Synthesis and reactivity profiles of phosphinated poly(alkyl aryl ether) dendrimers

Article abstract of DOI:10.1016/j.tet.2005.09.021

Poly(alkyl aryl ether) dendrimers were utilized to synthesize a series of new triphenylphosphine functionalized dendrimers. Zero, first, second and third generation dendrimers, carrying 3, 6, 12 and 24 triphenylphosphine units, were prepared and characterized. The new triphenylphosphine containing dendrimers were assessed for their reactivity profiles and in this instance, the dendrimers were used as reagents to mediate Mitsunobu etherification reaction between phenol and various primary, secondary and benzylic alcohols. In addition, dendritic poly-phenols were also tested in an O-benzylation reaction. A monomeric methoxy group attached triphenylphosphine acted as a control for comparison of reactivity profiles of dendrimers. It was observed that the etherification reaction was mediated efficiently by the dendritic reagent, and in addition, the dendritic phosphine oxide reagents could be recovered quantitatively by precipitation methods. The recovered dendritic phosphine oxides were reduced subsequently to the corresponding phosphines and used as reagents for the Mitsunobu reaction, repetitively.

Full text of DOI:10.1016/j.tet.2005.09.021

Tetrahedron 61 (2005) 11184–11191
Synthesis and reactivity profiles of phosphinated
poly(alkyl aryl ether) dendrimers
*
Jayaraj Nithyanandhan and Narayanaswamy Jayaraman
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Received 3 June 2005; revised 23 August 2005; accepted 8 September 2005
Available online 10 October 2005
Abstract—Poly(alkyl aryl ether) dendrimers were utilized to synthesize a series of new triphenylphosphine functionalized dendrimers. Zero,
first, second and third generation dendrimers, carrying 3, 6, 12 and 24 triphenylphosphine units, were prepared and characterized. The new
triphenylphosphine containing dendrimers were assessed for their reactivity profiles and in this instance, the dendrimers were used as
reagents to mediate Mitsunobu etherification reaction between phenol and various primary, secondary and benzylic alcohols. In addition,
dendritic poly-phenols were also tested in an O-benzylation reaction. A monomeric methoxy group attached triphenylphosphine acted as a
control for comparison of reactivity profiles of dendrimers. It was observed that the etherification reaction was mediated efficiently by the
dendritic reagent, and in addition, the dendritic phosphine oxide reagents could be recovered quantitatively by precipitation methods. The
recovered dendritic phosphine oxides were reduced subsequently to the corresponding phosphines and used as reagents for the Mitsunobu
reaction, repetitively.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
and the reaction kinetics and product selectivities are
comparable or better in comparison to the reactions
conducted with monomeric catalysts. Phosphination of
dendrimers provides an easy access to dendritic organo-
metallic complexes and various phosphinated dendrimers
and their metal complexes have thus been prepared and their
catalytic properties studied.5 We were interested in the
synthesis and studies of triphenylphosphine containing
dendrimers, in view of the manifold reactions known to
involve triphenylphosphine as a reagent, apart from its use
as a ligand for metal complexations. Here, we describe the
synthesis and an assessment of the reactivity profiles of a
series of triphenylphosphine containing dendrimers. One of
the phenyl groups of triphenylphosphine was involved for
covalent attachment at the peripheries of dendrimers and
dendrimers carrying 3, 6, 12 and 24 triphenylphosphine
units were thus installed at the peripheries of poly(alkyl aryl
ether) dendrimers. Following the preparation, these den-
drimers were assessed for their reactivity profiles as
reagents for Mitsunobu etherification reaction. Details of
synthesis and studies are presented herein.
Hyperbranched macromolecules with uniform branches at
every branching location are referred generally as dendritic
macromolecules. Ever since their prominence in the
literature,1 dendritic macromolecules have been explored
in detail as to their synthesis, physical and chemical
properties.2 Uniform branching throughout the structure is
one of the unique structural features of dendrimers. This
particular structural feature leads to uniform distribution of
chain ends within the molecule and it is of immediate
interest to find out whether this uniform distribution of chain
ends is beneficial for exploring the dendritic architectures
further in conjunction with other functional entities of
chemical, biological and material relevance. Thus, den-
drimers of various constitutions have been functionalized or
modified with different types of functional entities.2 The
evolution of the so-called ‘dendritic effect’ has been
observed in few instances, providing credibility to proper-
ties arising due to dendritic architecture.3 Organometallic
catalysis is one of the beneficiaries of dendritic structures
and many different organometallic complexes have been
synthesized and studied extensively.4 Dendritic catalysts
most often react under homogeneous reaction conditions
2. Results and discussion
2.1. Synthesis of triphenylphosphine functionalized
monomer
Keywords: Alkylation; Dendrimers; Etherification; Mitsunobu reaction;
Triphenyl phosphine.
