilane.
Additional experiments were conducted in order to gain a better
insight into the extent of exchange during purification in the syn-
thesis of V type dendrimer by examining ligand exchange between
the first-generation dendrimer 2 and various dichlorosilanes with-
out the Karstedt catalyst. The results are shown in Table 1. Under
these conditions, dichloroethylsilane exchanged completely with 2.
Dichlorophenylsilane also exchanged rapidly with 2, though only to
Fig. 5. 13C NMR of 4 (top) and the product of methanolysis degradation (bottom)
(*toluene, -methanol).
7
5% under the same conditions. Exchange was observed with
2.5. Y Type dendrimer synthesis
dichlorodiorganyl silanes also, including dichloroethylmethylsilane
and dichlorodiethylsilane. Only with dichlorodiisopropylsilane was
there no observable exchange.
The divinylsilyl acid used for branching was synthesized
according to Scheme 4. (3-Chloropropyl)dichloromethylsilane was

7506
C.M. Downing et al. / Tetrahedron 67 (2011) 7502e7509
used as the starting compound, although other molecules with
different alkyl lengths or number of chlorosilane functional groups
can be used for different dendrimer architectures. Grignard sub-
stitution of the chlorosilane was performed to introduce the olefin
branches (step v). After purification, greater than 85% yield of
product 14 was obtained. Then, the alkyl chloride moiety was ac-
tivated with Mg to prepare a Grignard reagent, which was reacted
2
with CO , and worked up with HCl to yield the branching carboxylic
acid 16.
Fig. 7. 29Si NMR of divinylsilyl carboxylic acid 16 (top), half-generation 7 (middle) and
first-generation Y type dendrimer 8 (bottom).
Scheme 4. Synthesis of divinylsilyl carboxylic acid monomer 16 branching at chlor-
osilane, by Grignard substitution, followed by activation to Grignard, and then nu-
cleophilic attack of CO .
2
Attempts to grow the next generation were not successful be-
cause hydrosilylation of 8 with chlorodimethylsilane to form the
1
.5-generation dendrimer 9 could not be brought to completion.
Although new methylene resonances were observed around
1.00 ppm, the vinyl resonances at 6.10 and 5.72 ppm were still
Proton NMR of 14 showed vinyl resonances at
.75 ppm and three methylene resonances at 1.80, 0.76, and
.5 ppm (Fig. 6). For the divinyl acid 16, the vinyl resonances
d 6.11 and
d
d
5
3
d
observed. Increasing the temperature of hydrosilylation, addition of
more catalyst precursor, or longer reaction times did not increase
the yield of 1.5-generation dendrimer, which was estimated to be
less than 10%. Even though the reaction was not complete, analysis
indicated that no ligand redistribution had occurred during the
hydrosilylation step. Nonetheless, improvement in this step is
needed to bring the reaction to completion for the 1.5-generation
synthesis, or an efficient purification method needs to be devised.
Then, a purified 9 can be used to build the second-generation
dendrimer.
remained and the three methylene resonances shifted to lower
frequencies, especially the protons closest to chlorine, which shif-
ted to
132 and 136 ppm, and the carbonyl carbon at
dicating that the free carboxylic acid form was present.
d
2.4 ppm. 13C NMR of 16 showed the resonances of vinyls at
d
d 180 ppm, in-
3
. Conclusion
1
4
6
Acyloxysilyl bonds can be incorporated into dendrimers or
dendritic structures as an easily degradable bond. In principle,
dendrimer growth can be achieved, using reactions such as
hydrosilylation, without affecting the acyloxysilyl bond. However,
the side reaction of ligand redistribution at the Si atom limits the
generation growth process, since it results in loss of the acyloxysilyl
bond from the dendritic structure and formation of a defective
dendrimer. The ligand redistribution process can be minimized or
even avoided by using a combination of substituent steric and
electronic effects, and by designing the template dendrimer and
product materials to avoid easily exchanged species. This was
achieved with the Y type dendrimers with branching on the acid,
where only single acyloxysilane and single chlorosilane are present.
