Suzuki-Miyaura reaction catalyzed by a dendritic phosphine-palladium complex

Article abstract of DOI:10.1016/j.tet.2016.01.048

We prepared several of a new type of a dendritic ligand with a phosphine core by using tris(4-hydroxyphenyl)phosphine oxide and poly(aryl ether) dendron. In particular, when an amphiphilic dendritic phosphine-palladium complex was used as a catalyst, the aqueous media Suzuki-Miyaura reaction proceeded smoothly to provide the corresponding cross-coupling product at 50 °C. A positive dendritic effect on chemical yields was observed.

Full text of DOI:10.1016/j.tet.2016.01.048

Accepted Manuscript
Suzuki–Miyaura reaction catalyzed by a dendritic phosphine–palladium complex
Ken-ichi Fujita, Hatsuhiko Hattori
PII:
S0040-4020(16)30048-5
10.1016/j.tet.2016.01.048
TET 27455
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 26 December 2015
Revised Date: 25 January 2016
Accepted Date: 27 January 2016
Please cite this article as: Fujita K-i, Hattori H, Suzuki–Miyaura reaction catalyzed by a dendritic
phosphine–palladium complex, Tetrahedron (2016), doi: 10.1016/j.tet.2016.01.048.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Leave this area blank for abstract info.
Suzuki–Miyaura reaction catalyzed by
a dendritic phosphine–palladium complex
Ken-ichi Fujita* and Hatsuhiko Hattori

ACCEPTED MANUSCRIPT
Suzuki–Miyaura reaction catalyzed by a dendritic phosphine–palladium complex
Ken-ichi Fujita* and Hatsuhiko Hattori
National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, 1-1-1
Higashi, Tsukuba, Ibaraki 305-8565, Japan
*To whom correspondence should be addressed. E-mail: k.fujita@aist.go.jp
Keywords:
dendrimer
phosphine
catalyst
Suzuki–Miyaura reaction
Abstract: We prepared several of a new type of a dendritic ligand with a phosphine core by using
tris(4-hydroxyphenyl)phosphine oxide and poly(aryl ether) dendron. In particular, when an
amphiphilic dendritic phosphine–palladium complex was used as a catalyst, the aqueous media
Suzuki–Miyaura reaction proceeded smoothly to provide the corresponding cross-coupling product
at 50 ºC. A positive dendritic effect on chemical yields was observed.
1

ACCEPTED MANUSCRIPT
1.Introduction
Dendrimers are fascinating man-made macromolecules with their unique physical and chemical
1
properties, and have been widely used as a new class of catalyst supports. Metallodendrimers,
which have a catalytic site at their core, have received considerable attention because of their
unique selectivity and reactivity, which are caused by a specific reaction field constructed by the
2
dendron. Moreover, their solubilities and physical properties can be altered by peripheral
3
modification. For example, by the introduction of hydrophilic groups to the peripheral layer of a
hydrophobic dendritic ligand, the corresponding metal core dendrimers as catalysts can become
4
water-soluble and afford unique catalytic activity.
Figure 1 Structural formulas of 1Gn[X] and Gn[X] dendrons (n = 0–3)
Recently, several examples of a positive dendritic effect on chemical yields—that is, an enhanced
5
reactivity via an increase in the generation number of the dendrimers—have been reported by us
6
and by other groups. In our previous study, it was found that a hydrophobic dendron was effective
5
a,b
as a reaction field in aqueous media organic syntheses. In this paper, we report the synthesis of
novel phosphine core dendrimers having poly(benzyl ether) dendrons with the modification of the
7
peripheral layer 1Gn[X] (X = H, CO K, n = 0–3; Figure 1), and their application as phosphine
2
8
ligands to the Suzuki–Miyaura coupling reaction catalyzed by the phosphine–palladium complex.
In particular, by employing amphiphilic dendritic phosphine–palladium complexes having
2

ACCEPTED MANUSCRIPT
potassium carboxylate units at the peripheral layer as catalysts, an aqueous media Suzuki–Miyaura
reaction proceeded smoothly to provide the corresponding coupling product, and a positive
dendritic effect on chemical yields was observed. Suzuki–Miyaura reaction between a boronic acid
9
and an aryl or vinyl halide has become one of the most powerful carbon–carbon coupling methods.
This coupling reaction has been widely used in the synthesis of a variety of fine chemicals and
pharmaceutical products, as well as in material science. From the perspective of green chemistry,
1
0
the development of an aqueous media Suzuki–Miyaura reaction is a very attractive field, as water
1
1
is an environmentally benign solvent.
2.Results and Discussion
Novel phosphine core dendrimers 1Gn[H] (n = 0–3), which are shown in Figure 1, were
synthesized as follows (Scheme 1). An N,N-dimethylformamide (DMF) solution of
tris(4-hydroxyphenyl)phosphine oxide 2 and poly(benzyl ether) dendritic bromide 3Gn[H] was
stirred at 70 ºC in the presence of potassium carbonate and a catalytic amount of 18-crown-6 under
an argon atmosphere. The obtained dendritic phosphine oxide 4Gn[H] was reduced by
trichlorosilane in degassed xylene at 120 ºC to afford the dendritic phosphine 1Gn[H]. All
transformations were carried out in good chemical yields in all generations.
Scheme 1 Preparation of 1Gn[H] (n = 0–3)
3

ACCEPTED MANUSCRIPT
We examined the utility of the dendrimer 1Gn[H] (n = 0–3) as a phosphine ligand by performing
the Suzuki–Miyaura reaction using the corresponding 1Gn[H]–palladium catalyst (Table 1).
The coupling reactions were carried out by using 4-iodotoluene 5a and phenylboronic acid 6a
with 0.5 mol% of various generations of 1Gn[H]–palladium catalysts, which were prepared from
3
1
Gn[H] and [PdCl(
η
-C H )] in situ (P/Pd = 1/1), in 1,4-dioxane at 50 ºC for 4 h. As a result, the
3
5
2
corresponding cross-coupling product 7a was obtained in comparable yields in all generations,
contrary to our expectations. In addition, the second-generation 1G2[H]–palladium catalyst
prepared at a P/Pd ratio of 2/1 afforded a slightly lower chemical yield of 7a than the catalyst
prepared at P/Pd = 1/1, as shown in Table 1, column G2.
a
Table 1 Suzuki–Miyaura reaction in 1,4-dioxane catalyzed by the 1Gn[H]–palladium complex
G0
78
G1
76
G2
G3
77
b
c
Yield (%)
84 (75)
a
3
Reaction Conditions: 1Gn[H] (0.0055 equiv.), [PdCl(
η -C H )] (0.0025 equiv., 0.5 mol% Pd), 5a
3 5 2
(
1 equiv.), 6a (1.5 equiv.), Cs CO (4.5 equiv.), 1,4-dioxane (0.5 M based on 5a), carried out at 50
2
3
ºC for 4 h.
b
Isolated yield.
c
P/Pd = 2/1.
Next, we synthesized the dendritic phosphine having carboxylic groups at the peripheral layer
1
Gn[CO H], which was suitable for an aqueous media Suzuki–Miyaura reaction (Scheme 2).
2
Phosphine core dendrimers 1Gn[CO Me] were synthesized according to a procedure similar to that
2
used for 1Gn[H]. Phosphine core dendrimers having carboxylic groups 1Gn[CO H] were obtained
2
by hydrolysis of 1Gn[CO Me] with potassium hydroxide in degassed aqueous solution
2
4

