A convergent route to poly(phenyl ketone ether) dendrons

Article abstract of DOI:10.1016/j.tet.2006.08.012

A series of poly(phenyl ketone) dendrons have been constructed using a convergent strategy. An aryl fluoro-substituent is deactivated towards nucleophilic substitution by protection of a para-ketone as an acetal. This allows coupling to an activated aryl

Full text of DOI:10.1016/j.tet.2006.08.012

Tetrahedron 62 (2006) 10208–10214
A convergent route to poly(phenyl ketone ether) dendrons
*
A. R. Lister and S. C. Moratti
Melville Laboratory for Polymer Synthesis, Chemistry Department, Lensfield Rd, Cambridge, CB2 1EW, UK
Received 27 April 2006; revised 10 July 2006; accepted 3 August 2006
Available online 1 September 2006
Abstract—A series of poly(phenyl ketone) dendrons have been constructed using a convergent strategy. An aryl fluoro-substituent is deac-
tivated towards nucleophilic substitution by protection of a para-ketone as an acetal. This allows coupling to an activated aryl fluoride.
Subsequent deprotection of the acetyl group then activates the first fluoro-substituent and allows the next generation of the dendron to be
added. The synthesis of higher generations is complicated by a scrambling reaction, which lowers the yields.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
defect in the dendrimer makes only a small difference to
its properties.
Ever since their realisation in the 1980s,1 dendrimers have
been widely studied due to their unique properties.2 The
exterior or interior can be decorated with functional groups
for applications such as encapsulation,3 light harvesting,4
catalysis5 or electroluminescence.6 Most dendrimers are
constructed using flexible linkers, as their chemistry and
processing tend to be easier. However, in certain applications
where structural integrity is important, rigid branches may
prove important. Examples of rigid dendrimers include those
based on branched phenylenes7 and phenylacetylenes.8
While dendrimers have been the focus of research in the
past, more recently dendrons have proved their importance
in their own right as solubilising and rigidifying modifiers
for polymers.9
The convergent method on the other hand differs in the fact
that the synthesis starts from the periphery monomer units
and works inwards to form dendrons or ‘wedges’. These
wedges (once the desired size is obtained) can be attached
to a polyfunctional core to form the dendrimer. The conver-
gent method has the advantage in the fact that in each step
there are only two reactions (i.e., two monomers/dendrons
in the nth generation couple to the appropriate functionality
of the monomer unit in the (nꢀ1)th generation) and the num-
ber of reaction sites does not increase with increasing size of
the dendrimer, unlike in the divergent approach. However,
if the dendrons become too big, reactivity may become
impaired due to the large amount of crowding that develops
near the focal point.
There are two distinct routes for dendrimer/dendron synthe-
sis, namely the divergent or convergent step-wise growth
methods. The divergent method of dendrimer synthesis
involves the build up of successive layers of protected, poly-
functional monomers starting from a central core. Several
addition/activating steps are carried out until the desired
dendrimer size is obtained. An increasing number of chain
end monomers at the periphery is produced as the dendrimer
is built up. An example of this is the synthesis of poly(amido-
amine) PAMAM Starburst dendrimers,1c,d where ammonia
acts as the core molecule. As successive generations are built
up it gets increasingly difficult to obtain high yielding reac-
tions and the maximum size of the dendrimer is limited due
to the level of steric crowding at the surface. Another prob-
lem is in the purification at each generation, as any single
We were interested in the possible use of dendrimers and
dendrons as high glass transition temperature (Tg) cross-
linkers and polymer modifiers. For these purposes, the exte-
rior needed to be decorated with (protected) phenolic
groups, and the branching linkers needed to be thermally
and oxidatively stable. The high Tg was hoped to be afforded
by the use of rigid branching units. While the Tg of un-cross-
linked dendrimers seems to be determined by the outer sur-
face functionality as much by the nature of the branching
linkages,10 no studies have been made on cross-linked mate-
rials. The diaryl ketone linkage was chosen as being suitable
as the Tg of linear poly(phenyl ketones) ranges from 150 to
220 ꢁC.11 There are two main routes known for the synthesis
of polyphenyl ketone dendrimers. The first was a convergent
route, which used an oxidative step to activate the fluoro-
phenyl group towards further nucleophilic substitution
(Scheme 1a).12 This was ruled out in the present case for
two reasons. The branching units in our case were ethers,
which may activate the phenyl unit towards oxidation. As
Keywords: Dendron; Dendrimer; Aromatic nucleophilic substitution;
Acetal.