Nonetheless, the redistribution process restricts the types of den-
drimer that may be synthesized with perfection.
Results of this study suggest that an acyloxysilyl bond is best
applied as the final linkage before the ‘cargo’ in a degradable
template. Since the cleavage of acyloxysilane bonds is facile even
under mild conditions, the presence of a large variety of functional
groups can be tolerated, such as those used in hydrosilylation and
heterofunctional condensation for synthesis.
*
*
1
8
7
6
5
4
3
2
1
0
Fig. 6. 1H NMR of product 14 (top) and carboxylic acid 16 (bottom). (*THF).
The Y type dendrimer was prepared with a divergent synthesis
shown in Scheme 2, using tetravinylsilane as the core and 16 for
branching. First, 7 was prepared by hydrosilylation with chlor-
odimethylsilane using the Karstedt catalyst. The reaction pro-
ceeded to completion readily, and 7 was purified by evacuation of
volatiles. Then 7 was condensed with 16 in the presence of pyri-
dine, and the reaction mixture was treated with chloro-
trimethylsilane to cap the excess carboxylic acid. Pyridinium
chloride salt was filtered under moisture-free conditions, and all
volatiles were removed by evacuation to yield the first-generation
dendrimer 8. Complete removal of the excess divinylsilyl acid 16
was difficult, as the branching acid monomer remained high boil-
ing, even when capped as a trimethylsilyl ester. Nevertheless, it
could be accomplished by adding excess toluene and evacuation of
volatiles multiple times. Successful synthesis of 7 was confirmed by
multinuclear NMR analyses (Fig. 7). The Si spectrum of 16 had
a resonance at
ꢁ12 ppm. The half-generation dendrimer 7 had
two silicon resonances at 33 ppm (chlorosilane) and 10 ppm
core silicon). Condensation of 7 with 16 resulted in the new acy-
loxysilane in 8 with a resonance at 24 ppm, while the core
remained at 10 ppm and the vinylsilicon of the acid remained at
ꢁ12 ppm.
4. Experimental section
4.1. General
2
9
d
d
d
Solvents and chemicals were purchased (Aldrich Chemical) as
well as the Karstedt catalyst (Gelest). All chemicals were used as
supplied. Moisture-sensitive reagents were stored under N
2
in
a glovebox (Vacuum Atmospheres), and reactions were performed
with standard Schlenk techniques.
(
d
d
d

C.M. Downing et al. / Tetrahedron 67 (2011) 7502e7509
7507
NMR spectra were acquired with a Varian Inova 400 MHz in-
strument in the Institute for Molecular Structure Education and
Research Center at Northwestern University using the following
parameters: 1H: 400.14 MHz, 2 s recycle delay, internally refer-
32H), 2.37 (m, 48H), 1.65 (m, 16H), 1.45 (m, 16H), 1.00 (s, 76H), 0.80
13
(m, 8H), 0.54 (m, 8H). C NMR (CDCl
35.0, 28.9, 28.8, 28.1, 21.8, 13.2, 6.19, 6.04, 5.92, 5.72, 5.10. Si NMR
(CDCl ): 11.19, 3.87, 3.86. Anal. Calcd for C152 48Si13: C, 56.83;
H, 7.91, found: C, 54.19; H, 7.90.
3
): d 173.2, 136.8, 115.7, 35.3,
2
9
3
d
252
H O
13
1
enced to solvent; C: 100.63 MHz, H decoupled, 2 s recycle delay,
2
9
internally referenced to solvent; Si: 79.50 MHz, 45 s recycle delay
and externally referenced to tetramethylsilane in benzene-d
6
4.2.5. 2.5-Generation V dendrimer (5). Product 4 (1.28 g) was dis-
solved in toluene (12 mL), and Karstedt catalyst (0.015 mL, 2.1% Pt)
was added. Dichloroethylsilane (28 mmol, 3.40 mL, 3.70 g) was
added and the mixture was stirred for 15 min. Then the reaction
2
9
6 6
(C D ). All chemical shifts are reported in ppm. Si NMR RINEPT:
Using a Refocused INEPT (Insensitive Nuclei Enhanced by Polari-
zation Transfer) pulse sequence with the following parameters
18
ꢀ
d1¼13 d2¼0.0256 d3¼0.0176.