ACCEPTED MANUSCRIPT
(
THF−methanol−H O) at 50 ºC, followed by protonation of the product with hydrochloric acid. All
2
1
2
transformations were carried out in good chemical yields in all generations.
Scheme 2 Preparation of 1Gn[CO H] (n = 0–3)
2
Then, we examined the utility of the dendrimer 1Gn[CO H] as a phosphine ligand by performing
2
the Suzuki–Miyaura reaction using the corresponding amphiphilic 1Gn[CO K]–palladium catalyst
2
(n = 0–3) in water (Table 2).
The coupling reactions were carried out by using iodoaryl 5 and phenylboronic acid 6a with 0.5
mol% of various generations of 1Gn[CO K]–palladium catalysts (n = 0–3) in water at 50 ºC for 4 h.
2
Although the 1Gn[CO K]–palladium catalysts had micelle-like structures, the reaction mixture was
2
13
a dispersion mixture. In all cases of 3-iodotoluene, 4-iodotoluene, and 4’-iodoacetophenone, the
chemical yield of the coupling product 7 was enhanced by the increase in the generation number of
1
4
the 1Gn[CO K]–palladium catalyst. This was especially true when using 4-iodotoluene: the
2
third-generation 1G3[CO K]–palladium catalyst afforded a 90% chemical yield in this case (Table 2,
2
15
entry 2), which was higher than the yield when a commercially available TPPTS –palladium
catalyst was used (76% yield). The relationship between the generation number of the dendritic
5
,6,16
catalyst and the chemical yields is one of the positive dendritic effects.
On the other hand, by
employing the hydrophobic third-generation 1G3[H]–palladium catalyst in water, the coupling
5

ACCEPTED MANUSCRIPT
reaction between 4-iodotoluene and 6a afforded a poor chemical yield, probably due to the low
1
7
solubility of the 1G3[H]–palladium complex in water (16%; Table 2, entry 2, column G3). As a
result, we consider that not only the poly(benzyl ether) dendron as a hydrophobic reaction field but
also a dispersion formation in a reaction mixture is necessary to catalyze an aqueous media
Suzuki–Miyaura reaction.
a
Table 2 Suzuki–Miyaura reaction in water catalyzed by the 1Gn[CO K]–palladium complex
2
b
Entry
R in 5
Yield (%)
G0
30
37
14
G1
G2
57
81
50
G3
82
1
2
3
3-CH3
4-CH3
42
73
34
c
90 (16)
4-CH CO
74
3
a
3
Reaction Conditions: 1Gn[CO K] (0.0055 equiv.), [PdCl(
η
-C H )] (0.0025 equiv., 0.5 mol% Pd),
2
3
5 2
5
(1 equiv.), 6a (1.5 equiv.), K CO (4.5 equiv.), H O (0.5 M based on 5), carried out at 50 ºC for 4
2 3 2
h.
b
Isolated yield.
c
1
G3[H] was used instead of 1G3[CO K].
2
In the case of this series of amphiphilic dendritic phosphine ligands 1Gn[CO K], a non-dendritic
2
1
G0[CO K] has 3, the first-generation 1G1[CO K] has 6, the second-generation 1G2[CO K] has 12,
2
2
2
and the third-generation 1G3[CO K] has 24 CO K moieties. To confirm the effect of the number of
2
2
CO K groups as surfactants to form dispersions, we carried out the Suzuki–Miyaura reaction of
2
4
-iodotoluene 5a and phenylboronic acid 6a by employing a non-dendritic 1G0[CO K]–palladium
2
catalyst having 3 CO K moieties and potassium benzoate 8[CO K] or 9[CO K] (x
2
2
2
equiv./1G0[CO K]) with the same number of CO K moieties of the dendritic ligand 1Gn[CO K] (n
2
2
2
6

ACCEPTED MANUSCRIPT
=
1–3) (Table 3). The structure of 8[CO K] is similar to that of the peripheral layer of the dendritic
2
phosphine ligand 1Gn[CO K]. 9[CO K] has a surfactant-like structure, including a large
2
2
hydrophobic unit and a CO K group.
2
As a result, the yields of the coupling product 7a were rather low in all cases, and the chemical
yields of 7a derived using a surfactant-like 9[CO K] were lower than those derived using potassium
2
benzoate 8[CO K] in each generation. Thus the addition of 8[CO K] or 9[CO K] was not effective
2
2
2
for increasing the chemical yield of 7a. Based on these results, it can be concluded that the
introduction of hydrophilic groups to the peripheral layer of poly(benzyl ether) dendrons as a
5
a,b
hydrophobic reaction field is essential to an efficient aqueous media Suzuki–Miyaura reaction.
Table 3 Suzuki−Miyaura reaction in water catalyzed by the 1G0[CO K]–palladium complex and
2
a
8
[CO K] or 9[CO K] with the same number of CO K moieties of 1Gn[CO K] (n = 1–3)
2 2 2 2
b
Entry 8[CO K] or 9[CO K] x equiv./1G0[CO K]
Yield (%)
2
2
2
1
2
3
4
5
6
8[CO K]
3
9
32
25
18
22
21
16
2
8[CO K]
2
8[CO K]
21
3
2
9[CO K]
2
9[CO K]
9
2
9[CO K]
21
2
a
Reaction Conditions: 8[CO K] or 9[CO K] (0.0055x equiv.), 1G0[CO K] (0.0055 equiv.),
2
2
2
3
[
PdCl(η -C H )] (0.0025 equiv., 0.5 mol% Pd), 5a (1 equiv.), 6a (1.5 equiv.), K CO (4.5 equiv.),
3 5 2 2 3
7

ACCEPTED MANUSCRIPT
H O (0.5 M based on 5a), carried out at 50 ºC for 4 h.
2
b
Isolated yield.
Next, by employing the third-generation 1G3[CO K]–palladium catalyst, which afforded the
2
highest chemical yield in Table 2, we examined the amount of palladium catalyst required for an
aqueous media Suzuki–Miyaura reaction, as shown in Table 4. The results showed that a catalytic
amount of 0.2 mol% was insufficient to promote an aqueous media Suzuki–Miyaura reaction. 0.5
mol% of 1G3[CO K]–palladium catalyst afforded the coupling product 7a in the highest chemical
2
yield (90%).
a
Table 4 Suzuki–Miyaura reaction in water catalyzed by the 1G3[CO K]–palladium complex
2
Pd catalyst (x mol%)
0.2
30
0.5
90
1
b
Yield (%)
83
a
The reaction conditions were the same as those indicated in Table 2.
Isolated yield.
b
Finally, by employing 0.5 mol% of the third-generation 1G3[CO K]–palladium catalyst, we
2
performed various Suzuki–Miyaura reactions in water until 5 was consumed (Table 5). When
iodoarenes were used, by introducing an acetyl group as an electron-withdrawing group to 5, the
reactivity was enhanced and the coupling reaction was completed within 2 h (Table 5, entry 4). In
contrast, although the reactivity decreased by the introduction of a methoxy group, the reaction
proceeded to afford 7e for 20 h in a 98% chemical yield (Table 5, entry 5). This tendency in the
reactivity of 5 is similar to that previously reported, which is caused by the oxidative addition step
9
d,18
of the palladium catalyst to 5 as the rate-determining step.
On the other hand, by the
introduction of a hydroxyl group to substrate 5, the corresponding coupling product 7f was not
8

ACCEPTED MANUSCRIPT
obtained (Table 5, entry 6). In the case that 4-bromotoluene was used instead of iodoarenes, even
when the coupling reaction was carried out using 1 mol% of the dendritic palladium catalyst for 24
h, the chemical yield of the coupling product 7c was slightly low (63% yield; Table 5, entry 9). On
the other hand, by carrying out the coupling reaction at 100 ºC, 5c was consumed within 1 h to
provide 7c in a 96% yield (Table 5, entry 11). However, when 4-chlorotoluene was used, the
coupling product 7c was not obtained even at 100 ºC (Table 5, entry 12).
a
Table 5 Suzuki−Miyaura reaction using the 1G3[CO K]–palladium catalyst in water
2
1
2
b
Entry
R
X
I
R
Temp. (ºC) Time (h) Product Yield (%)
1
2
3
4
5
6
7
8
2-CH3
3-CH3
4-CH3
H
H
H
H
H
H
50
50
24
10
20
2
7a
7b
7c
7d
7e
7f
92
88
93
90
98
0
I
I
50
4-CH CO
I
50
3
4-CH O
I
50
20
12
5
3
4-OH
H
I
50
I
CH CO
50
7d
7e
7c
7c
7c
7c
85
99
63
82
96
0
3
H
I
CH O
50
20
24
4
3
c
9
4-CH3
4-CH3
4-CH3
4-CH3
Br
Br
Br
Cl
H
H
H
H
50
1
0
1
80
1
100
100
1
1
2
24
a
b
c
The reaction conditions were the same as those indicated in Table 2.
Isolated yield.
1
mol% of Pd catalyst was used.
9