* Corresponding author. Tel.: +44 1223 740244; e-mail: scm1001@cam.
ac.uk
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.08.012

A. R. Lister, S. C. Moratti / Tetrahedron 62 (2006) 10208–10214
10209
O
C
O
C
ROH
OR
O
CH2
F
F
(a)
O
F
R
OMe
O
R
OH
(b)
Scheme 1.
well, the oxidation may prove less selective or lower yield-
ing as the size of the dendrimer increases. The second di-
vergent method used the deprotection of methoxy phenyl
ethers with BBr3 or AlCl3 to expose new phenoxy-groups
(Scheme 1b).13
the remainder being the starting material (Scheme 2). The
unprotected phenolic group did not appear to interfere in
the reaction. The protected ketone 2 was then reacted with
4-fluorophenyl phenyl ketone 3 using sodium carbonate as
base at 160 ꢁC to give 6 in 81% isolated yield without any
apparent side products (Scheme 2). The reaction appeared
clean, with no other products isolated. Gratifyingly, the
cyclic acetal showed no signs of instability at those temper-
atures and conditions. Deprotection was cleanly performed
by heating in acetone in the presence of an acid catalyst to
give diketone 4 in 93% yield from 3. Our work would
seem to be the first to directly protect an activated aryl-
fluorine group via the use of acetal protection chemistry.
Dendrimers normally use a protection–deprotection scheme
in order to selectively couple units together. The most obvi-
ous protection chemistry for the aromatic ketones would
appear to be the use of cyclic acetals, which can be cleanly
deprotected under mildly acidic conditions. Cyclic acetals
have been used to protect fluorophenyl ketones in the synthe-
sis of pharmaceutical derivatives, though in these instances
the acetal groups were used to protect the ketone than to con-
trol the activation of the fluoro-substituent as here.14 They
have also been used to functionalise the carbonyl groups
of poly(phenyl ketones) to give improved solubility over
the parent polymer.15 In that particular case, though, the ace-
tal groups were added after the nucleophilic polymerisation
step.
The key dihydroxyketone 6 was prepared in two steps from
the reaction of 4-fluorophenyl magnesium chloride with 3,5-
dimethoxybenzoyl chloride to give 5, followed by deprotec-
tion of the methoxy groups with BBr3 (Scheme 3). The diol 6
was then protected with 1,2-bis(trimethylsiloxy)ethane. The
resulting product 7, isolated in 70% yield, proved only mod-
erately stable and decomposed upon standing after a week.
Undoubtedly, the presence of the mildly acidic phenolic pro-
tons was catalysing the attack on the acetal functionality.
However, 7 could be kept indefinitely in solution (in THF)
if stored over sodium carbonate. In practise, the compound
was used immediately after preparation and purification.
2. Results
We were unsure whether a simple acetal could withstand the
high temperatures and polar solvents usually used in aro-
matic nucleophilic substitutions. To this end, some model
chemistry was undertaken in order to prove the concept.
Formation of an acetal of 4-hydroxyphenyl ketone 1 was
attempted under standard conditions (ethylene glycol, acid,
azeotropic removal of water), but even after 5 days, only
starting material could be recovered. It was possibly due to
that the phenolic group was interfering in the reaction.
Diaryl ketones appear difficult to protect with acetal groups
at the best of times and prolonged reaction times (5 days
or more) have often been employed.15 A milder literature
procedure to protect aromatic ketones involving 1,2-bis(tri-
methylsiloxy)ethane was then tried.16 This reaction, which
requires the use of a catalyst, trimethylsilyl trifluoromethane-
sulfonate, went in reasonable yield (71%) after only 3 h,
The reaction between 4-fluoro-30,50-dihydroxybenzophe-
none and 7 proceeded in 73% yield to give a waxy amor-
phous solid 8. Sodium carbonate was used as a base, as it
has been reported that the use of potassium carbonate can
catalyse transetherification reactions in similar systems.17
This is because the bi-product, potassium fluoride, is soluble
in DMSO solvent and can attack the existing diphenyl
ketone ether structures, whereas sodium fluoride is insolu-
ble. While this is of little consequence when producing poly-
mers, in the present case any transetherification will produce
scrambling of the dendrimer leading to defects in the struc-
tures. We looked at DMF as an alternative solvent. However,
at high temperatures needed for the coupling, we found some
O
O
O
O
O
O
OH
O
OH
1
2
3
O
O
O
4
Scheme 2.

10210
A. R. Lister, S. C. Moratti / Tetrahedron 62 (2006) 10208–10214
OH
OH
OMe
OMe
O
O
F
MgBr
O
BBr3
F
F
Cl
OMe
OMe
5
6
19
OMe
17
16
15
13 14
O
OH
18
TMSO
OTMS
12
11
10
5
O
O
F
OMe
20
TMSOTf
Na2CO3, DMSO
OH
O
3
4
8
2
7
6
R
5
1
7
8
9
R = -OCH2CH2O-
9
F
R = O
O
OMe
OMe
O
Scheme 3. Synthesis of generation one dendron 9.
O
with only one product seen on TLC analysis and isolated.
Compound 8 was deprotected cleanly to give the first gener-
ation product 9. Coupling of 9 with 7 under identical condi-
tions as before gave the protected second generation wedge
10 in a reduced yield of 48% (Fig. 1). Unlike previous cou-
plings, several other compounds could be seen under TLC
analysis, suggesting that the reaction was not quite as clean
as hoped. Deprotection as before gave 11 in 83% yield as an
amorphous white solid. While the deprotection was very
clean by TLC analysis, some of the compounds appeared
to irreversibly bind to the silica column, perhaps accounting
for the less than quantitative yields.