mixture was heated to 40 C and stirred for 4 h. All volatiles were
1
removed under vacuum, leaving light yellow oil, 5 (2.60 g). H NMR
4
.2. V Type dendrimer synthesis
3
(CDCl ): d 2.33 (m, 48H), 1.65 (m, 48H), 1.50 (m, 48H), 1.04 (m,
13
1
20H), 1.00 (m, 48H), 0.76 (m, 8H), 0.54 (m, 8H). C NMR (CDCl
3
):
173.0, 35.2, 27.6, 22.1, 19.7, 12.7, 6.26, 6.10, 5.94, 5.70. Si NMR
): 34.7, 19.5 (redistribution product), 19.3 (redistribution
2
9
4.2.1. 0.5-Generation V dendrimer (1). Tetravinylsilane (1 mmol,
d
0
.167 mL, 0.134 g) was dissolved in anhydrous THF (10 mL), fol-
(CDCl
3
d
lowed by the addition of Karstedt catalyst (0.010 mL, 2.1% Pt).
Slowly, dichloroethylsilane (6 mmol, 0.711 mL, 0.774 g) was added
to the reaction flask, which was then heated to 40 C for 5 h. Excess
product), 3.5, 3.0 (no core Si resonance observed). No useful MS or
elemental analysis was obtained due to the high reactivity of silyl
chloride with moisture.
ꢀ
silane and solvents were removed under reduced pressure,
1
resulting in clear oil (1.35 g). H NMR (CDCl
3
):
12.42,12.00, 6.36,1.74. Si
35.28, 11.33. No useful MS or elemental analysis was
obtained due to the high reactivity of silyl chloride with moisture.
d
1.09 (m, 20H), 0.90
4.2.6. Third-generation V dendrimer (6). Product 5 (1.30 g) was
dissolved in toluene (20 mL). Subsequently, pyridine (63 mmol,
5.0 mL, 4.89 g) was added to the reaction flask, followed by the
addition of 4-pentenoic acid (50 mmol, 5.00 mL, 4.90 g). The re-
action mixture was stirred for 3 h at room temperature, and then
chlorotrimethylsilane (12 mmol, 1.50 mL, 1.30 g) was added. The
pyridinium chloride salt was removed by air-free filtration, and
washed with hexane (two portions, 10 mL). All volatiles were
evacuated and then a fresh aliquot of toluene (6 mL) was added and
m, 8H), 0.67 (m, 8H). 1 C NMR (CDCl
3
29
(
3
): d
NMR (CDCl ):
3
d
4
.2.2. First-generation V dendrimer (2). Product 1 (1.35 g) was dis-
solved in anhydrous hexanes (15 mL). Subsequently pyridine
30 mmol, 2.4 mL, 2.35 g) was syringed into the flask, followed by
slow addition of 4-pentenoic acid (30 mmol, 3.0 mL, 2.94 g). The
reaction was stirred, at room temperature for 1 h, then chloro-
trimethylsilane (12 mmol, 1.5 mL, 1.30 g) was added, and stirring
was continued for 15 min. The pyridinium chloride salts were re-
moved by air-free filtration, and the captured salt was washed twice
with anhydrous hexanes (10 mL). All the filtrates were combined,
and the volatile components were removed under reduced pressure
(
the system evacuated again. The product third-generation den-
1
drimer was recovered as oil (2.30 g). H NMR (CDCl
3
):
d
5.83 (m,
32H), 5.05 (dd, J¼17.3, 10.1 Hz, 64H), 2.46 (m, 64H), 2.37 (m, 112),
1.65 (m, 48H), 1.45 (m, 48H), 1.00 (m, 188), 0.80 (m, 8H), 0.54 (m,
1
3
8H). C NMR (CDCl
28.1, 21.8, 13.2, 6.19, 6.04, 5.92, 5.72, 5.10. Si NMR (CDCl
3.26 (the resonance of the core Si was not observed). Anal. Calcd for
112Si29: C, 56.49; H, 7.88, found: C, 57.40; H, 8.24.