*
Corresponding author. Tel.: C91 80 2293 2406/2403; fax: C91 80 2360
0529.; e-mail: jayaraman@orgchem.iisc.ernet.in
The dendrimers of choice for functionalization with
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.021

J. Nithyanandhan, N. Jayaraman / Tetrahedron 61 (2005) 11184–11191
11185
Scheme 1. (i) BnBr, K2CO3, 18-Crown-6 (cat.), Me2CO, reflux, 7 h, 89%; (ii) (a) Mg, I2 (cat.), THF, reflux, 1 h; (b) ClPPh2, THF, 0 8C to rt, 15 h, 60%; (iii)
30% H2O2, Me2CO, reflux, 1 h, 70%; (iv) Pd–C, EtOH, H2 (60 bar), 60 8C, 48 h, 72%. (v) 1,5-dibromopentane, K2CO3, 18-Crown-6 (cat.), DMF, 70 8C, 7 h,
86%.
triphenylphosphine moiety were the phloroglucinol based
poly(alkyl aryl ether) dendrimers, reported recently.6
Phenolic hydroxyl groups present at the peripheries of
these dendrimers were utilized to alkylate a phosphine oxide
containing monomer unit (6). The monomer 6 was obtained
by following a sequence of (i) O-benzylation of 4-bromo-
phenol (1) to afford 2; (ii) phosphination with chlorodiphe-
nyl phosphine to 3; (iii) oxidation of phosphine to phosphine
oxide (4); (iv) benzyl group deprotection to 5 and (v)
alkylation of 5 with dibromopentane to afford 6, in an
overall 23% yield (Scheme 1).
bromopentyloxy)benzene (7)6 led to the isolation of zero
generation triphenylphosphine oxide containing dendrimer
(8). O-Alkylations of first (G1-(OH)6) (10), second (G2-
(OH)12) (13) and third G3-(OH)24 (16) generation dendri-
mers with the monomer 6, in the presence of K2CO3 and 18-
C-6, afforded the corresponding 6 (11), 12 (14) and 24 (17)
phosphine oxide containing dendrimers, respectively
(Scheme 2). The phosphine oxide containing dendrimers
were purified (SiO2) and were obtained as glassy substances
soluble in common organic solvents. Reduction of the
phosphine oxide to phopshine was conducted using CeCl3/
LAH reagent system7 in THF (Scheme 2) and the reduction
reaction afforded the desired products in nearly quantitative
yields. The molecular structures of the phosphinated
dendrimers 9, 12, 15 and 18 are presented in Figures 1–3.
The phosphinated dendrimers were freely soluble in CHCl3,
CH2Cl2, THF and PhMe. In terms of loading, the
triphenylphosphine content was calculated to be 2.58,
2.15, 2.36 and 2.49 mmol/g for the zero (9), first (12),
second (15) and third (18) generation dendrimers,
respectively.
2.2. Synthesis of triphenylphosphine functionalized
dendrimer
A
three-fold O-alkylation of 5 with 1,3,5-tris(5-
2.3. Characterization
The purities of new synthesized dendrimers were examined
˚
by gel permeation chromatography (GPC) (Phenogel 500 A,
300!7.80 mm), eluting with THF (flow rate: 1 mL/min.,
UV–vis detector set at 254 nm). The GPC chromatograms
of each phosphine oxide functionalized dendrimers
Scheme 2. (i) K2CO3, 18-C-6 (cat.), DMF, reflux; (ii) CeCl3, LiAlH4, THF,
60 8C, 5 h.
Figure 1. Molecular structures of zero (9) and first (12) generation phopshinated poly(alkyl aryl ether) dendrimers.

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J. Nithyanandhan, N. Jayaraman / Tetrahedron 61 (2005) 11184–11191
Figure 2. Molecular structure of the second generation phopshinated dendrimer 15.
Figure 3. Molecular structure of third generation phosphinated dendrimer 18.

J. Nithyanandhan, N. Jayaraman / Tetrahedron 61 (2005) 11184–11191
11187
exhibited decreasing retention times centered at: 8:
9.31 min, 11: 8.26 min, 14: 7.75 min and 17: 7.58 min.
The phosphine oxide and the phosphinated dendrimers were
characterized by 1H, 13C, 31P NMR spectroscopies and
elemental composition analysis. Mass spectral characteriza-
tion was possible for the smaller molecular weight
compounds, that of larger molecular weight dendrimers,
ionizations by either FAB-MS or MALDI-TOF MS or ES-
MS were not successful. In the 1H NMR spectra, the
triphenylphosphine oxide unit appeared as multiplets
between 7.70 and 7.40 ppm, whereas in the corresponding
triphenylphosphine unit in dendrimers, the aromatic rings of
the phosphine unit appeared as multiplets between 7.30 and
7.20 ppm. The 31P NMR signals for the phosphine oxide and
phosphine moieties in all the compounds were observed at
29.0 and K7.0 ppm, respectively. Elemental composition
analyses confirmed further the constitution of each
compound.