28
25
21
20
22
24
26
OMe
23
27
19
O
16 17
15
OMe
OMe
O
18
14
12 13
11
10
O
OMe
OMe
O
2
3
7 8
R
5
O
O
1
6
4
9
F
O
29
O
O
10 R = -OCH2CH2O-
Attempted preparation of the third generation wedge pro-
duced a complex mixture that couldn’t be purified further.
It was obvious that side reactions were competing with the
desired coupling reactions. In order to determine the possi-
ble cause, a model study was performed. Coupling of
4-hydroxybenzophenonewith1,underconditionsusedprevi-
ously, gave an isolated yield of 87% of the expected product
12, along with 3% of the side-product 13. The side-product
was clearly being produced by the attack of phenoxide on
the product (Scheme 4). Transetherification in benzophenone
derivatives has been noted before,17 and we were unable to
find any different conditions (temperature, solvents or
base) to eliminate the formation of this side-product. It ap-
pears that the rate difference in the nucleophilic aromatic
substitution between an aryl fluoride and aryl phenyl ether
OMe
OMe
11 R = O
O
OMe
O
Figure 1. Structure and atom numbering of dendrons 10 and 11.
substitution of fluoride with dimethylamine had occurred.
This side-product, probably arose via decomposition of the
solvent under the basic conditions.
The NMR of 8 showed that the acetal ring survived during
the reaction and work-up. Again, the reaction appeared clean
OCH3
O
O
Na2CO3
OH
+
F
DMSO
OCH3
OCH3
12
O
O
O
O
13
O
O
87%
OCH3
3%
Scheme 4. Model coupling reaction.

A. R. Lister, S. C. Moratti / Tetrahedron 62 (2006) 10208–10214
10211
4. Experimental
4.1. General
1H NMR spectra were recorded using Bruker DPX-250
(250 MHz), DPX-400 (400 MHz) and DPX-500 (500 MHz)
using the indicated deuterated solvent. Chemical shifts
(d in parts per million) are quoted relative to residual proton
signals in chloroform where d (CHCl3)¼7.26. Signal multi-
plets are quoted as s (singlet), d (doublet), t (triplet), q
(quartet), m (multiplet) and br (broad). Infrared spectra
were recorded on a Nicolet 510 FT-IR spectrometer. The
samples were prepared as KBr discs or as thin films on
NaCl plates as an oil. Microanalysis was performed by the
University Chemical Laboratory Microanalytical Depart-
ment. Melting points were determined using a Gallenkamp
melting point apparatus and are not corrected. Flash chroma-
tography was carried out on Merck Silica Gel 60. Thin layer
chromatography (TLC) was carried out on a pre-coated
0.2 mm Merck 60 F254 silica plates, visualised by either
UV light (366 nm) or potassium permanganate oxidation.
Size exclusion chromatography was carried out using 3
Polymer Laboratories PL Gel mixed C (cross-linked poly-
styrene/divinylbenzene) columns, chloroform solvent, flow
rate 1 mL/min and at 30 ꢁC.
Figure 2. Size exclusion chromatographs of dendrons 9 and 11.
may be fairly insensitive to conditions. Three percent trans-
etherification is of minor consequence in the formation of
lower generation dendrimers. However, by the time a genera-
tion three product is required, there are six times more
potentially reactive aryl ether sites than fluoride sites in the
starting material. Added to this is the strong possibility that
the terminal fluoride group may have lower reactivity than
expected due to steric crowding at the apex of the dendron.
The net result appears to be the scrambling of dendrimeric
structure at high generation, which appears to be a limitation
in the use of a nucleophilic route to higher poly(phenyl ether)
structures at present.
4.1.1. 4-(2-Phenyl-[1,3]dioxolan-2-yl)-phenol (2). To a
solution of 4-hydroxybenzophenone 1 (0.60 g, 3.0 mmol)
in dry DCM (15 mL), at 0 ꢁC under nitrogen, was added
1,2-bis(trimethylsilyloxy)ethane (1.40 mL, 6.1 mmol). The
mixture was left for 30 min under nitrogen and then tri-
methylsilyl trifluoromethanesulfonate (0.06 mL, 0.3 mmol)
was added under nitrogen. After 30 min the temperature
was raised to room temperature for 5 h. Pyridine (0.1 mL)
was added to the mixture and then it was placed into water
(40 mL) and extracted with ethyl acetate (3ꢂ30 mL). The
combined extracts were then dried over magnesium sulfate,
filtered and concentrated in vacuo. Column chromatography
on silica gel, using 82:18 hexane/ethyl acetate yielded 0.52 g
(71%) of a white solid, 2; Rf (hexane/ethyl acetate 1:1) 0.85;
mp 107–109 ꢁC; IR (KBr) 3100–3000, 2900, 1590, 1555,
The purity of the generations one and two wedges was
1
checked for any scrambling. The H and 13C NMR spectra
of both products were very clean, and all the carbons could
be accounted for, with no extra peaks. The carbon and proton
spectra were fully assigned by use of model compounds and
peak intensities. Gel permeation chromatography of the
generations one and two structures showed a monodisperse
product (polydispersity<1.05) (Fig. 2), and mass spectral
analysis (ESI) showed no higher molecular weight products.