ACCEPTED MANUSCRIPT
3.Conclusion
We prepared several of a new type of a dendritic ligand with a phosphine core. In particular,
when an amphiphilic dendritic phosphine–palladium catalyst was used, the aqueous media
Suzuki–Miyaura reaction proceeded smoothly to provide the corresponding cross-coupling product.
Furthermore, a positive dendritic effect on chemical yields was observed. By employing this new
type of an amphiphilic dendritic catalyst, the range of efficient aqueous media organic syntheses
could be expanded.
4
.Experimental
.1 General
4
1
IR spectra were recorded on a Thermo Electron Nicolet Nexus 470 FT-IR spectrophotometer. H
13
31
NMR (500 MHz), C NMR (125 MHz) and P NMR (202 MHz) spectra were measured with a
1
13
31
JEOL LA-500 spectrometer. Chemical shifts of H, C and P NMR were reported as ppm
1
13
downfield from TMS as an internal standard ( H and C NMR) and from phosphoric acid as an
3
1
external standard ( P NMR) in δ units. Coupling constants (J) were given in hertz (Hz). Mass
spectra were measured with a JEOL MS 600H (FAB; matrix: 3-nitrobenzyl alcohol) and a
Shimadzu AXIMA-CFR (MALDI−TOF; matrix: 2,5-dihydroxybenzoic acid) mass spectrometer.
Microanalyses were performed with a CE Instruments EA1110 elemental analyzer.
Kieselgel 60 F254 (Merck) was used for TLC, and Wakogel C-300 (Wako) was used for silica gel
column chromatography. Dendritic bromides 3Gn[H] (n = 1, 2), methyl 4-(bromomethyl)benzoate
3
G0[CO Me], other reagents, and dry solvents were commercially available and were used as
2
19
20
received. The third-generation dendritic bromide 3G3[H] and 3Gn[CO Me] (n = 1–3) were
2
2
1
prepared by the methods described in the literature. Tris(4-hydroxyphenyl)phosphine oxide 2 and
2
2
4
-(phenoxymethyl)benzoic acid 9[CO H] were also prepared as described previously.
2
4
.2 Synthesis of Dendritic Phosphine Oxide 4Gn[X] from 2 and 3Gn[X] (X = H, CO Me;
2
Scheme 1 and 2): Typical Procedure
A dry DMF solution (44 mL) of tris(4-hydroxyphenyl)phosphine oxide 2 (216 mg, 0.662 mmol),
the third-generation dendritic bromide 3G3[CO Me] (4.50 g, 2.12 mmol), anhydrous potassium
2
carbonate (345 mg, 2.50 mmol), and 18-crown-6 (56.1 mg, 0.212 mmol) was stirred at 70 ºC for 6 h
®
under an argon atmosphere. The reaction mixture was filtered with Celite to remove inorganic salts,
1
0

ACCEPTED MANUSCRIPT
and the filtrate was evaporated to dryness. The residue was purified with silica gel column
chromatography (dichloromethane/acetone = 10/1 as eluent) to obtain 4G3[CO Me] (3.76 g, 0.583
2
mmol) in an 88% yield.
4.2.1. Tris(4-benzyloxyphenyl)phosphine Oxide (4G0[H]). White powder; IR (KBr) 3062, 3029,
−1 1
1
595, 1501, 1288, 1250, 1175, 1121, 987, 696, 545 cm ; H NMR (CDCl ) δ 7.56 (dd, J = 11.5, 8.8
3
Hz, 6H, ArH), 7.44−7.30 (m, 15H, ArH), 7.01 (dd, J = 8.8, 2.0 Hz, 6H, ArH), 5.08 (s, 6H,
13
4
2
OCH Ar); C NMR (CDCl ) δ 161.6 ( J
= 3 Hz), 136.3, 134.0 ( J
= 12 Hz), 128.7, 128.3,
2
3
C−P
C−P
1
3
31
1
27.6, 124.9 ( J = 111 Hz), 114.9 ( J = 13 Hz), 70.1; P NMR (CDCl ) δ = 29.2; FABMS for
C−P
C−P
3
+
C H O PH m/z: Calcd: 597 [(M+H) ]. Found: 597; Anal. Calcd for C H O P: C, 78.51; H,
39
33
4
39 33
4
5
4
3
.58%. Found: C, 78.56; H, 5.48%.
.2.2. Tris{4-(3,5-dibenzyloxybenzyloxy)phenyl}phosphine Oxide (4G1[H]). Foam; IR (KBr) 3455,
−1 1
062, 3030, 2931, 1595, 1499, 1453, 1292, 1248, 1157, 1118, 696 cm ; H NMR (CDCl ) δ 7.55
3
(dd, J = 11.7, 8.7 Hz, 6H, ArH), 7.43−7.27 (m, 30H, ArH), 6.99 (dd, J = 8.7, 2.1 Hz, 6H, ArH), 6.65
1
3
(
d, J = 2.1 Hz, 6H, ArH), 6.57 (t, J = 2.1 Hz, 3H, ArH), 5.02 (s, 18H, OCH Ar); C NMR (CDCl )
2
3
2
δ 161.3, 160.12, 160.05, 139.1, 138.6, 136.7, 133.9 ( J
= 12 Hz), 128.6, 128.0, 127.5, 124.8
C−P
1
3
31
(
JC−P = 111 Hz), 114.8 ( J = 13 Hz), 106.4, 101.6, 101.5, 70.0, 69.96, 69.88; P NMR (CDCl )
C−P
3
+
δ 29.3; FABMS for C H O P m/z: Calcd: 1232 [M ]. Found: 1232; Anal. Calcd for C H O P:
8
1
69 10
81 69 10
C, 78.88; H, 5.64%. Found: C, 78.60; H, 5.55%.
.2.3. Tris[4-{3,5-bis(3,5-dibenzyloxybenzyloxy)benzyloxy}phenyl]phosphine Oxide (4G2[H]).
4
−1 1
Foam; IR (KBr) 3031, 2872, 1595, 1452, 1375, 1294, 1156, 1118, 1054, 830, 696 cm ; H NMR
(
CDCl ) δ 7.55 (dd, J = 21.2, 8.6 Hz, 6H, ArH), 7.42−7.27 (m, 60H, ArH), 6.99 (dd, J = 8.6, 1.7 Hz,
3
6H, ArH), 6.66 (d, J = 2.2 Hz, 12H, ArH), 6.63 (d, J = 2.2 Hz, 6H, ArH), 6.55 (t, J = 2.2 Hz, 6H,
ArH), 6.54 (t, J = 2.2 Hz, 3H, ArH), 5.00 (s, 24H, OCH Ar), 4.98 (s, 6H, OCH Ar), 4.95 (s, 12H,
2
2
1
3
4
OCH Ar); C NMR (CDCl ) δ 161.3( J = 3 Hz), 160.12, 160.05, 139.1, 138.6, 136.7, 133.9
C−P
2
3
2
1
3
(
JC−P = 12 Hz), 128.6, 128.0, 127.5, 124.8 ( JC−P = 111 Hz), 114.8 ( J
= 13 Hz), 106.4, 106.4,
C−P
3
1
1
01.6, 101.5, 70.05, 69.96, 69.9; P NMR (CDCl ) δ 29.3; MALDI−TOFMS for C H O PH
3 165 141 22
+
m/z: Calcd.: 2507.0 [(M+H) ]. Found: 2506.9; Anal. Calcd for C H O P: C, 79.05; H, 5.67%.
1
65 141 22
Found: C, 79.08; H, 5.70%.
.2.4. Tris(4-[3,5-bis{3,5-bis(3,5-dibenzyloxybenzyloxy)benzyloxy}benzyloxy]phenyl)phosphine
Oxide (4G3[H]). Foam; IR (KBr) 3031, 2871, 1595, 1451, 1374, 1295, 1155, 1051, 830, 735, 696
4
11