Figure 4. Formation of n-butyl phenyl ether with dendritic phosphines.
The time course versus product formation was also
monitored by HPLC and the results are presented in
Figure 4, for the reaction between phenol and n-butanol,
mediated by DIAD and dendritic phosphines. The etheri-
fication involving these two substrates was facile with the
dendritic phosphines, as well as with the monomer 19.
Reaction mediated by PPh3 was also tested, however, the
product formation was sluggish with this reagent. In the case
of the dendritic phosphines and the monomer 19, the
reaction was almost complete within the first 15 min and
75–90% of the product formed within this period. In
comparison, PPh3 reaction required 90 min for 75%
formation of the product. Very similar reactivity profiles
of dendritic phosphines (9, 12, 15 and 18) and the
monomeric phosphine 19 indicate that each phosphine
unit on the dendritic scaffold act independently and in an
unconnected manner. Upon completion of the reaction,
solvents were removed and Et2O was added to the residue,
which solubilized the aryl ether product and the reduced
DIAD, leaving the phosphine oxide to be separated from the
solution. The Et2O solution was evaporated and the
resulting residue was added to petroleum ether, which
solubilized the aryl ether product, leaving the reduced
DIAD un-dissolved. In this manner, the aryl ether products
were obtained in excellent yields and purities, devoid of
reduced DIAD and phosphine oxide reagents. Further
purification by column chromatography was required in
order to remove un-reacted phenol and the alcohol.
2.4. Assessment of the reactivity profiles of the
phosphinated dendrimers
The reactivities of the phosphinated dendrimers were tested,
by involving them as a reagent in an etherification reaction,
namely, the Mitsunobu reaction.8 The reaction of phenol
with various alcohols was conducted using diisopropylazi-
dodicaboxylate (DIAD) and dendritic phosphines. The
Mitsunobu reaction is prominent in etherification and
esterification, in which phosphonium adduct formation
between DIAD and phosphine initiates the reaction, leading
to an ester or ether depending on the substrate. A systematic
mechanistic study has previously been performed9 on the
Mitsunobu reaction, as have reactions involving modified
phosphines and azidodicarboxylates.10 In the etherification
reaction performed herein, DIAD and dendritic phosphines
(1.1 M equiv, on per phosphine unit basis) were used with
respect to phenol and the alcohols (each 1 M equiv)
(Scheme 3). Results of the Mitsunobu reaction are presented
in Table 1. A good conversion of the alcohols to aryl ethers
was observed, for all the dendritic phosphines and the yields
were comparable to that of the monomer phosphine reagent,
namely, 4-methoxyphenyldiphenyl phosphine 19.11
The reactivities of the dendritic phosphines were also tested
in the alkylations of different generations of dendritic
phenols. Thus poly-benzylation of the phenolic hydroxyl
group functionalized poly(alkyl aryl ether) dendrimer was
performed in the presence of dendritic phosphines
(Scheme 4). 5-Benzyloxy resorcinol (20) and 19 were
used as monomeric analogs of phenol and phosphine,
respectively. Compounds, 10, 13 and 20 were thus
O-benzylated, by utilizing 9, 12 and 19 to afford tri-O-
benzylated phloroglucinol (21), G1-(OBn)6 (22) and G2-
(OBn)12 (23), respectively (Fig. 5). The time course versus
product formation was monitored by HPLC and the results
are presented in Table 2, for the reaction between poly-
phenols and benzyl alcohol, mediated by DIAD and the
dendritic/monomeric phosphines. Di-O-benzylation of
5-benzyloxy-resorcinol led to the isolation of the
Scheme 3. Phenol (1.0 M equiv), alcohol (1.0 M equiv), DIAD
(1.1 M equiv) and monomeric or dendritic phosphines 9, 12, 15 and 18
(1.1 M equiv on a per phosphine unit basis), CH2Cl2, room temperature.
Table 1. Mitsunobu etherification of phenol with different alcohols
Alcohol
n-Butanol
(% Yield)
2-Propanol
(% Yield)
Allyl
alcohol
(% Yield)
Benzyl
alcohol
(% Yield)
19
9
12
15
18
84
100
82
92
88
85
77
93
93
87
89
86
73
90
79
90
80
74
78
82

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J. Nithyanandhan, N. Jayaraman / Tetrahedron 61 (2005) 11184–11191
Scheme 4. (i) Dendritic phenol (1 M equiv) (10 or 13), triphenylphosphine (1.1 M equiv on per phosphine basis) (9 or 12), BnOH (1 M equiv), DIAD
(1.1 M equiv), THF, room temperature.
Figure 5. Molecular structures of monomeric (20), dendritic phenols (10 and 13) and their corresponding benzylated derivatives (21, 22 and 23).