The dendrimers were all amorphous, waxy materials,
perhaps suggesting a low Tg for the un-cross-linked material.
DSC measurements did not reveal an obvious glass tran-
sition point, perhaps due to the variety of the structural
elements present.
1
1500, 1250, 1180 cmꢀ1; H NMR (400 MHz) d (CDCl3)
3
7.49 (d, 2H, H-3, JHH¼8.0 Hz), 7.37–7.25 (m, 5H,
3
aromatic), 6.74 (d, 2H, H-8, JHH¼9.0 Hz), 4.93 (s, 1H,
OH), 4.04 (m, 4H, H-10); m/z (ESI) 265.08 [M+Na+.
C15H14O3Na requires M+Na, 265.08406]; m/z (ESI) 265.1
(M+Na+, 100%), 243.1 (23%); found C, 74.0%; H, 5.8%.
C15H14O3 requires C, 74.4%; H, 5.8%.
3. Conclusions
Protection of an aryl fluoride towards nucleophilic substitu-
tion can be achieved via acetylisation of a para-ketone
substituent. The best reagent for the protection was found
to be trimethylsilyl trifluoromethanesulfonate. Deprotection
can be achieved under mild acidic conditions to activate the
fluoro-group. This protection–deprotection strategy allows
the formation of phenyl ketone denritic wedges and possibly
dendrimers to be constructed in a convergent fashion. A
generation two dendritic wedge was ultimately constructed.
This method works well for lower generations, but trans-
etherification produces scrambling at higher generation
that limits the utility of this method at this time for larger
structures until more selective reaction conditions are found.
4.1.2. Phenyl-4-{[4-(2-phenyl-[1,3]dioxolan-2-yl)-phen-
oxy]-phenyl}-methanone (3). To a solution of compound
2 (0.50 g, 2.1 mmol) and 4-fluorobenzophenone (0.46 g,
2.1 mmol) in dry DMSO (20 mL) was added Na2CO3
(0.22 g, 2.1 mmol). The mixture was heated to 160 ꢁC for
24 h and then cooled to room temperature. Water (40 mL)
was then added and the mixture was extracted with ethyl
acetate (3ꢂ30 mL). The combined extracts were then dried
over magnesium sulfate, filtered and concentrated in vacuo.
Recrystallisation from hexane/ether yielded 0.72 g (84%) of
a white solid, 3; Rf (hexane/ethyl acetate 1:1) 0.69; mp 119–
121 ꢁC; IR (KBr) 3050, 2900, 1660, 1590, 1310, 1250, 1180,
1
1080 cmꢀ1; H NMR (400 MHz) d (CDCl3) 7.79 (d, 2H,

10212
A. R. Lister, S. C. Moratti / Tetrahedron 62 (2006) 10208–10214
3
3
H-16, JHH¼7.0 Hz), 7.76 (d, 2H, H-12, JHH¼7.0 Hz),
temperature. The solvent was evaporated and column chro-
matography on silica gel using 73:27 hexane/ethyl acetate
yielded 0.43 g (72%) of a waxy solid, 8; Rf (hexane/ethyl
acetate 1:1) 0.60; IR (KBr) 2900, 1725, 1600, 1505, 1480,
3
7.58–7.50 (m, 4H, aromatic), 7.45 (t, 2H, H-2, JHH
8.0 Hz), 7.36–7.27 (m, 4H, aromatic), 7.04 (d, 2H, H-8,
¼
3JHH¼7.0 Hz), 7.01 (d, 2H, H-11, JHH¼7.0 Hz), 4.07 (m,
3
4H, H-19, H-20); 13C NMR (100 MHz) d (CDCl3) 195.5,
161.3, 155.4, 141.9, 138.4, 137.9, 132.4, 132.1, 132.0,
129.8, 128.2, 128.2, 128.1, 126.1, 119.6, 117.3, 109.1, 64.9;
m/z (EI) 422.15206 [M+. C28H22O4 requires M,
422.15181]; m/z (EI) 422.2 (M+, 40%), 345.1 (100%),
149.1 (57%), 68.9 (38%); found C, 79.6%; H, 5.3%.
C28H22O4 requires C, 79.4%; H, 5.3%.
1380, 1160, 1100 cmꢀ1; H NMR (400 MHz) d (CDCl3)
1
3
7.81 (d, 4H, H-12, JHH¼8.8 Hz), 7.45 (m, 2H, H-3),
7.09–6.08 (m, 8H, H-7, H-2, H-11), 6.87 (d, 4H, H-16,
4
3JHH¼2.3 Hz), 6.71 (t, 1H, H-9, JHH¼2.3 Hz), 6.65 (t,
4
2H, H-18, JHH¼2.3 Hz), 4.05 (m, 4H, H-20), 3.82 (s,
12H, H-19); 13C NMR (100 MHz) d (CDCl3) 195.0 (C14),
162.6 (d, JCF¼246 Hz, C1), 160.6 (C17, C10), 156.9 (C8),
146.4 (C6), 137.8 (C4), 132.5 (C12), 132.5 (C13), 127.8
(d, JCF¼9 Hz, C3), 117.9 (C11), 115.3 (d, JCF¼21 Hz,
C2), 113.4 (C7), 110.8 (C9), 108.3 (C5), 107.7 (C16),
104.5 (C18), 65.1 (C20), 55.6 (C19); m/z (ESI) 779.22780
[M+Na+. C45H37O10F requires M+Na, 779.22685]; m/z
(ESI) 779.23 (M+Na+, 100%); found C, 71.9%; H, 4.8%.