3
): d 173.2, 136.8, 115.7, 35.3, 35.0, 28.9, 28.8,
2
9
3
): d 3.48,
ꢀ
1
with gentle heating at 40 C (2.15 g). H NMR (CDCl
3
):
d 5.83 (m, 8H),
5
2
1
.05 (dd, J¼17.2, 10.4 Hz, 16H), 2.48 (m, 16H), 2.36 (m, 16H), 1.02 (m,
344 572
C H O
13
0H), 0.80 (m, 8H), 0.54 (m, 8H). C NMR (CDCl
3
):
d
172.12, 136.80,
): 11.20,
.40. LC/ESI-MS: m/z¼1179 (theor. 1160). Anal. Calcd for
: C, 57.90; H, 7.98, found: C, 52.56; H, 8.06.
2
9
16.00, 34.99, 29.05, 6.14, 5.55, 5.20, 1.80. Si NMR (CDCl
3
d
4.2.7. Degradation of dendrimers 2 and 4. Dendrimer 2 or 4
(0.100 mL) was dissolved in dichloromethane (2 mL). Then a sam-
ple of the mixture (0.100 mL) was injected into anhydrous metha-
3
C
56 92 5
H O16Si
2
nol (1 mL). This sample was then dried under N , and dissolved in
4.2.3. 1.5-Generation V dendrimer (3). Product 2 (1.16 g) was dis-
CDCl (0.500 mL).
3
solved in toluene (10 mL), and Karstedt catalyst (0.010 mL, 2.1% Pt)
was added. Subsequently dichloroethylsilane (14 mmol, 1.70 mL,
4.2.7.1. Degradation of 2. 1H NMR (CDCl
8H), 5.06 (dd, J¼17.3, 11.2 Hz,16H), 2.47 (m,16H), 2.40 (m, 16H),1.00
): d 9.14 (s, 8H), 5.86 (m,
3
1
.85 g) was added and the mixture was stirred for 15 min. Then the
ꢀ
13
reaction mixture was heated to 40 C and stirred for 4 h. All vola-
(m, 20H), 0.65 (m, 8H), 0.54 (m, 8H). C NMR (CDCl
3
):
d
179.0,
d 10.5,
2
9
tiles were removed under vacuum, leaving light yellow oil (2.16 g).
136.6, 115.8, 50.5, 33.5, 28.8, 6.80, 2.86. Si NMR (CDCl
3
):
1
H NMR (CDCl
6H), 1.10 (s, 40H), 1.00 (m, 16H), 0.80 (m, 8H), 0.60 (m, 8H).
NMR (CDCl ): 172.79, 35.11, 27.83, 22.19, 19.60, 12.63, 6.42, 6.16,
.58, 5.20, 1.32. Si NMR (CDCl
3
):
d
2.42 (t, J¼6.5 Hz, 16H), 1.71 (m, 16H), 1.58 (m,
ꢁ1.30, ꢁ11.2, ꢁ11.5.
13
1
C
d
4.2.7.2. Degradation of 4. 1H NMR (CDCl
3
): d 10.66 (s, 24H), 5.79
3
29
5
3
):
d
34.7, 19.6 (redistribution
(m, 16H), 5.00 (dd, J¼17.3, 11.2 Hz, 32H), 2.41 (m, 32H), 2.33 (m,
48H), 1.63 (m, 16H), 1.40 (m, 16H), 0.93 (t, J¼8.0 Hz, 24H), 0.61 (m,
product), 11.4, 3.11. No useful MS or elemental analysis was
obtained due to the high reactivity of silyl chloride with moisture.