Table 2. Polybenzyl ether formation with dendritic phosphines
Table 3. Percentage recovery of the phopshine oxide functionalized
dendrimers after each cycle of reduction and reuse of the resulting
phosphine in etherification reactions
Entry
Phenol
Phosphine
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
10
13
20
10
13
20
10
13
20
9
9
9
12
12
12
19
19
19
2.5
3.0
1.0
2.5
3.0
1.0
2.5
3.0
0.75
77
75
74
75
77
87
82
79
94
Dendrimer
Cycle
3
1
2
4
8
92
92
93
O95
Quant.
Quant.
93
95
Quant.
Quant.
11
14
17
O95
Quant.
Quant.
O95
Quant.
Quant.
reaction could be conducted several times, without any loss
in efficiency of the reactions (Table 3).
corresponding tri-O-benzylated phloroglucinol in good
yield within 45 min. Polybenzylation of 10 and 13 afforded
moderate yield (70–77%) of product in 3 h and prolonged
reaction time did not improve the yield.
3. Conclusion
After securing the triphenylphosphine oxide by the solvent
treatments (vide supra), reduction to the corresponding
triphenylphosphines was conducted using CeCl3/LAH, in
quantitative yield. The reduced reagents were used again for
the Mitsunobu reaction and the reaction could be conducted
efficiently as that of first cycle reagents. The oxidation of the
dendritic phosphine to mediate the etherification reaction,
the reduction of the resulting phosphine oxide to the
phosphine and subjecting the phosphine in the etherification
The scope and wide application of the Mitsunobu reaction is
well documented.8 The generic trialkyl and triaryl phos-
phines have led to the development of modified reagents,
which assist in simplifying the purification of the reaction
mixtures. Several modified phosphines, polymeric phos-
phines and fluorous phosphines have been developed to
make the Mitsunobu reaction a more versatile approach for
several etherification, esterification and amidation
reactions.10 The dendritic regents that we have presented

J. Nithyanandhan, N. Jayaraman / Tetrahedron 61 (2005) 11184–11191
11189
herein are a useful addition as a new types of triarylphos-
phine reagent.
EtOH (100 mL) was admixed with Pd–C (10%, 2.0 g),
stirred under H2 blanket (60 atm) at 60 8C in an autoclave
for 48 h. The reaction mixture was filtered, concentrated and
dried in vacuo to afford 5 as a white solid (11.1 g, 72%).
TLC: Rf 0.27 (PhMe/EtOAcZ7:3). Mp: 240 8C. IR (KBr,
4. Experimental
1
cmK1): 3437.5; H NMR (CDCl3, 300 MHz) d: 6.94 (dd,
4
4.1. General remarks
3JHHZ8.7 Hz, JPHZ2.1 Hz, 2H), 7.40–7.67 (m, 12H),
10.08 (s, 1H); 13C NMR (CDCl3, 75.5 MHz) d: 115.3 (d, JZ
13.6 Hz), 127.8 (d, JZ12.1 Hz), 131.3 (d, JZ10.6 Hz),
131.6, 133.0, 133.3 (d, JZ10.6 Hz), 160.7; 31P{1H} NMR
(CDCl3, 162 MHz) d: 29.8; HR-MS m/z: calcd for
C18H15O2P [MC1]C: 295.0888; found: 295.0874 (100%).
Anal. Calcd for C18H15O2P: C, 73.46; H, 5.14; found: C,
73.35; H, 5.25.
4.1.1. Compound 2. To a solution of 4-bromophenol
(25.0 g, 144.4 mmol) in Me2CO (100 mL), BnBr (24.71 g,
144.5 mmol), K2CO3 (19.9 g, 144.5 mmol), 18-C-6 (cat.)
were added and refluxed for 7 h. The reaction mixture was
filtered, solvents removed in vacuo, the resulting residue
dissolved in CHCl3 (150 mL), washed with water (2!
150 mL), the organic portion dried (Na2SO4) and concen-
trated to afford 2, as a white solid (34.0 g, 89%). TLC: Rf
0.65 (Hexane/EtOAcZ98:2). Mp: 59–60 8C. 1H NMR
(300 MHz, CDCl3) d: 4.99 (s, 2H), 6.83 (d, JZ6.9 Hz,
2H), 7.34–7.38 (m, 7H); 13C NMR (75.5 MHz, CDCl3) d:
70.1, 113.1, 116.6, 127.4, 128.1, 128.6, 132.2, 136.5, 157.8.
Anal. Calcd for C13H11BrO: C, 59.34; H, 4.21; found: C,
59.46; H, 4.35.