C45H37O10F requires C, 71.5%; H, 4.9%.
4.1.3. Bis-(4-benzoylphenyl) ether (4). To a solution of 3
(0.50 g, 1.2 mmol) in acetone (15 mL) was added p-toluene-
sulfonic acid (0.33 g, 1.2 mmol). The mixture was heated at
50 ꢁC for 3 h and then placed in water (30 mL). The mixture
was then extracted with ethyl acetate (3ꢂ30 mL). The com-
bined extracts were then dried over magnesium sulfate,
filtered and concentrated in vacuo. Recrystallisation from
ethanol yielded 0.42 g (93%) of a white solid, 4; Rf
(hexane/ethyl acetate 1:1) 0.72; mp 162–164 ꢁC (lit.18 mp
163–165 ꢁC); IR (KBr) 3030, 1650, 1600, 1500, 1320,
4.1.6. Deprotected first generation poly(ether ketone)
dendron (9). To the methoxy terminated poly(ether ketone)
dendron 8 (0.27 g, 0.35 mmol) in acetone (10 mL) was added
p-toluenesulfonic acid (0.2 g). The mixture was heated at
50 ꢁC for 3 h and then placed in water (30 mL). The mixture
was then extracted with ethyl acetate (3ꢂ30 mL). The com-
bined extracts were then dried over magnesium sulfate, fil-
tered and concentrated in vacuo. Column chromatography
on silica gel using 75:25 hexane/ethyl acetate yielded
0.21 g (83%) of a waxy solid, 9; Rf (hexane/ethyl acetate
1:1) 0.67; IR (KBr) 3000, 2810, 1725, 1655, 1600, 1505,
1290, 1170 cmꢀ1; H NMR (400 MHz) d (CDCl3) 7.87 (d,
1
3
3
4H, H-7, JHH¼9.0 Hz), 7.79 (d, 4H, H-3, JHH¼7.0 Hz),
3
7.58 (t, 2H, H-1, JHH¼7.5 Hz), 7.48 (t, 4H, H-2,
3JHH¼7.5 Hz), 7.14 (d, 4H, H-8, JHH¼9.0 Hz); m/z (EI)
3
378.12547 [M+. C26H18O3 requires M, 378.12559]; m/z
(EI) 378.1 (M+, 98%), 301.1 (100%), 68.9 (97%); found
C, 82.3%; H, 4.8%. C26H18O3 requires C, 82.5%; H, 4.8%.
4.1.4. 5-(2-Phenyl-[1,3]dioxolan-2-yl)-benzene-1,3-diol
(7). To
1480, 1280, 1170, 1080 cmꢀ1 1H NMR (400 MHz)
;
a
solution of 4-fluoro-30,50-dihydroxybenzo-
d (CDCl3) 7.85 (m, 6H, H-3, H-12), 7.27 (d, 2H, H-7,
4JHH¼2.0 Hz), 7.16 (t, 2H, H-2, JHH¼3JHF¼8.5 Hz), 7.09
phenone10c 6 (1.10 g, 4.7 mmol) in dry ether (15 mL), at
0 ꢁC under nitrogen, was added 1,2-bis(trimethylsilyloxy)-
ethane (1.40 mL, 6.1 mmol). The mixture was left for
30 min under nitrogen and then trimethylsilyl trifluoro-
methanesulfonate (0.06 mL, 0.3 mmol) and trifluoroacetic
acid (two drops) were added. After 30 min, the temperature
was raised to room temperature for 5 h. Pyridine (0.1 mL) was
added to the mixture and, after 30 min, water (40 mL) was
added. The mixture was extracted with ethyl acetate (3ꢂ
30 mL). The combined extracts were then dried over magne-
sium sulfate, filtered and concentrated in vacuo. Column
chromatography on silica gel using 60:40 hexane/ethyl ace-
tate yielded a waxy solid. The waxy solid was stirred in
DCM where upon a precipitate was formed. The precipitate
was filtered and the filtrate was concentrated in vacuo to
yield 0.93 g (70%) of a waxy solid, 7; Rf (hexane/ethyl ace-
tate 1:1) 0.40; IR (KBr) 3100–3000, 2900, 1720, 1600, 1650,
3
(d, 4H, H-11, 3JHH¼8.5 Hz), 7.03 (t, 1H, H-9, 4JHH¼2.0 Hz),
4
6.87 (d, 4H, H-16, JHH¼2.5 Hz), 6.65 (t, 2H, H-18,
4JHH¼2.5 Hz), 3.82 (s, 12H, H-19); 13C NMR (100 MHz)
d (CDCl3) 194.9 (C14), 193.2 (C5), 165.5 (d, JCF¼254 Hz,
C1), 160.6 (C17), 160.0 (C8), 157.4 (C10), 140.7 (C6),
139.5 (C15), 133.0 (C13), 132.9 (d, JCF¼3 Hz, C4), 132.7
(d, JCF¼9 Hz, C3), 132.6 (C12), 117.9 (C11), 116.2 (C7),
115.7 (d, JCF¼24 Hz, C2), 114.6 (C9), 107.7 (C16), 104.5
(C18), 55.6 (C19); m/z (EI) 735.20008 [M+Na+.