13
3
32H), 0.48 (s, 16H). C NMR (CDCl ): d 180.3, 179.5, 136.5, 115.9,
2
9
3
3.9, 33.5, 28.7, 28.3, 22.5,11.3, 6.48 3.66. Si NMR (CDCl
3
):
d
ꢁ1.63,
4
.2.4. Second-generation V dendrimer (4). Product 3 (1.00 g) was
dissolved in toluene (20 mL). Then pyridine (30 mmol, 2.40 mL,
.35 g) was added to the reaction flask, followed by 4-pentenoic
ꢁ1.76, ꢁ10.7.
2
4.3. Y Type dendrimer synthesis
acid (25 mmol, 2.50 mL, 2.45 g). The reaction was stirred for 3 h
at room temperature when chlorotrimethylsilane (12 mmol,
4.3.1. Divinyl(3-chloropropyl)methylsilane (14). (3-Chloropropyl)
1
.50 mL, 1.30 g) was added. The pyridinium chloride salt was fil-
dichloromethylsilane (25 mmol, 4.00 mL, 4.82 g) was dissolved in
anhydrous THF (10 mL) and cooled to 0 C in an ice bath. Then,
vinylmagnesium bromide (55 mmol, 55.00 mL, 1 M THF solution)
was added dropwise over 30 min. The reaction was allowed to
warm to room temperature over 30 min, and excess Grignard re-
agent was neutralized with 1 M HCl (2 mL). Product 14 was
ꢀ
tered on the air-free filtration apparatus, and washed with two
portions hexane (10 mL). All volatiles were evacuated and then
a fresh aliquot of toluene (6 mmol) was added and the system
1
evacuated again. Product 4 was recovered as oil (1.28 g). H NMR
(
CDCl
3
):
d
5.83 (m, 16H), 5.05 (dd, J¼17.4, 10.1 Hz, 32H), 2.46 (m,

7508
C.M. Downing et al. / Tetrahedron 67 (2011) 7502e7509
extracted from the aqueous layer with cyclohexane (three portions,
5 mL). The organics were collected and dried with sodium sulfate,
filtered, and concentrated on a rotary-evaporator. The residual oil
(0.015 mL, 2.1% Pt) was added and, after 3 min, dimethyl-
chlorosilane (2.4 mmol, 0.266 mL, 0.227 g) was injected. After
15 min of stirring at room temperature, the reaction flask was
2
ꢀ
1
ꢀ
was distilled at (32 C, evacuated and closed) (3.31 g, 76% yield). H
NMR (CDCl ):
6.14 (dd, J¼19.7, 14.8 Hz, 2H), 6.05 (dd, J¼14.8,
.4 Hz, 2H), 5.75 (dd, J¼19.7, 4.4 Hz, 2H), 3.52 (t, J¼7.0 Hz, 2H), 1.80
heated to 40 C and stirred for 3 h. All volatiles were evacuated at
ꢀ
3
d
40 C, and multinuclear NMR analysis was performed on the re-
4
sidual brown (Pt agglomerates) oil 16. About 30% conversion of
olefins was accomplished under these conditions, by integral
analysis to dendrimer arms (no internal standard).
1
3
(
m, 2H), 0.76 (m, 2H), 0.17 (s, 3H). C NMR (CDCl
3
):
ꢁ12.12. Anal. Calcd
15SiCl: C, 55.00; H, 8.66, found: C, 55.49; H, 8.62.