4.1.5. Compound 6. To a solution of 5 (10.0 g, 34.01 mmol)
in DMF (25 mL), 1,5-dibromopentane (23.0 g, 102 mmol),
K2CO3 (5.64 g, 40 mmol) and 18-crown-6 (cat.) were added
and stirred at 70 8C for 7 h. Solvents were removed in vacuo
and the resulting crude mixture dissolved in CHCl3
(100 mL), washed with H2O (2!100 mL), dried (Na2SO4),
concentrated and purified (SiO2) to afford 6, as a brown oil
(12.9 g, 86%). TLC: Rf 0.38 (PhMe/EtOAcZ1:1). 1H NMR
(CDCl3, 300 MHz) d: 1.62 (m, 2H), 1.78 (m, 2H), 1.93 (m,
2H), 3.43 (t, JZ6.6 Hz, 2H), 4.00 (t, JZ6.0 Hz, 2H), 6.95
4.1.2. Compound 3. To a suspension of Mg (1.01 g,
41.65 mmol) in THF (7 mL) and I2 (25 mg), 2 (10.0 g,
37.9 mmol) in THF (20 mL) was added dropwise, refluxed
for 1 h and cooled to 0 8C. Chlorodiphenyl phosphine
(9.61 g, 43.6 mmol) in THF (5 mL) was added over a period
of 10 min and stirred for 15 h at room temperature. The
reaction mixture was quenched with aq. HCl (5%), washed
with CHCl3 (200 mL), followed by H2O (2!100 mL), dried
(Na2SO4), concentrated and purified to afford phosphine, 3,
as a colorless solid (8.4 g, 60%). TLC: Rf 0.72 (PhMe). Mp:
48–50 8C. 1H NMR (300 MHz, CDCl3) d: 4.99 (s, 2H), 6.93
(d, JZ7.5 Hz, 2H), 7.23–7.39 (m, 17H); 13C NMR
(75.5 MHz, CDCl3) d: 69.8, 115.0 (d, JZ6.8 Hz), 127.42,
127.9 (d, JZ9.8 Hz), 128.4 (d, JZ7.6 Hz), 128.5, 129.4,
133.4 (d, JZ18.1 Hz), 135.5 (d, JZ21.1 Hz), 136.6, 137.8
(d, JZ11.3 Hz), 158.7, 159.5; 31P{1H} NMR (162 MHz,
CDCl3) d: K7.0; HR-MS m/z: calcd for C25H21OP
[MC1]C: 369.1408; found: 369.1413 (50%). Anal. Calcd
for C25H21OP: C, 81.5; H, 5.75; found: C, 81.42; H, 5.96.
3
(d, JHHZ7.5 Hz, 2H), 7.45–7.69 (m, 12H); 13C NMR
(CDCl3, 75.5 MHz) d: 24.7, 28.2, 32.3, 33.5, 67.6, 114.5
(d, JZ13.0 Hz), 128.4 (d, JZ11.9 Hz), 131.8, 132.0 (d,
JZ10.0 Hz), 133.4, 133.9 (d, JZ11.2 Hz), 162.0; 31P{1H}
NMR (CDCl3, 162 MHz) d: 28.0; HR-MS m/z: calcd for
C23H24BrO2P [MCNa]C: 465.0595; found: 465.0595
[MCNa]C(100%), 467.0618 [MCNaC2]C(98%). Anal.
Calcd for C23H24BrO2P: C, 62.31; H, 5.46; found: C, 61.91;
H, 5.57.
4.1.6. Compound 8. A mixture of 76 (0.41 g, 0.71 mmol), 5
(0.75 g, 2.55 mmol), K2CO3 (0.15 g, 1.1 mmol) and 18-
crown-6 (cat.) in DMF (20 mL) was stirred at 70 8C for 12 h.
Solvents were then removed in vacuo, the resulting residue
dissolved in CH2Cl2, washed with water, dried, concen-
trated and purified (SiO2, CHCl3/MeOHZ95:5) to afford 8,
as colorless oil (0.9 g, 92%). TLC: Rf 0.59 (CHCl3/MeOHZ
96:4). 1H NMR (300 MHz, CDCl3) d: 1.62 (m, 6H), 1.86 (m,
12H), 3.93 (t, JZ6.3 Hz, 6H), 4.01 (t, JZ6.0 Hz, 6H), 6.07
4.1.3. Compound 4. Aq. H2O2 (30%) (3.33 g, 97.8 mmol)
was added cautiously to an ice-cooled solution of 3 (18.0 g,
48.9 mmol) in Me2CO (75 mL) and refluxed for 1 h. The
solvent was removed in vacuo. PhMe (100 mL) and aq.