ACCEPTED MANUSCRIPT
−1 1
cm ; H NMR (CDCl ) δ 7.53 (dd, J = 11.3, 8.4 Hz, 6H, ArH), 7.40−7.22 (m, 120H, ArH), 6.95 (d,
3
J = 8.4 Hz, 6H, ArH), 6.67−6.59 (m, 42H, ArH), 6.56−6.49 (m, 21H, ArH), 4.95 (s, 48H, OCH Ar),
2
1
3
4
4
.94−4.88 (m, 42H, OCH Ar); C NMR (CDCl ) δ 161.3 ( J = 2 Hz), 160.1, 160.04, 159.99,
C−P
2
3
2
1
1
39.1, 139.0, 138.6, 136.7, 133.8 ( J = 12 Hz), 128.5, 127.9, 127.5, 124.8 ( J = 110 Hz), 114.7
C−P
C−P
3
31
(
JC−P = 13 Hz), 106.4, 106.3, 101.5, 70.0, 69.9; P NMR (CDCl ) δ 29.1; MALDI−TOFMS for
3
+
C H O PH m/z: Calcd.:5054.5 [(M+H) ]. Found: 5054.1; Anal. Calcd for C H O P:
3
33 285 46
333 285 46
C,79.14; H, 5.68%. Found: C,79.34; H, 5.66%.
.2.5. Tris[4-{4-(methoxycarbonyl)benzyloxy}phenyl]phosphine Oxide (4G0[CO Me]). White
4
2
powder; IR (KBr) 3421, 2952, 1728, 1595, 1499, 1434, 1384, 1281, 1177, 1120, 1019, 834, 755,
−1 1
5
40, 482 cm ; H NMR (CDCl ) δ 8.05 (d, J = 8.3 Hz, 6H, ArH), 7.57 (dd, J = 11.5, 7.8 Hz, 6H,
3
ArH), 7.49 (d, J = 8.3 Hz, 6H, ArH), 7.02 (dd, J = 7.8, 2.0 Hz, 6H, ArH), 5.15 (s, 6H, OCH Ar),
2
13
4
2
3
.92 (s, 9H, OCH ); C NMR (CDCl ) δ 166.7, 161.1 ( J = 2 Hz), 141.3, 133.9 ( J = 11 Hz),
3 3 C−P C−P
1
3
31
1
29.90, 129.87, 126.9, 125.0 ( J = 110 Hz), 114.8 ( J = 12 Hz), 69.3, 52.1; P NMR (CDCl )
C−P
C−P
3
+
δ 28.3; FABMS for C H O P m/z: Calcd: 770 [M ]. Found: 770; Anal. Calcd for C H O P: C,
4
5
39 10
45 39 10
70.12; H, 5.10%. Found: C, 70.12; H, 5.14%.
4.2.6. Tris(4-[3,5-bis{4-(methoxycarbonyl)benzyloxy}benzyloxy]phenyl)phosphine
Oxide
(
4G1[CO Me]). White powder; IR (KBr) 3421, 2952, 1728, 1595, 1499, 1434, 1384, 1281, 1177,
2
−1 1
1
120, 1019, 834, 755, 540, 482 cm ; H NMR (CDCl ) δ 8.04 (d, J = 8.8 Hz, 12H, ArH), 7.57 (dd,
3
J = 11.5, 9.0 Hz, 6H, ArH), 7.47 (d, J = 8.8 Hz, 12H, ArH), 7.00 (dd, J = 9.0, 2.0 Hz, 6H, ArH),
.66 (d, J = 2.0 Hz, 6H, ArH), 6.54 (t, J = 2.0 Hz, 3H, ArH), 5.09 (s, 12H, OCH Ar), 5.02 (s, 6H,
6
2
1
3
4
OCH Ar), 3.91 (s, 18H, OCH ); C NMR (CDCl ) δ 166.8, 161.4 ( J = 2 Hz), 159.9, 141.8,
C−P
2
3
3
2
1
3
1
1
1
7
4
38.9, 133.9 ( J
= 10 Hz), 129.9, 129.8, 127.0, 124.9 ( J
= 110 Hz), 114.9 ( J
= 13 Hz),
C−P
C−P
C−P
3
1
06.6, 101.7, 69.8, 69.5, 52.2; P NMR (CDCl ) δ 28.5; FABMS for C H O PH m/z: Calcd:
3
93 81 22
+
581.5 [(M+H) ]. Found: 1581.8; Anal. Calcd for C H O P: C, 70.63; H, 5.16%. Found: C,
9
3
81 22
0.28; H, 5.01%.
.2.7. Tris{4-(3,5-bis[3,5-bis{4-(methoxycarbonyl)benzyloxy}benzyloxy]benzyloxy)phenyl}
phosphine Oxide (4G2[CO Me]). White powder; IR (KBr) 3421, 2950, 1719, 1596, 1500, 1437,
2
−
1 1
1
2
2
375, 1280, 1157, 1109, 1061, 1019, 832, 755, 475 cm ; H NMR (CDCl ) δ 8.01 (d, J = 8.2 Hz,
3
4H, ArH), 7.55 (dd, J = 11.6, 8.8 Hz, 6H, ArH), 7.45 (d, J = 8.2 Hz, 24H, ArH), 6.99 (dd, J = 8.8,
.1 Hz, 6H, ArH), 6.65 (d, J = 2.1 Hz, 12H, ArH), 6.62 (d, J = 2.1 Hz, 6H, ArH), 6.52 (t, J = 2.1 Hz,
1
2

ACCEPTED MANUSCRIPT
6
1
1
1
H, ArH), 6.50 (t, J = 2.1 Hz, 3H, ArH), 5.06 (s, 24H, OCH Ar), 4.99 (s, 6H, OCH Ar), 4.94 (s,
2
2
1
3
2H, OCH Ar), 3.89 (s, 36H, OCH ); C NMR (CDCl ) δ 166.7, 161.4, 160.0, 159.9, 141.9, 139.4,
2
3
3
2
1
3
38.7, 133.9 ( J
= 11 Hz), 129.9, 129.7, 127.0, 124.8 ( J
= 110 Hz), 114.9 ( J
= 13 Hz),
C−P
C−P
C−P
3
1
06.5, 106.4, 101.6, 69.88, 69.85, 69.4, 52.1; P NMR (CDCl ) δ 28.4; MALDI−TOFMS for
3
+
C H O PH m/z: Calcd.: 3204.0 [(M+H) ]. Found: 3204.1; Anal. Calcd for C H O P: C,
1
89 165 46
189 165 46
70.87; H, 5.19%. Found: C, 70.73; H, 5.01%.
4.2.8. Tris[4-{3,5-bis(3,5-bis[3,5-bis{4-(methoxycarbonyl)benzyloxy}benzyloxy]benzyloxy)
benzyloxy}phenyl]phosphine Oxide (4G3[CO Me]). White powder; IR (KBr) 3421, 2949, 1720,
2
−1 1
1
596, 1448, 1436, 1375, 1280, 1157, 1108, 1057, 1019, 835, 755, 473 cm ; H NMR (CDCl ) δ
3
7.98 (d, J = 8.3 Hz, 48H, ArH), 7.53 (t, J = 8.9 Hz, 6H, ArH), 7.40 (d, J = 8.3 Hz, 48H, ArH), 6.95
(d, J = 8.9 Hz, 6H, ArH), 6.67−6.56 (m, 42H, ArH), 6.55−6.44 (m, 21H, ArH), 5.01 (s, 48H,
13
OCH Ar), 4.94 (s, 6H, OCH Ar), 4.90 (s, 36H, OCH Ar), 3.86 (s, 72H, OCH ); C NMR (CDCl )
2
2
2
3
3
2
δ 166.7, 161.4, 160.1, 160.0, 159.9, 141.9, 139.4, 139.2, 133.9 ( J = 11 Hz), 129.8, 129.7, 126.9,
C−P
3
31
1
14.8 ( J
= 13 Hz), 106.5, 101.6, 101.5, 70.0, 69.8, 69.4, 52.1; P NMR (CDCl ) δ 28.2;
C−P
3
+
MALDI−TOFMS for C H O PH m/z: Calcd.: 6447.3 [(M+H) ]. Found 6447.0; Anal. Calcd for
3
81 333 94
C H O P: C, 70.98; H, 5.21. Found: C, 70.73; H, 5.13%.
381 333 94
4
.3. Synthesis of Dendritic Phosphine 1Gn[X] from 4Gn[X] (X = H, CO Me; Scheme 1 and 2):
2
Typical Procedure
To a solution of the third-generation dendritic phosphine oxide 4G3[CO Me] (796 mg, 0.123
2
mmol) in degassed xylene (12 mL) was added triethylamine (35.0 mg, 0.346 mmol) and
trichlorosilane (43.5 mg, 0.321 mmol) at room temperature with stirring. The mixture was stirred at
120 ºC for 20 h under an argon atmosphere. To a reaction mixture was added dichloromethane (20
mL), water (1 mL), and sodium hydrogen carbonate (ca. 0.2 g), and the thus obtained mixture was
stirred at room temperature for 2 h. After the removal of water by the addition of magnesium sulfate,
®
the mixture was filtered with Celite to remove inorganic salts, and the filtrate was evaporated to
dryness. The residue was purified with silica gel column chromatography (dichloromethane/ethyl
acetate = 3/1 as eluent) to obtain 1G3[CO Me] (751 mg, 1.17 mmol) in a 95% yield.
2
4.3.1. Tris(4-benzyloxyphenyl)phosphine (1G0[H]). White powder; IR (KBr) 3029, 3927, 2868,
−1 1
1
592, 1496, 1243, 1177, 1094, 1001, 830, 739, 696 cm ; H NMR (CDCl ) δ 7.44−7.18 (m, 21H,
3
1
3
ArH), 6.93 (d, J = 8.8 Hz, 6H, ArH), 5.04 (s, 6H, OCH Ar); C NMR (CDCl ) δ 159.4, 136.8,
2
3
1
3