d 136.35,133.64,
2
9
4
for C
8.06, 27.63, 11.89, ꢁ5.23. Si NMR (CDCl
3
): d
8
H
4.4. Redistribution reactions
4.3.2. Divinyl(4-butanoate)methylsilane (16). Magnesium turnings
(
17.7 mmol, 0.430 g) were added to a 3-neck flask equipped with
4
.4.1. Synthesis of diethylsilyldipentanoate (10). Dichlorodiethylsilane
a condenser, a stopcock to manifold, and a septum. The system was
heated to 80 C and evacuated for 30 min. Then anhydrous THF
(
1 mmol, 0.150 mL) was dissolved in toluene (6 mL), to which
pyridine (2.6 mmol, 0.260 mL, 0.54 g) and 4-pentenoic acid
2.5 mmol, 0.260 mL, 0.255 g) were added. The reaction was stirred
for 30 min, and then chlorotrimethylsilane (2.5 mmol, 0.200 mL,
.23 g) was added and stirred for 30 min. The pyridinium chloride
salts were filtered under air-free conditions, and the volatile com-
ꢀ
(
10 mL) was injected and refluxed for 10 min.1,2-Dibromoethane in
(
THF (1.77 mmol, 0.200 mL, 10% solution) was introduced under
reflux. Divinyl(3-chloropropyl)methylsilane 14 (16 mmol, 2.92 mL)
was added over 20 min, maintaining reflux. The reaction was
continuously refluxed for 30 min, until a dark brown-black solution
0
1
ponents were evacuated (0.278 g, 98% yield). H NMR (CDCl
d
3
):
resulted containing product 15. CO
into a Schlenk flask from an anhydrous CO
solution, as prepared, was syringed onto the CO
was warmed to room temperature. Sodium bicarbonate (5 mL, pH
0) solution was added and the mixture was washed with Et
three portions, 25 mL). Finally, 1 M HCl solution was added until
the aqueous phase pH reached 1, which allowed the acid 16 to be
2
(340 mmol, 15.0 g) was frozen
tank. The THF Grignard
and the mixture
5.80 (m, 2H), 5.00 (dd, 4H), 2.45 (m, 4H), 2.34 (m, 4H), 0.96 (m,
13
2
overlapped ethyl, 10H). C NMR (CDCl
2
3
):
5.28.
d 172.8, 136.7, 115.7, 34.9,
9.0, 5.92, 5.40. 29Si NMR (CDCl
3
): d
2
1
(
2
O
4.4.2. Redistribution of 10 with dichloroethylsilane. Product 10
(0.08 mL) was dissolved in CDCl
3
(0.750 mL) and dichloroethy-
lsilane (0.020 mL) was added. The reaction was analyzed at 1 h by
1
extracted with Et
2
O (2.48 g, 85% yield). H NMR (CDCl
3
):
d
6.13 (dd,
29
Si NMR. It contained four resonances attributed to four different
J¼19.7, 14.8 Hz, 2H), 6.03 (dd, J¼14.8, 4.4 Hz, 2H), 5.73 (dd, J¼19.7,
29
compounds, see Fig. 2, compound identified in parenthesis. Si
NMR (CDCl
4
3
.4 Hz, 2H), 2.38 (t, J¼7.3 Hz, 2H), 1.68 (m, 2H), 0.70 (m, 2H), 0.16 (s,
3
):
d
21.2 (11), 13.2 (dichloroethylsilane), 5.33 (10), ꢁ0.33
1
3
H). C NMR (CDCl
3
):
d
180.61, 136.59, 133.57, 37.85, 19.54, 13.98,
ꢁ12.26. HRMS (ESI) Calcd for C Si:
(12). At 24 h the solution was analyzed again, and was found to
ꢁ
5.26. 29Si NMR (CDCl
83.0847 (MꢁH ), found: 183.0836.
3
):
d
9
H
15
O
2
29
contain 6 resonances. The two additional peaks were found by Si
NMR (CDCl ):
36.5 (dichlorodiethylsilane), ꢁ13.7 (13).