NaOH (10%, 70 mL) were added to the resulting residue
and stirred for 1 h at room temperature. The organic layer
was separated, washed with brine (2!150 mL), dried
(Na2SO4), concentrated. Upon addition of Et2O (70 mL),
4 precipitated, as a white solid (13.2 g, 70%). TLC: Rf 0.5
3
4
(s, 3H), 6.95 (dd, JHHZ8.7 Hz, JPHZ1.8 Hz, 6H), 7.42–
7.69 (m, 36H); 13C NMR (75.5 MHz, CDCl3) d: 22.7, 28.8,
28.9, 67.7, 67.9, 93.8, 114.5 (d, JZ12.8 Hz), 128.4 (d, JZ
11.3 Hz), 131.8, 132.0 (d, JZ9.8 Hz), 132.2, 133.6, 133.9
(d, JZ11.3 Hz), 160.9, 161.9, 162.0; 31P{1H} NMR
(CDCl3, 162.0 MHz) d: 29.4; MALDI-TOF-MS m/z: calcd
for C75H75O9P3: 1213; found: 1213 [M]C(15%), 1235.5
[MCNa]C(100%), 1251.6 [MCK]C(70%). Anal. Calcd for
C75H75O9P3: C, 74.24; H, 6.23; found: C, 73.77; H, 7.1.
1
(EtOAc/PhMeZ7:3). Mp: 121–122 8C. H NMR (CDCl3,
300 MHz) d: 5.06 (s, 2H), 7.02 (d, JZ6.9 Hz, 2H), 7.26–
7.69 (m, 17H); 13C NMR (CDCl3, 75.5 MHz) d: 69.8, 114.7
(d, JZ12.9 Hz), 127.2, 127.9, 128.2 (d, JZ11.9 Hz), 128.4,
131.6, 131.8 (d, JZ9.9 Hz), 133.7 (d, JZ11.2 Hz), 135.9,
161.5; 31P{1H} NMR (CDCl3, 162 MHz,) d: 27.8; HR-MS
m/z: calcd for C25H21O2P [MC1]C: 385.1357; found:
385.1364 (100%). Anal. Calcd for C25H21O2P: C, 78.11; H,
5.51; found: C, 78.02; H, 5.59.
4.1.7. Compound 9. To a stirred suspension of CeCl3
(0.29 g, 1.16 mmol) in THF (6 mL), LiAlH4 (0.059 g,
1.55 mmol) and 8 (0.312 g, 0.26 mmol) in THF (3 mL)
were added and warmed at 60 8C for 4 h. The reaction
mixture was quenched with water, filtered, concentrated and
purified by passing through a pad of SiO2 (2% EtOAc/
PhMe) to afford compound 9, as colorless oil (0.3 g, 98%).
1
TLC Rf 0.65 (PhMe/EtOAcZ98:2). H NMR (300 MHz,
CDCl3) d: 1.63 (m, 6H), 1.83 (m, 12H), 3.95 (m, 12H), 6.06
4.1.4. Compound 5. A solution of 4 (20 g, 52.1 mmol) in

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J. Nithyanandhan, N. Jayaraman / Tetrahedron 61 (2005) 11184–11191
(s, 3H), 6.87 (d, JZ7.8 Hz, 6H), 7.23–7.30 (m, 36H);
13C NMR (75.5 MHz, CDCl3) d: 22.7, 28.9, 67.6, 67.7, 93.8,
114.7 (d, JZ7.6 Hz), 128.4 (d, JZ7.6 Hz), 133.4 (d, JZ
19.6 Hz), 135.6 (d, JZ21.1 Hz), 137.9 (d, JZ9.8 Hz)
159.8, 160.8; 31P{1H} NMR (CDCl3, 162.0 MHz) d:
K6.9. Anal. Calcd for C75H75O6P3: C, 77.3; H, 6.49;
found: C, 77.2, H, 6.51.
C381H408O54P12: C, 73.54; H, 6.61; found: C, 73.43; H,
7.12.
4.1.11. Compound 15. To a stirred suspension of CeCl3
(0.086 g, 0.35 mmol) in THF (6 mL), LAH (0.025 g,
0.69 mmol) was added and stirred for 1 h at room
temperature. Dendrimer 14 (0.12 g, 0.019 mmol) in THF
(5 mL) was added and refluxed at 60 8C for 5 h. The reaction
mixture was quenched with water, filtered and concentrated.
The crude product was purified by passing through a pad of
SiO2 (5% EtOAc/PhMe) to afford 15, as a colorless oil.