C43H33O9F requires M+Na, 735.20063]; m/z (ESI) 735.20
(M+Na+, 30%), 306.1 (100%); found C, 72.7%; H, 5.2%.
C43H33O9F requires C, 72.5%; H, 5.0%.
4.1.7. Second generation protected poly(ether ketone)
dendron (10). Protected dendron 9 (0.20 g, 0.275 mmol)
and diol 7 (0.038 g, 0.14 mmol) were dissolved in dry
DMSO (7 mL) and Na2CO3 (0.12 g) was added. The mixture
was heated to 160 ꢁC for 24 h and then cooled to room tem-
perature. Column chromatography on silica gel using 55:45
hexane/ethyl acetate yielded 0.11 g (48%) of a waxy solid,
10; Rf (hexane/ethyl acetate 1:1) 0.52; IR (KBr) 3000,
2900, 1725, 1650, 1600, 1505, 1480, 1380, 1160, 1100,
1080 cmꢀ1; 1H NMR (400 MHz) d (CDCl3) 7.87–7.79 (2d,
1510, 1500, 1420, 1225, 1180 cmꢀ1; H NMR (400 MHz)
1
3
4
d (CDCl3) 7.45 (dd, 2H, H-3, JHH¼9.0 Hz, JHF¼9.0 Hz),
6.98 (t, 2H, H-2, JHH¼4JHF¼9.0 Hz), 6.54 (d, 2H,
3
H-7, 4JHH¼2.5 Hz), 6.26 (d, 1H, H-9, 4JHH¼2.5 Hz), 5.00–
4.85 (s, 2H, OH), 4.04 (m, 4H, H-10, H-11); m/z
(EI) 276.1 (M+, 38%), 181.1 (45%), 167.1 (54%), 123.0
(54%), 95 (71%), 68.9 (100%); found C, 65.3%; H, 4.1%.
C15H13O4F requires C, 65.2%; H, 4.7%.
3
3
12H, H-12, H-21, JHH¼8.5 Hz), 7.43 (t, 2H, H-2, JHH
¼
3JHF¼9.0 Hz), 7.26 (m, 4H, aromatic), 7.15–6.95 (m, 16H,
3
4.1.5. First generation protected poly(ether ketone) den-
dron (8). 4-Fluoro-30,50-dimethoxybenzophenone18 5 (0.44 g,
1.6 mmol) and 7 (0.11 g, 0.8 mmol) were dissolved in dry
DMSO (10 mL) and Na2CO3 (0.20 g) was added. The mix-
ture was heated to 160 ꢁC for 24 h and then cooled to room
aromatic), 6.87 (d, 8H, H-25, JHH¼2.0 Hz), 6.70 (m, 3H,
H-18, H-9), 6.65 (t, 4H, H-27, 4JHH¼2.0 Hz), 4.03 (m, 4H,
H-29, H-30), 3.80, (s, 24H, H-28); 13C NMR (100 MHz)
d (CDCl3) 194.9 (C23), 193.3 (C14), 164.6 (d, JC–F
151 Hz, C1), 161.4 (C10), 161.1 (C26), 160.6 (C19), 157.2
¼

A. R. Lister, S. C. Moratti / Tetrahedron 62 (2006) 10208–10214
10213
(C17), 156.7 (C8), 146.5 (C6), 141.0 (C15), 139.4 (C24),
132.9 (C22), 132.6 (C21), 132.5 (C12), 131.9 (C4),
131.5 (C13), 127.8 (d, JCF¼8 Hz, C3), 118.0 (C20),
117.6 (C11), 116.3 (C16), 115.2 (d, JCF¼21 Hz, C2),
114.4 (C7), 113.6 (C18), 111.1 (C9), 108.3 (C5), 107.7
(C25), 104.5 (C27), 65.1 (C29), 55.6 (C28); found C,
73.2%; H, 4.4%. C101H77O22F requires C, 73.0%; H,
4.7%.
Column chromatography using 85:15 hexane/ethyl acetate
and crystallisation from ether/hexane yielded 0.009 g (3%)
of a white solid, 4.
Acknowledgements
We gratefully acknowledge Qinetic Ltd for a Studentship
(A.R.L.).