ꢁ
1
3
d
4
0
.3.3. 0.5-Generation Y dendrimer (7). Tetravinylsilane (1 mmol,
.167 mL, 0.134 g) was dissolved in anhydrous THF (10 mL). Kar-
4
.4.3. Redistribution of 2 with various dichlorosilanes. For all
dichlorosilane redistribution tests an NMR tube CDCl (0.380 mL)
and 6 (0.050 mL) was prepared. Then, the individual dichlor-
osilanes (0.050 mL) were injected; one per NMR tube, and the NMR
tube was heated for 3 h at 40 C. Full multinuclear NMR was ac-
quired. Silicon NME was most useful and a full Si analysis appears
in Fig. S1 of the Supplementary data.
3
stedt catalyst solution (0.010 mL, 2.1% Pt) was added and the mix-
ture was stirred for 2 min. Then chlorodimethylsilane (6 mmol,
0
.666 mL, 0.568 g) was injected into the flask, which was stirred for
ꢀ
15 min while the mixture was heated to reflux from the heat of
29
reaction. When the exotherm subsided, the flask was submerged
into a 40 C bath for 3 h. All volatiles were evacuated leaving
ꢀ
a white semi-solid. No further purification was attempted with the
1
Acknowledgements
reactive chlorosilane intermediates (0.51 g) H NMR (CDCl
3
):
d 0.66
13
(
m, 8H), 0.57 (m, 8H), 0.40 (s, 24H). C NMR (CDCl
3
):
d
11.4, 2.2, 1.2.
2
9
We thank the U.S. Department of Energy, grant DE-FG02-
Si NMR (CDCl
3
): d 33.1.
03ER15457, for support for CMD though the Institute for Catalysis
in Energy Processes (ICEP) at Northwestern University, and grant
DE-FG02-01ER15184 for support of MNM. We thank the Integrated
Molecular Structure Characterization Education and Research
Center (IMSERC) at Northwestern University for NMR facilities.
4
.3.4. First-generation
Y
dendrimer (8). Product7 (0.8 mmol)
remaining in the reaction flask was dissolved toluene (10 mL), and
then pyridine (5.5 mmol, 0.450 mL, 0.44 g) was added, followed by
16 (3.6 mmol, 0.670 g). The mixture was stirred for 1 h, and then
chlorotrimethylsilane (1 mmol, 0.127 mL, 0.108 g) was injected and
the reaction proceeded for another 15 min. The pyridinium chloride
salt was air-free filtered and washed twice with toluene (two por-
tions, 10 mL). All volatiles were evacuated. H NMR indicated cap-
ped-16 was present. The product was purified further by addition of
Supplementary data
1
The contents of Supplementary data include the following: (A)
2
9
Si NMR of ligand redistribution of first-generation V Type den-
toluene (25 mL) and evacuation to remove residual capped-16.
drimer (2) with various dichlorosialnes, (B) third-generation V Type
dendrimer (6) figure and (C) FTIR of first-(2), second-(4), and third-
generation (6) V Type dendrimers. Supplementary data related to
this article can be found online at doi:10.1016/j.tet.2011.07.068.
1
Product 8 was recovered as clear oil (0.95 g) H NMR (CDCl
3
):
d
6.34
(
dd, J¼19.5, 14.6 Hz, 8H) 6.22 (dd, J¼14.6 Hz. J¼4.1 Hz, 8H), 5.92 (dd,
J¼19.5, 4.1 Hz, 8H), 2.54 (t, J¼7.6 Hz, 8H), 1.84 (m, 8H), 0.87 (m, 8H),
13
0
.79 (m, 8H), 0.67 (m, 8H), 0.47 (s, 24H), 0.35 (s, 12H). C NMR
2
9
(
CDCl
3
):
d
174.3, 136.7, 133.5, 39.5, 19.7, 13.9, 8.2, 1.8, ꢁ2.2, ꢁ5.2. Si
): Si : C,
23.2, 10.4, ꢁ12.8. Anal. Calcd for C48
4.53; H, 9.54, found: C, 57.70; H, 9.29.
References and notes
NMR (CDCl
5
3
d
H
100
O
8
9
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4
494e4499.
2
. Aulenta, F.; Drew, M. G. B.; Foster, A.; Hayes, W.; Rannard, S.; Thornthwaite, D.
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