4.1.8. Compound 11. A mixture of 106 (0.22 g, 0.31 mmol),
6 (1.0 g, 2.25 mmol), K2CO3 (0.311 g, 2.25 mmol) and 18-
crown-6 (cat.) in DMF (10 mL) was heated at 70 8C for
48 h. Solvents were then removed in vacuo and the resulting
residue was dissolved in CH2Cl2, washed with water, dried
(Na2SO4) and concentrated. Excess of 6 was removed by
triturating with Et2O washings and the residue was purified
further (SiO2, CHCl3/MeOHZ95:5) to afford 11, as a
brown foamy material (0.69 g, 76%). TLC Rf 0.52 (CHCl3/
1
TLC: Rf 0.41 (PhMe/EtOAcZ98:2). H NMR (300 MHz,
CDCl3) d: 1.62 (br, 42H), 1.83 (br, 84H), 3.93 (m, 84H),
6.06 (s, 30H), 6.94 (d, JZ8.4 Hz, 24H), 7.23–7.67 (br,
144H); 13C NMR (75.5 MHz, CDCl3) d: 22.7, 29.0, 29.7,
67.6, 67.7, 93.8, 114.7 (d, JZ7.6 Hz), 128.4 (d, JZ7.6 Hz),
133.4 (d, JZ15.9 Hz), 133.5, 135.6 (d, JZ21.1 Hz), 137.9
(d, JZ10.6 Hz), 159.9, 160.9; 31P{1H} NMR (CDCl3,
162.0 MHz) d: K7.0. Anal. Calcd for C381H408O42P12: C,
75.88; H, 6.82; found: C, 75.84; H, 6.54.
1
MeOHZ96:4). H NMR (300 MHz, CDCl3) d: 1.62 (br,
18H), 1.82 (br, 36H), 3.92 (br, 24H), 4.01 (t, JZ5.7 Hz,
12H), 6.06 (s, 12H), 6.94 (dd, 3JHHZ8.4 Hz, 4JPHZ1.8 Hz,
12H), 7.44–7.67 (m, 72H); 13C NMR (75.5 MHz, CDCl3) d:
22.6, 28.7, 28.8, 28.9, 67.6, 67.7, 93.7, 114.4 (d, JZ
13.1 Hz), 128.3 (d, JZ11.8 Hz), 131.7, 131.8, 131.9 (d, JZ
10.0 Hz), 132.2, 133.5, 133.8 (d, JZ11.9 Hz), 160.7, 161.9;
31P{1H} NMR (CDCl3, 162.0 MHz) d: 28.0; ES-MS m/z:
calcd for C177H186O24P6: 2883.2; found: 1442.2
[M]2C(93%). Anal. Calcd for C177H186O24P6$3H2O: C,
72.32; H, 6.54; found: C, 72.36; H, 7.01.
4.1.12. Compound 17. A mixture of 166 (0.058 g,
0.014 mmol), 6 (0.183 g, 0.414 mmol), K2CO3 (0.046 g,
0.33 mmol) and 18-crown-6 (cat.) in DMF (15 mL) was
heated at 70 8C for 6 days. Solvents were removed in vacuo
and the resulting residue was dissolved in CH2Cl2, washed
with water, dried (Na2SO4) and concentrated. Excess 6 was
removed by triturating with Et2O and the residue was
purified further (SiO2, EtOAc/MeOHZ95/5) to afford 17 as
a brown oil (0.098 g, 55%). TLC Rf 0.42 (CHCl3/MeOHZ
1
4.1.9. Compound 12. To a stirred suspension of CeCl3
(0.20 g, 0.82 mmol) in THF (6 mL), LiAlH4 (0.041 g,
1.08 mmol) was added and stirred for 1 h at room
temperature. A solution of 11 (0.26 g, 0.09 mmol) in THF
(5 mL) was added and refluxed at 60 8C for 5 h. The reaction
mixture was quenched with water, filtered and concentrated.
The crude reaction mixture was purified by passing through
a pad of SiO2 (2% EtOAc/PhMe) to afford 12, as a colorless
95:5). H NMR (300 MHz, CDCl3) d: 1.57 (br, 90H), 1.81
(br, 180H), 3.71–4.12 (br, 180H), 6.04 (s, 66H), 6.95 (dd,
4
3JHHZ8.4 Hz, JPHZ1.8 Hz, 48H), 7.42–7.69 (br, 288H);
13C NMR (75.5 MHz, CDCl3) d: 22.6, 28.7, 29.0, 67.8, 68.0,
93.9, 114.6 (d, JZ13.6 Hz), 128.3, 128.4 (d, JZ12.1 Hz),
129.1, 131.8, 132.0 (d, JZ9.8 Hz), 134.0 (d, JZ11.3 Hz),
160.9, 161.8; 31P{1H} NMR (CDCl3, 162.0 MHz) d: 29.3.
Anal. Calcd for C789H852O114P24: C, 73.45; H, 6.66; found:
73.23; H, 7.11.
1
oil (0.24 g, 96%). TLC Rf 0.58 (PhMe/EtOAcZ98:2). H
NMR (300 MHz, CDCl3) d: 1.61 (m, 18H), 1.85 (m, 36H),
3.99 (m, 36H), 6.07 (s, 12H), 6.88 (d, JZ6.3 Hz, 12H),
7.25–7.32 (m, 72H); 13C NMR (75.5 MHz, CDCl3) d: 22.7,
25.6, 28.9, 67.7, 67.9, 93.8, 114.7 (d, JZ7.6 Hz), 128.4 (d,
JZ7.6 Hz), 133.4 (d, JZ19.6 Hz), 135.6 (d, JZ21.1 Hz),
137.8, 159.8, 160.9; 31P{1H} NMR (CDCl3, 162.0 MHz) d:
K7.0. Anal. Calcd for C177H186O18P6: C, 76.27; H, 6.73;
found: C, 76.02, H, 6.51.