ACCEPTED MANUSCRIPT
C−P
2
1
3
31
1
35.0 ( J
= 21 Hz), 129.3 ( J
= 8 Hz), 128.7, 128.1, 127.6, 115.1 ( J
= 7 Hz), 70.0; P
C−P
C−P
+
NMR (CDCl ) δ −9.4; FABMS for C H O P m/z: Calcd: 580 [M ]. Found: 580; Anal. Calcd for
3
39 33
3
C H O P: C, 80.67; H, 5.73%. Found: C, 80.62; H, 5.53%.
39
33
3
4
2
3
6
1
.3.2. Tris{4-(3,5-dibenzyloxybenzyloxy)phenyl}phosphine (1G1[H]). Glassy; IR (CH Cl ) 3031,
2 2
−1 1
872, 1593, 1496, 1453, 1376, 1241, 1159, 1027, 827, 696 cm ; H NMR (CDCl ) δ 7.47−7.32 (m,
3
0H, ArH), 7.29−7.24 (m, 6H, ArH), 6.96 (d, J = 8.4 Hz, 6H, ArH), 6.71 (d, J = 2.4 Hz, 6H, ArH),
1
3
.62 (d, J = 2.2 Hz, 3H, ArH), 5.06 (s, 12H, OCH Ar), 5.01 (s, 6H, OCH Ar); C NMR (CDCl ) δ
2
2
3
2
1
60.2, 159.2, 139.3, 136.7, 135.0 ( J
= 20.9 Hz), 129.2 ( J
= 7.5 Hz), 128.6, 128.1, 127.5,
C−P
C−P
3
31
1
15.1 ( J = 7.6 Hz), 106.4, 101.6, 70.1, 69.9; P NMR (CDCl ) δ −9.4; FABMS for C H O P
C−P
3
81 69
9
+
m/z: Calcd: 1216 [M ]. Found: 1216; Anal. Calcd for C H O P: C, 79.91; H, 5.71%. Found: C,
8
1
69
9
80.24; H, 5.82%.
4.3.3. Tris[4-{3,5-bis(3,5-dibenzyloxybenzyloxy)benzyloxy}phenyl]phosphine (1G2[H]). Glassy; IR
−
1 1
(
CH Cl ) 3032, 2873, 1594, 1496, 1453, 1376, 1241, 1159, 1027, 828, 696 cm ; H NMR (CDCl )
2
2
3
δ 7.41−7.18 (m, 66H, ArH), 6.91 (d, J = 8.4 Hz, 6H, ArH), 6.66 (d, J = 1.6 Hz, 12H, ArH), 6.64 (d,
J = 2.0 Hz, 6H, ArH), 6.55 (t, J = 2.0 Hz, 6H, ArH), 6.53 (t, J = 2.0 Hz, 3H, ArH), 5.00 (s, 24H,
1
3
OCH Ar), 4.94 (s, 18H, OCH Ar); C NMR (CDCl ) δ 160.3, 160.2, 159.4, 139.31, 139.28, 136.9,
2
2
3
2
3
1
6
35.1 ( J = 20.5 Hz), 129.3, 128.7, 128.1, 127.7, 115.1 ( JC−P = 7.6 Hz), 106.5, 101.7, 70.2, 70.1,
C−P
3
1
9.9, P NMR (CDCl ) δ −9.2; MALDI−TOFMS for C H O PH m/z: Calcd.: 2490.99
3
165 141 21
+
[
(M+H) ]. Found: 2490.83; Anal. Calcd for C H O P: C, 79.56; H, 5.71%. Found: C, 79.59; H,
165 141 21
5
4
.83%.
.3.4.
Tris(4-[3,5-bis{3,5-bis(3,5-dibenzyloxybenzyloxy)benzyloxy}benzyloxy]phenyl)phosphine
(1G3[H]). Foam; IR (KBr) 3030, 2871, 1720, 1596, 1452, 1374, 1295, 1156, 1054, 831, 736, 696
−1 1
cm ; H NMR (CDCl ) δ 7.38−7.23 (m, 120H), 7.18 (dd, J = 8.2, 7.5 Hz, 6H), 6.87 (d, J = 8.2 Hz,
3
6H), 6.65−6.61 (m, 42H), 6.53 (t, J = 2.0 Hz, 15H), 6.50 (t, J = 2.0 Hz, 6H), 4.96 (s, 48H), 4.90 (s,
1
3
2
4
2H); C NMR (CDCl ) δ 160.1, 160.03, 160.00, 159.2, 139.16, 139.12, 136.7, 134.9 ( J
= 21
3
C−P
1
3
Hz), 128.5, 129.2 ( J
= 9.1 Hz), 128.0, 127.5, 115.0 ( J
= 7 Hz), 106.4, 106.3, 101.5, 70.0,
C−P
C−P
3
1
6
9.9, 69.8; P NMR (CDCl ) δ −9.34; MALDI−TOFMS for C H O PH m/z: Calcd.:5037.99
3 333 285 45
+
[
(M+H) ]. Found: 5037.89; Anal. Calcd for C H O P: C, 79.39; H, 5.70%. Found: C, 79.28; H,
333 285 45
5
.60%.
.3.5. Tris[4-{4-(methoxycarbonyl)benzyloxy}phenyl]phosphine (1G0[CO Me]). White powder; IR
4
2
1
4