References and notes
4.1.8. Second generation deprotected poly(ether ketone)
dendron (11). To the methoxy terminated poly(ether
ketone) dendron 10 (0.11 g, 0.056 mmol) in acetone (10 mL)
was added p-toluenesulfonic acid (0.1 g). The mixture was
heated at 50 ꢁC for 3 h and then placed in water (20 mL).
The mixture was then extracted with ethyl acetate (3ꢂ
20 mL). The combined extracts were then dried over magne-
sium sulfate, filtered and concentrated in vacuo. Column
chromatography on silica gel using 57:43 hexane/ethyl ace-
tate yielded 0.09 g (80%) of a waxy solid, 11; Rf (hexane/
ethyl acetate 1:1) 0.54; IR (KBr) 2900, 1725, 1700, 1690,
1650, 1600, 1505, 1480, 1280, 1235, 1155, 1080 cmꢀ1; 1H
NMR (400 MHz) d (CDCl3) 7.85 (m, 14H, H-3, H-12,
H-21), 7.27–7.23 (m, 7H, aromatic), 7.15–7.00 (m, 16H,
1. (a) Denkewalter, R. G.; Kolc, J. F.; Lukasavage, W. J. U.S.
Patent 4,410,688, 1983; (b) Newkombe, G. R.; Yao, Z.;
Baker, G. R.; Gupta, V. K. J. Org. Chem. 1985, 50, 2003–
2004; (c) Tomalia, D. A. B.; Dewald, J.; Hall, M.; Kallos, G.;
Martin, S.; Roeck, J.; Ryder, J.; Smith, P. Polym. J. 1985, 17,
117–132; (d) Tomalia, D. A. B.; Baker, H.; Dewald, J.; Hall,
M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P.
Macromolecules 1986, 19, 2466–2468; (e) Padias, A. B.;
Hall, H. K.; Tomalia, D. A.; McConnell, J. R. J. Org. Chem.
1987, 52, 5305–5312.
€
2. (a) Newkome, G. R.; Moorefield, C. N.; Vogtle, F. Dendrimers
and Dendrons; Concepts, Synthesis and Applications; Wiley-
VCH: Weinheim, 2001; (b) Topics in Current Chemistry,
3
aromatic), 6.87 (d, 8H, H-25, JHH¼2.3 Hz), 6.64 (t, 4H,
4
H-27, JHH¼2.3 Hz), 3.80 (s, 24H, H-28); 13C NMR
Vol. 197, Dendrimers; Vogtle, F., Ed.; Springer: Berlin, 1998;
€
and Vol. 210, Dendrimers II, Springer: Berlin, 2000; (c) Den-
(100 MHz) d (CDCl3) 194.9 (C23), 193.2 (C14), 193.0
(C5), 160.6 (C26), 160.5 (C10), 160.1 (C19), 157.3 (C17),
157.1 (C8), 140.9 (C15), 140.8 (C6), 139.5 (C24), 133.0
(C22), 132.7 (C21+C12+C3), 132.6 (C4), 132.1 (C13),
118.0 (C11), 117.9 (C20), 116.5 (C7), 116.4 (C16), 115.7
(d, JCF¼18 Hz), 114.8 (C9), 114.5 (C18), 107.7 (C25),
104.5 (C27), 55.6 (C28); SEC (THF) Mw 1210, PD 1.05;
found C, 73.0%; H, 5.3%. C99H73O8F requires C, 73.4%;
H, 4.8%.
ꢀ
drimers and Other Dendritic Polymers; Frechet, J. M. J.,
Donald, A., Tomalia, D. A., Eds.; Wiley: Chichester, UK,
2001.
3. Jansen, J. F. G. A.; De Brabander Vandenberg, E. M. M.;
Meijer, E. W. Science 1994, 266, 1226–1229.
4. (a) Stewart, G. M.; Fox, M. A. J. Am. Chem. Soc. 1996, 118,
4354–4360; (b) Balzani, V.; Campagna, S.; Denti, G.; Juris,
A.; Serroni, S.; Venturi, M. Coord. Chem. Rev. 1994, 132,
1–13.
4.1.9. {4-[4-(3,5-Dimethoxy-benzoyl)-phenoxy]-phenyl}-
phenyl-methanone (12). To a solution of 4-fluoro-30,50-di-
methoxybenzophenone 5 (0.20 g, 0.7 mmol) and 4-hydroxy-
benzophenone (0.15 g, 0.8 mmol) in anhydrous DMSO
(20 mL) was added Na2CO3 (0.81 g, 0.8 mmol). The mix-
ture was heated to 160 ꢁC under nitrogen for 24 h and then
cooled to room temperature. The mixture was then added
to water (40 mL) and extracted with ethyl acetate
(3ꢂ40 mL). The combined extracts were then dried over
magnesium sulfate, filtered and concentrated in vacuo. Col-
umn chromatography on silica gel using 90:10 hexane/ethyl
acetate yielded 0.30 g (89%) of product as a waxy solid, 12;
Rf (hexane/ethyl acetate 1:1) 0.82; IR (KBr) 2950, 2360,
5. (a) Evans, D. J.; Kanagasooriam, A.; Williams, A.; Pryce, R. J.