4.1.13. Compound 18. To a stirred solution of 17 (47 mg,
0.006 mmol), CeCl3 (0.033 g, 0.131 mmol) in THF (4 mL)/
DMF (0.1 mL), LAH (0.075 g, 1.97 mmol) was added and
refluxed for 24 h. The reaction mixture was quenched with
water, filtered, concentrated and dried. The crude product
was purified by passing through a pad of SiO2 (10% EtOAc/
PhMe) to afford 18, as a brown oil (0.038 g, 84%). TLC: Rf
1
0.30 (PhMe/EtOAcZ90:10). H NMR (300 MHz, CDCl3)
4.1.10. Compound 14. A mixture of 136 (0.2 g, 0.11 mmol),
6 (0.68 g, 1.54 mmol), K2CO3 (0.212 g, 1.53 mmol) and 18-
C-6 (cat.) in DMF (10 mL) was heated at 70 8C for 72 h.
Solvents were then removed in vacuo and the resulting
residue was dissolved in CH2Cl2, washed with water, dried
(Na2SO4), concentrated and purified (SiO2, CHCl3/
MeOHZ8:2) to afford 14, as a brown oil (0.45 g, 68%).
d: 1.57 (br, 90H), 1.83 (br, 180H), 3.94 (m, 180H), 6.05
(s, 66H), 6.87 (d, JZ8.1 Hz, 48H), 7.23–7.30 (br, 288H);
13C NMR (75.5 MHz, CDCl3) d: 22.8, 29.0, 29.7, 67.7, 67.8,
93.8, 114.7 (d, JZ7.6 Hz), 128.4 (d, JZ7.6 Hz), 133.4 (d,
JZ19.6 Hz), 135.6 (d, JZ21.1 Hz), 137.9, 159.9, 160.9;
31P{1H} NMR (CDCl3, 162.0 MHz) d: K7.0. Anal. Calcd
for C789H852O90P24: C, 75.7; H, 6.86; found: C, 75.29; H,
6.52.
1
TLC Rf 0.47 (CHCl3/MeOHZ92:8). H NMR (300 MHz,
CDCl3) d: 1.65 (br, 42H), 1.81 (br, 84H), 3.91 (br, 60H),
3
3.97 (t, JZ6.6 Hz, 24H), 6.05 (s, 30H), 6.93 (d, JHH
Z
4.2. General procedure for the alkyl aryl ether formation
8.4 Hz, 24H), 7.43–7.68 (br, 144H); 13C NMR (75.5 MHz,
CDCl3) d: 22.0, 22.7, 28.8, 29.0, 67.8, 67.9, 68.0, 93.4,
114.6 (d, JZ13.6 Hz), 128.5 (d, JZ12.1 Hz), 129.3, 131.9,
132.1 (d, JZ9.8 Hz), 134.0 (d, JZ11.3 Hz), 160.9, 162.1;
31P{1H} NMR (CDCl3, 162.0 MHz) d: 29.3. Anal. Calcd for
To
a solution of phenol (1.0 M equiv), alcohol
(1.0 M equiv) and phosphine (1.1 M equiv on per phosphine
unit basis) in CH2Cl2 (1.5 mL), DIAD (1.1 M equiv) was
added and the reaction mixture was stirred at room

J. Nithyanandhan, N. Jayaraman / Tetrahedron 61 (2005) 11184–11191
11191
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temperature for 1 h, under N2 atmosphere. Solvents were
removed in vacuo and Et2O was added to precipitate the
phosphine oxide. Et2O portion was separated, concentrated
and the resulting residue was added with petroleum ether.
Petroleum ether portion was filtered from un-dissolved
reduced DIAD and solvents were removed in vacuo and
purified further. For monitoring the reaction, an aliquot of
petroleum ether was injected into a normal phase (SiO2)
semi-preparative column, attached to a HPLC. Elution was
carried out with EtOAc/pet. ether (3:1), at a rate of 1 mL/min.
and monitored at 254 nm. The retention times for the start-
ing materials and products were, benzyl alcohol: 22.5 min;
phenol: 17.4 min; phenyl butyl ether: 16.4 min; phenyl
isopropyl ether: 16.5 min; phenyl allyl ether: 16.7 min;
phenyl benzyl ether: 16.0 min.
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Acknowledgements
We are grateful to Council of Scientific and Industrial
Research (CSIR), New Delhi, for financial support. J.N.
thanks CSIR for a research fellowship.
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