ACCEPTED MANUSCRIPT
−1 1
(
KBr) 3422, 2949, 1720, 1592, 1496, 1435, 1281, 1241, 1176, 1108, 1018, 825, 755 cm ; H NMR
(
CDCl ) δ 8.04 (d, J = 8.3 Hz, 6H, ArH), 7.48 (d, J = 8.3 Hz, 6H, ArH), 7.21 (dd, J = 8.8, 7.3 Hz,
3
1
3
6
H, ArH), 6.92 (dd, J = 8.8, 1.0 Hz, 6H, ArH), 5.11 (s, 6H, OCH Ar), 3.92 (s, 9H, OCH ); C
2
3
2
1
NMR (CDCl ) δ 166.8, 159.0, 141.9, 135.0 ( J
= 21 Hz), 129.9, 129.7, 129.4 ( J = 9 Hz),
C−P
3
C−P
3
31
1
26.9, 115.0 ( J
= 7 Hz), 69.2, 52.1; P NMR (CDCl ) δ −9.37; FABMS for C H O PH m/z:
C−P 3 45 39 9
+
Calcd: 755 [(M+H) ]. Found: 755; Anal. Calcd for C H O P: C, 71.61; H, 5.21%. Found: C,
4
5
39
9
71.96; H, 5.19%.
4
.3.6. Tris(4-[3,5-bis{4-(methoxycarbonyl)benzyloxy}benzyloxy]phenyl)phosphine (1G1[CO Me]).
2
White powder; IR (KBr) 3421, 2949, 1719, 1595, 1496, 1436, 1280, 1159, 1107, 1066, 1107, 1066,
−
1 1
1
6
019, 829, 755 cm ; H NMR (C D ) δ 8.11 (d, J = 8.0 Hz, 12H, ArH), 7.43 (dd, J = 8.5, 7.0 Hz,
6 6
H, ArH), 7.15 (d, J = 8.0 Hz, 12H, ArH), 6.91 (d, J = 8.5 Hz, 6H, ArH), 6.68 (d, J = 2.0 Hz, 6H,
ArH), 6.56 (t, J = 2.0 Hz, 3H, ArH), 4.71 (s, 6H, OCH Ar), 4.59 (s, 12H, OCH Ar), 3.49 (s, 18H,
2
2
13
2
OCH ); C NMR (C D ) δ 166.4, 160.5, 159.8, 142.2, 140.1, 135.7 ( J = 21 Hz), 130.4, 130.1,
3
6
6
C−P
3
31
1
27.3, 115.6 ( J
= 7 Hz), 106.9, 102.1, 70.0, 69.4, 51.6; P NMR (C D ) δ −9.8; FABMS for
C−P 6 6
+
C H O P m/z: Calcd: 1564 [M ]. Found: 1564; Anal. Calcd for C H O P: C, 71.35; H, 5.22%.
93
81 21
93 81 21
Found: C, 71.42; H, 5.14%.
.3.7. Tris{4-(3,5-bis[3,5-bis{4-(methoxycarbonyl)benzyloxy}benzyloxy]benzyloxy)phenyl}
phosphine (1G2[CO Me]). White powder; IR (KBr) 3421, 2950, 1720, 1596, 1496, 1436, 1280,
4
2
−1 1
1
158, 1108, 1060, 1019, 832, 755 cm ; H NMR (THF−d ) δ 7.97 (d, J = 8.2 Hz, 24H, ArH), 7.48
8
(d, J = 8.2 Hz, 24H, ArH), 7.16 (t, J = 8.3 Hz, 6H, ArH), 6.92 (d, J = 8.3 Hz, 6H, ArH), 6.71 (d, J =
1
4
1
1
.8 Hz, 12H, ArH), 6.67 (s, 6H, ArH), 6.57 (s, 6H, ArH), 6.55 (s, 3H, ArH), 5.11 (s, 24H, OCH Ar),
2
1
3
.97 (s, 18H, OCH Ar), 3.82 (s, 36H, OCH ); C NMR (THF−d ) δ 166.8, 161.1, 160.9, 160.4,
2
3
8
2
3
43.5, 140.9, 140.6, 135.7 ( J = 21 Hz), 130.6, 130.3, 127.7, 115.7 ( J = 7 Hz), 107.1, 107.0,
C−P
C−P
31
02.1, 70.5, 70.4, 69.9, 52.1; P NMR (THF−d ) δ −9.6; MALDI−TOFMS for C H O PH m/z:
8
189 165 45
+
Calcd.: 3188.1 [(M+H) ]. Found 3188.0; Anal. Calcd for C H O P: C, 71.22; H, 5.22%. Found:
1
89 165 45
C, 71.34; H, 5.35%.
.3.8. Tris[4-{3,5-bis(3,5-bis[3,5-bis{4-(methoxycarbonyl)benzyloxy}benzyloxy]benzyloxy)
benzyloxy}phenyl]phosphine (1G3[CO Me]). White powder; IR (KBr) 3421, 2949, 1720, 1596,
4
2
−1 1
1
496, 1436, 1280, 1157, 1108, 1056, 1019, 835, 755 cm ; H NMR (CDCl ) δ 7.98 (d, J = 8.2 Hz,
3
48H, ArH), 7.40 (d, J = 8.2 Hz, 48H, ArH), 7.17 (dd, J = 8.3, 7.3 Hz, 6H, ArH), 6.86 (d, J = 8.3 Hz,
1
5

ACCEPTED MANUSCRIPT
6
4
1
1
H, ArH), 6.64−6.58 (m, 42H, ArH), 6.53−6.43 (m, 21H, ArH), 5.00 (s, 48H, OCH Ar), 4.89 (s,
2
1
3
2H, OCH Ar), 3.86 (s, 72H, OCH ); C NMR (CDCl ) δ 166.7, 160.0, 159.8, 159.1, 141.8, 139.4,
2
3
3
2
3
39.23, 139.18, 134.9 ( J = 22 Hz), 129.8, 129.6, 126.9, 115.0 ( J = 10 Hz), 106.40, 106.35,
C−P
C−P
3
1
01.5, 101.4, 69.8, 69.7, 69.3, 52.1; P NMR (CDCl ) δ −9.43; MALDI−TOFMS for C H O P
3
381 333 93
+
m/z: Calcd.: 6430.3 [M ]. Found 6430.2; Anal. Calcd for C H O P: C, 71.16; H, 5.22%. Found:
3
81 333 93
C, 71.55; H, 5.32%.
4
.4. Synthesis of Dendritic Phosphine 1Gn[CO H] from 1Gn[CO Me] (Scheme 2): Typical
2 2
Procedure
The third-generation dendritic phosphine 1G3[CO Me] (671 mg, 0.104 mmol) and potassium
2
hydroxide (464 mg, 8.27 mmol) in a degassed 1:1 (v/v) mixture (8 mL) of THF and methanol was
stirred at 50 ºC under an argon atmosphere. Whenever the precipitation of potassium carboxylate
occurred, a small portion of degassed water (total ca. 2 mL) was poured into the reaction mixture to
dissolve the precipitate. When a precipitation did not form, the hydrolysis was continued by heating
at 50 ºC for 24 h. The reaction mixture was evaporated in vacuo to remove organic solvent, and the
residue was added dropwise to 1 M hydrochloric acid (36 mL) to protonate the product that was
precipitated from solution. The precipitated product was collected by filtration, followed by
washing with water and dichloromethane, and was dried at 55 ºC for 24 h to give 1G3[CO H] (553
2
mg, 0.0907 mmol) in an 87% yield.
4
.4.1. Tris{4-(4-carboxybenzyloxy)phenyl}phosphine (1G0[CO H]). White powder; IR (KBr) 3447,
2
−1 1
3
021, 2664, 2541, 1690, 1592, 1495, 1421, 1283, 1239, 1175, 1094, 1018, 825, 755 cm ; H NMR
(
DMF−d ) δ 13.3 (brs, 3H, ArCO H), 8.09 (d, J = 8.5 Hz, 6H, ArH), 7.67 (d, J = 8.5 Hz, 6H, ArH),
7 2
1
3
7
.29 (dd, J = 8.5, 7.3 Hz, 6H, ArH), 7.16 (d, J = 8.5 Hz, 6H, ArH), 5.30 (s, 6H, OCH Ar); C NMR
2
2
1
(
DMF−d ) δ 166.5, 158.6, 141.6, 134.2 ( J = 22 Hz), 130.0, 129.0, 128.7 ( J = 9 Hz), 126.8,
7 C−P C−P
3
31
1
14.6 ( J = 7 Hz), 68.3; P NMR (DMF−d ) δ −9.85; FABMS for C H O PH m/z: Calcd: 713
C−P 7 42 33 9
+
[
(M+H) ]. Found: 713; Anal. Calcd for C H O P·0.1H O: C, 70.60; H, 4.68%. Found: C, 70.36; H,
42 33 9 2
4
4
.67%.
.4.2. Tris[4-{3,5-bis(4-carboxybenzyloxy)benzyloxy}phenyl]phosphine (1G1[CO H]). White
2
powder; IR (KBr) 3421, 3018, 2873, 2663, 2537, 1690, 1594, 1495, 1452, 1420, 1375, 1288, 1240,
−1 1
1
156, 1066, 1018, 828, 754 cm ; H NMR (DMF−d ) δ 11.5 (brs, 3H), 8.09 (d, J = 8.5 Hz, 12H,
7
ArH), 7.67 (d, J = 8.5 Hz, 12H, ArH), 7.29 (dd, J = 8.5, 7.3 Hz, 6H, ArH), 7.13 (d, J = 8.5 Hz, 6H,
1
6