J. Mol. Catal. 1993, 85, 21–32; (b) Brunner, H.; Altmann, S.
Chem. Ber. 1994, 127, 2285–2296.
6. Wang, P. W.; Liu, Y. J.; Devadoss, C.; Bharathi, P.; Moore, J. S.
Adv. Mater. 1996, 8, 237–241.
7. (a) Morgenroth, F.; Ruether, E.; Mullen, K. Angew. Chem., Int.
Ed. 1997, 36, 631–634; (b) Miller, T. M.; Neenan, T. X. Chem.
Mater. 1990, 2, 346–649.
8. Xu, Z.; Moore, J. S. Acta Polym. 1994, 45, 83–87.
9. (a) Stewart, G. M.; Fox, M. A. Chem. Mater. 1998, 10, 860–
863; (b) Jakubiak, R.; Bao, Z.; Rothberg, L. Synth. Met.
ꢀ
2000, 114, 61–64; (c) Malenfant, P. R. L.; Frechet, J. M. J.
Macromolecules 2000, 33, 3634–3640; (d) Shu, L. J.;
Schafer, T.; Schluter, A. D. Macromolecules 2000, 33, 4321–
4328.
1710, 1660, 1590, 1510, 1460, 1110 cmꢀ1
;
1H NMR
3
(400 MHz) d (CDCl3) 7.87 (d, 2H, H-3, JHH¼9.0 Hz),
3
3
ꢀ
10. (a) Hawker, C. J.; Frechet, J. M. J. J. Chem. Soc., Perkin Trans.
1 1992, 2459–2469; (b) Wooley, K. L.; Hawker, C. J.; Lee, R.;
7.85 (d, 2H, H-7, JHH¼9.0 Hz), 7.78 (d, 2H, H-3, JHH
¼
3
7.0 Hz), 7.58 (t, 1H, H-1, JHH¼7.5 Hz), 7.48 (t, 2H, H-2,
3JHH¼7.5 Hz), 7.12 (m, 4H, H-8, H-11), 6.90 (d, 2H,
ꢀ
Frechet, J. M. J. Polym. J. 1994, 26, 187–197; (c) Chu, R.;
4
4
H-16, JHH¼2.5 Hz), 6.66 (t, 1H, H-18, JHH¼2.5 Hz),
3.82 (s, 6H, H-19); 13C NMR (100 MHz) d (CDCl3) 195.4,
195.0 (C5, C14), 160.6 (C17), 159.9, 159.8 (C9, C10),
139.5 (C15), 137.7 (C4), 133.5, 133.1 (C6, C13), 132.5,
132.5 (C7, C12), 132.3 (C1), 131.9, (C3), 129.8, 128.3
(C2), 118.6, 118.5 (C8, C11), 107.8 (C16), 104.5 (C18),
55.6 (C19); m/z (EI) 438.14734 [M+. C28H22O5 requires
M, 438.14673]; m/z (EI) 438.1 (30%), 301.1 (20%), 119.0
(80%), 68.8 (100%); found C, 77.1%; H, 5.7%. C28H22O5
requires C, 76.7%; H, 5.1%.
Hawker, C. J. Polym. Bull. 1993, 30, 265–272; (d) Kim,
Y. H.; Webster, O. W. Macromolecules 1992, 25, 5561–5572;
(e) Miller, T. M.; Neenan, T. X.; Zayas, R.; Blair, H. E.
J. Am. Chem. Soc. 1992, 114, 1018–1025.
11. Polymer Handbook, 4th ed.; Brandrup, J., Immergut, E. H.,
Grulke, E. A., Eds.; Wiley: New York, NY, 1999.
12. Abramov, M. A.; Shukla, R.; Amabilino, D. B.; Dehaen, W.
J. Org. Chem. 2002, 67, 1004–1007.
13. Morikawa, A.; Kakimoto, M.; Imai, Y. Macromolecules 1993,
26, 6324–6329.

10214
A. R. Lister, S. C. Moratti / Tetrahedron 62 (2006) 10208–10214
14. (a) For examples, see: Bolos, J.; Gubert, S.; Anglada, L.;
Planas, J. M.; Burgarolas, C. J. Med. Chem. 1996, 15,
2962–2970; (b) Ravina, E.; Fueyo, J.; Masaguer, C. F.;
Negreira, J.; Cid, J. Chem. Pharm. Bull. 1996, 44, 534–
541.
16. Lucas, P.; Mehdi, N. E.; Ho, H. A.; Belanger, D.; Breau, L.
Synthesis 2000, 9, 1253–1258.
17. Colquhoun, H. M.; Dudman, C. C.; Blundell, D. J.; Bunn, A.;
Macenzie, P. D.; McGrail, P. T.; Williams, D. J. Macromole-
cules 1993, 26, 107–111.
15. Kelsey, D. R.; Robeson, L. M.; Clendinning, R. A. Macro-
molecules 1987, 20, 1204–1212.
18. Fukawa, I.; Tanabe, T.; Dozona, T. J. Chem. Soc., Perkin Trans.
2 1992, 377–382.