ACCEPTED MANUSCRIPT
1
3
ArH), 6.88 (brs, 6H, ArH), 6.80 (brs, 3H, ArH), 5.30 (s, 12H, OCH Ar), 5.15 (s, 6H, OCH Ar); C
2
2
2
NMR (DMF−d ) δ 167.8, 160.6, 160.1, 143.0, 140.5, 135.4 ( J
= 22 Hz), 131.3, 130.3, 129.9
7
C−P
1
3
31
(
JC−P = 8 Hz), 128.1, 115.8 ( JC−P = 7 Hz), 107.5, 101.9, 70.1, 69.8; P NMR (DMF−d ) δ −9.94;
7
+
FABMS for C H O P m/z: Calcd: 1480 [M ]. Found: 1480; Anal. Calcd. for C H O P·H O: C,
8
7
69 21
87 69 21
2
69.69; H, 4.77%. Found: C, 69.92; H, 4.65%.
4.4.3. Tris(4-[3,5-bis{3,5-bis(4-carboxybenzyloxy)benzyloxy}benzyloxy]phenyl)
phosphine
(
1G2[CO H]). Light yellow powder; IR (KBr) 3421, 2925, 2663, 2542, 1691, 1594, 1497, 1449,
2
−
1 1
1
8
7
3
419, 1374, 1281, 1239, 1155, 1059, 1018, 830, 754 cm ; H NMR (DMF−d ) δ 13.1 (brs, 12H),
7
.06 (d, J = 8.5 Hz, 24H, ArH), 7.65 (d, J = 8.5 Hz, 24H, ArH), 7.27 (dd, J = 8.5, 7.3 Hz, 6H, ArH),
.12 (d, J = 8.5 Hz, 6H, ArH), 6.88 (s, 12H, ArH), 6.85 (s, 6H, ArH), 6.78 (brs, 6H, ArH), 6.74 (brs,
13
H, ArH), 5.28 (s, 24H, OCH Ar), 5.20 (s, 6H, OCH Ar), 5.15 (s, 12H, OCH Ar); C NMR
2
2
2
2
(
DMF−d ) δ 167.8, 160.7, 160.6, 160.1, 143.0, 140.6, 140.4, 135.4 ( J
= 21 Hz), 131.3, 130.3,
7
C−P
1
3
31
1
29.9 ( J
= 11 Hz), 128.1, 115.9 ( J
= 7 Hz), 107.5, 107.4, 101.9, 70.2, 69.8; P NMR
C−P
C−P
+
(
DMF−d ) δ −9.87; MALDI−TOFMS for C H O PH m/z: Calcd.: 3019.86 [(M+H) ]. Found:
7
177 141 45
3019.81; Anal. Calcd for C H O P·2H O: C, 69.59; H, 4.78%. Found: C, 69.57; H, 4.73%.
177 141 45 2
4.4.4. Tris{4-(3,5-bis[3,5-bis{3,5-bis(4-carboxybenzyloxy)benzyloxy}benzyloxy]benzyloxy)phenyl}
phosphine (1G3[CO H]). Light yellow powder; IR (KBr) 3422, 3068, 2924, 1692, 1595, 1317,
2
−
1 1
1
7
6
153, 1288 cm ; H NMR (DMF−d ) δ13.3 (brs, 24H, ArCO H), 8.06 (d, J = 8.2 Hz, 48H, ArH),
7 2
.62 (d, J = 8.2 Hz, 48H, ArH), 7.25 (dd, J = 8.2, 7.3 Hz, 6H, ArH), 7.09 (d, J = 8.2 Hz, 6H, ArH),
.89−6.81 (m, 42H, ArH), 6.78−6.70 (m, 21H, ArH), 5.24 (s, 48H, OCH Ar), 5.18−5.06 (m, 42H,
2
1
3
OCH Ar); C NMR (DMF−d ) δ 166.5, 159.44, 159.39, 159.3, 141.7, 139.3, 139.2, 139.0, 134.2
2
7
2
3
(
JC−P = 21 Hz), 129.9, 129.0, 126.8, 114.6 ( J = 3 Hz), 106.2, 106.1, 100.6, 100.5, 68.96, 68.95,
C−P
3
1
6
8.86, 68.5; P NMR (DMF−d ) δ −9.74; MALDI−TOFMS for C H O PH m/z: Calcd.:
7 357 285 93
+
6
094.64 [(M+H) ]. Found: 6094.67; Anal. Calcd for C H O P·3H O: C, 69.74; H, 4.77%.
357 285 93 2
Found: C, 69.80; H, 4.74%.
4.5. Suzuki–Miyaura Reaction (Table 1–5): General Procedure
1
Gn[CO K] was prepared by mixing 1Gn[CO H] (0.0184 mmol) and potassium hydroxide (1.1
2
2
equiv./CO H) at room temperature in water (1.5 mL) under an argon atmosphere. By the addition of
2
3
[
PdCl(
η
-C H )] (0.0084 mmol) to 1Gn[CO K] aqueous solution, the 1Gn[CO K]–palladium
3
5
2
2
2
catalyst was prepared with stirring for 15 min. To a mixture of 5 (3.34 mmol), 6 (5.01 mmol), and
1
7

ACCEPTED MANUSCRIPT
potassium carbonate (15.0 mmol) in water (5.2 mL) was added the above-prepared
1
Gn[CO K]–palladium aqueous solution at 0 ºC. The resulting mixture was stirred for 4 h at 50 ºC.
2
The reaction mixture was extracted with diethyl ether four times, and the combined organic layers
were washed with brine then dried over anhydrous magnesium sulfate. The solution was
concentrated under reduced pressure, and the residue was purified with silica gel column
chromatography to obtain the coupling product 7.
3
For the experiment described in Table 1, 1Gn[H] and [PdCl(
η
-C H )] were stirred in
3
5 2
1,4-dioxane, and the subsequent Suzuki–Miyaura reaction was also carried out in 1,4-dioxane by
use of cesium carbonate stead of potassium carbonate.
For the experiment described in Table 3, potassium hydroxide (1.1 equiv./total CO H) was added
2
to a mixture of a non-dendritic 1G0[CO H] and 8[CO H] or 9[CO H] in water. After the reaction
2
2
2
3
mixture was completely dissolved, [PdCl(η -C H )] was added to the aqueous mixture.
3 5 2
Cross-coupling products 7a–7e are known compounds, and their NMR spectra are in accordance
2
3
with those reported in the literature.
Acknowledgement
This work was supported by Industrial Technology Research Grant Program in ’04 from New
Energy and Industrial Technology Development Organization (NEDO) of Japan.
References and Notes
1
. (a) He, Y.-M.; Feng, Y.; Fan, Q.-H. Acc. Chem. Res. 2014, 47, 2894–2906; (b) Caminade,
A.-M.; Ouali, A.; Keller, M.; Majoral, J.-P. Chem. Soc. Rev. 2012, 41, 4113–4125; (c) Astruc,
D.; Boisselier, E.; Ornelas, C. Chem. Rev. 2010, 110, 1857–1959; (d) Hourani, R.; Kakkar, A.
Macromol. Rapid Commun. 2010, 31, 947–974; (e) de Jesus, E.; Flores, J. C. Ind. Eng. Chem.
Res. 2008, 47, 7968–7981.
2
. (a) Wang, D.; Astruc, D. Coord. Chem. Rev. 2013, 257, 2317–2334; (b) Tsuji, Y; Fujihara, T.
Bull. Korean. Chem. Soc. 2007, 28, 1902–1909.
3
. (a) Helms, B.; Fréchet, J. M. J. Adv. Synth. Catal. 2006, 348, 1125–1148; (b) Reek, J. N. H.;
Arevalo, S.; van Heerbeek, R.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Adv. Catal. 2006, 49,
1
8

ACCEPTED MANUSCRIPT
1–151; (c) Grayson, S. M.; Fréchet, J. M. J. Chem. Rev. 2001, 101, 3819–3867; (d) Astruc, D.;
7
Chardac, F. Chem. Rev. 2001, 101, 2991–3023.
4. (a) Fujita, K.; Sato, J.; Inoue, K.; Tsuchimoto, T.; Yasuda, H. Tetrahedron Lett. 2014, 55,
3
013–3016; (b) Fujita, K.; Kujime, M.; Muraki, T. Bull. Chem. Soc. Jpn. 2009, 11, 2305–2307;
(c) Fujihara, T.; Yoshida, S.; Terao, J.; Tsuji, Y. Org. Lett. 2009, 11, 2121–2124; (d) Fujihara,
T.; Yoshida, S.; Ohta, H.; Tsuji, Y. Angew. Chem. Int. Ed. 2008, 47, 8310–8314.
. (a) Muraki, T.; Fujita K.; Kujime, M. J. Org. Chem. 2007, 72, 7863–7870; (b) Muraki, T.; Fujita
K.; Terakado, D. Synlett 2006, 2646–2648; (c) Fujita, K.; Muraki, T.; Hattori, H.; Sakakura, T.
Tetrahedron Lett. 2006, 47, 4831–4834.
5
6
. (a) Caminade, A.-M.; Ouali, A.; Laurent, R.; Turrin, C.-O.; Majoral, J.-P. Chem. Soc. Rev. 2015,
4
4, 3890–3899; (b) Servin, P.; Laurent, R.; Gonsalvi, L.; Tristany, M.; Peruzzini, M.; Majoral,
J.-P.; Caminade, A.-M. Dalton Trans., 2009, 4432–4434; (c) Snelders, D. J. M.; van Koten, G.;
Gebbink, R. J. M. K. J. Am. Chem. Soc. 2009, 131, 11407–11416; (d) Wang, Z.-J.; Deng, G.-J.;
Li, Y.; He, Y.-M.; Tang, W.-J.; Fan, Q.-H. Org. Lett. 2007, 9, 1243–1246; (e) Helms, B.; Liang,
C. O.; Hawker, C. J.; Fréchet, J. M. J. Macromolecules 2005, 38, 5411–5415; (f) Fujihara, T.;
Obora, Y.; Tokunaga, M.; Sato, H.; Tsuji, Y. Chem. Commun. 2005, 4526–4528.
7
. Previously reported phosphine core dendrimers: (a) Ma, B.; Miao, T.; Sun, Y.; He, Y.; Liu, J.;
Feng, Y.; Chen, H.; Fan, Q.-H. Chem. Eur. J. 2014, 20, 9969–9978 (b) Caminade, A.-M.;
Laurent, P. S. R.; Majoral, J.-P. Chem. Soc. Rev. 2008, 37, 56–67; (c) Wu, L.; Li, B.-L.; Huang,
Y.-Y.; Zhou, H.-F.; He, Y.-M.; Fan, Q.-H. Org. Lett. 2006, 8, 3605–3608; (d) Oosterom, G. E.;
Steffens, S.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Top. Cat. 2002, 19,
6
1–73; (e) Balaji, B. S.; Obora, Y.; Ohara, D.; Koide, S.; Tsuji, Y. Organometallics 2001, 20,
5
342–5350.
8
. Our preliminary report: Hattori, H.; Fujita, K.; Muraki, T.; Sakaba, A. Tetrahedron Lett. 2007,
8, 6817–6820.
4
9
. (a) Lennox, A. J. J.; Lloyd-Jones, G. C. Chem. Soc. Rev. 2014, 43, 412–443; (b) Lennox, A. J. J.;
Lloyd-Jones, G. C. Angew. Chem. Int. Ed. 2013, 52, 7362–7370; (c) Miyaura, N. Top. Curr.
Chem. 2002, 219, 11−59; (d) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
0. (a) Pinto, J.; Silva, V. L. M.; Silva, A. M. G.; Santos, L. M. N. B. F.; Silva, A. M. S. J. Org.
Chem. 2015, 80, 6649–6659; (b) Handa, S.; Slack, E. D.; Lipshutz, B. H. Angew. Chem. Int. Ed.
1
1
9

ACCEPTED MANUSCRIPT
015, 54, 11994–11998; (c) Liu, Y.-S.; Gu, N.-N.; Liu, P.; Ma, X.-W.; Liu, Y.; Xie, J.-W.; Dai,
2
B. Tetrahedron 2015, 71, 7985–7989.
1
1
1. (a) Shaughnessy, K. H. Chem. Rev. 2009, 109, 643–710; (b) Li, C.-J.; Chen, L. Chem. Soc. Rew.
2
006, 35, 68–82; (c) Li, C.-J. Chem. Rev. 2005, 105, 3095–3165; (d) Cornils, B.; Herrmann, W.
A. Eds. Aqueous-Phase Organometallic Catalysis; Wiley-VCH: Weinheim, 2004.
2. We confirmed the formation of the 1G3[CO H]–palladium complex by mixing 1G3[CO H] and
2
2
3
31
[
PdCl(η -C H )] (P/Pd = 1/1) in DMSO-d according to the following P NMR spectra; for
3 5 2 6
1
G3[CO H]: –10.68 ppm, for palladium complex: 19.35 ppm. This downfield shift is similar to
2
that reported in the literature; Iwasawa, T.; Komano, T.; Tajima, A.; Tokunaga, M.; Obora, Y.;
Fujihara, T.; Tsuji, Y. Organometallics, 2006, 25, 4665–4669.
1
3. The dispersion system was stable within several minutes. Quick measurement (SEM) of this
system indicated that its particle size was 1 µm. Kobayashi et al. have also reported that Lewis
acid–surfactant-combined catalyst systems form colloidal dispersions (not micelles). Manabe,
K.; Mori, Y.; Wakabayashi, T.; Nagayama S.; Kobayashi, S. J. Am. Chem. Soc. 2000, 122,
7
202–7207.
3
14. By employing only [PdCl(
η -C H )] , which was not a dendritic catalyst, the catalytic reaction
3 5 2
did not proceed.
15. TPPTS: triphenylphosphine-3,3’,3’’-trisulfonic acid trisodium salt
1
6. Previously reported positive dendritic effects on chemical yields caused by the
periphery-catalyzed dendrimers: (a) Mansour, A.; Kehat, T.; Portnoy, M. Org. Biomol. Chem.,
2
008, 6, 3382–3387; (b) Dahan, A.; Portnoy, M. J. Am. Chem. Soc. 2007, 129, 5860–5869; c)
Benito, J. M.; de Jesus, E.; de la Mata, F. J.; Flores, J. C.; Gomez, R.; Chem. Commun. 2005,
5
217–5219; (d) Delort, E.; Darbre, T.; Reymond, J.-L. J. Am. Chem. Soc. 2004, 126,
1
5642–15643.
1
7. After the preparation of 1G3[H]–palladium complex in dichloromethane in situ, the
Suzuki–Miyaura reaction was carried out, followed by the replacement of dichloromethane by
water.
1
1
2
8. Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513
9. Hawker, C. J.; Fr chet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638
0. Hawker, C. J.; Wooley, K. L.; Fréchet, J. M. J. J. Chem. Soc., Perkin Trans. I 1993, 1287–1297.
–
519.
é
–
7647.
2
0

ACCEPTED MANUSCRIPT
1. Senear, A. E.; Valient, W.; Wirth, J. J. Org. Chem. 1960, 25, 2001–2006.
2
2
2. Manos-Turvey, A.; Watson, E. E.; Sykes, M. L.; Jones, A. J.; Baell, J. B.; Kaiser, M.; Avery, V.
M.; Payne, R. J. Med. Commun. 2015, 6, 403–406.
23. Yokoyama, N.; Nakayama, Y.; Nara, H.; Sayo, N. Adv. Synth. Catal. 2013, 355, 2083–2088.
2
1