Fast and scalable route to aryl polyallyl dendrons and dendrimers

Article abstract of DOI:10.1002/adsc.200800163

In the quest for general and efficient synthetic procedures for dendrons and dendrimers, allylphenol, allylnaphthol and 6-bromonaphthalene AB₃ dendrons have been successfully prepared on a large-scale by a rapid and clean route starting from commercially available esters and allyl bromide. In contrast to the known organoiron strategy, the above-mentioned methodology enables the large-scale synthesis of AB₃ dendrons in only two days.

Full text of DOI:10.1002/adsc.200800163

UPDATES
DOI: 10.1002/adsc.200800163
Fast and Scalable Route to Aryl Polyallyl Dendrons and
Dendrimers
Sylvain Nlate,a,* Lauriane Plault,a FranÅois-Xavier Felpin,b and Didier Astruca
a
UniversitØ BordeauxI, CNRS, ISM, UMR No. 5255, Nanosciences and Catalysis Group, 351 Cours de la LibØration,
33405 Talence Cedex, France
Fax: ( +33)-54000-6994; e-mail: s.nlate@ism.u-bordeaux1.fr
UniversitØ BordeauxI, CNRS, ISM, UMR No. 5255, Synthesis of Bioactive Molecules Group, 351 Cours de la LibØration,
b
33405 Talence Cedex, France
Received: March 17, 2008; Published online: May 16, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: In the quest for general and efficient syn-
thetic procedures for dendrons and dendrimers, al-
lylphenol, allylnaphthol and 6-bromonaphthalene
AB3 dendrons have been successfully prepared on a
large-scale by a rapid and clean route starting from
commercially available esters and allyl bromide. In
contrast to the known organoiron strategy, the
above-mentioned methodology enables the large-
scale synthesis of AB3 dendrons in only two days.
cation CpFe+: the enhanced acidity of the benzylic
protons and the nucleophilic cleavage of the O-alkyl
bond of phenyl ether complexes. Thus, they have
shown that the perfunctionalization and heterolytic
cleavage of the O-alkyl bond of phenyl ether complex
1c in a one-pot reaction, nine sequence, directly lead
to a dendron.[11] The 4-triallylmethylphenol dendron 2
has been synthesized following this route, from the
ferrocene complex 1a, in 10 days, with an overall
yield of 25%, as outlined in Scheme 1.
Keywords: AB3 dendrons; allylcarbinol; aryl polyal-
lyl dendrons/dendrimers; dendrimers
Introduction
The construction of organic, inorganic and organome-
tallic dendrimers is now a well-established field of re-
search.[1] Publications from the last few years demon-
strate a continuing interest in the development of new
and ever more efficient synthetic methodologies,[2]
and a considerable number of dendritic compounds
have been prepared for industrial applications[3] as
well as academic studies[4]. Because of their con-
trolled molecular architectures, dendrimers have
found use in various areas such as catalysis,[5] supra-
molecular chemistry,[6] biomimetics,[7] surface chemis-
Scheme 1. Organometallic one-pot route to 4-triallylmethyl-
phenol dendron (2).[11]
try,[8] light-harvesting materials,[9] and medicine.[10]
A
number of useful methods for the synthesis of den-
drimers have been reported. Among these, the tem-
In spite of the difficulty to prepare the AB3 den-
porary complexation of aromatics by 12-electron or- dron 2, the latter remains an interesting starting mate-
ganotransition metal units provides a powerful means rial for the fast synthesis of dendrimers. Indeed, this
to activate aromatics towards nucleophilic and depro- dendron has several advantages: (i) it can be function-
tonation reactions.[11] In this context, Astruc et al., alized at both the phenolic and allylic positions;[12] (ii)
have developed an original way to prepare dendrim- it allows a rapid dendritic growth for the construction
ers and dendrons, using a synergy between two modes of giant dendrimers[13] with a very high number of
of aromatic activation by the electron-withdrawing branches, since the number of branches is multiplied
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Sylvain Nlate et al.
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by three for each new generation of dendrimer; (iii) it on procedure outlined in Scheme 1 for the synthesis
can be bound, after suitable elaboration of functional- of 4-triallylmethylphenol (2), our synthetic route,
ities, to nanoparticles,[14] surfaces and polymers[8] (con- which consists of a three-step sequence, brings signifi-
vergent synthesis), as well as star and dendritic cores cant improvements, such as lower cost, lower overall
(divergent method). For example, the use of this tri- reaction time (2 vs. 10 days) and better overall yield
podal dendron in our laboratory has shown its broad (87 vs. 25%).
synthetic potential for the fast divergent and conver-
gent synthesis of polyallyl dendrons, dendrimers and
metallodendrimers.[11,12] However, the only procedure Results and Discussion
reported so far for the synthesis of the phenol den-
dron 2 is the above-mentioned organoiron method. In The organic approach to the large-scale synthesis of
spite of remarkable improvements of the organoiron 4-triallylmethylphenol dendron (2) starting from the
procedure in recent years, its use was still compro- commercially available methyl 4-methoxybenzoate
mised by several restrictions, especially the modest (2a) is summarized in Scheme 2.
yield (25%) and the length of the overall synthetic
procedure. On the other hand, AB3 dendrons are very carbinol
The first step involved the synthesis of diallylated
4-(4-methoxyphenyl)-hepta-1,6-dien-4-ol
attractive for industrial and academic chemists as they (2b), prepared from methyl 4-methoxybenzoate (2a)
allow a rapid dendritic structure growth and are often and allylmagnesium bromide at 08C.[16] The mixture
used to functionalize molecular and nanoscale materi- of both reagents in diethyl ether showed a rapid
als.[15] Thus, a concise and clean route for the large- colour change from green to white, yielding the diallyl
scale synthesis of such dendrons is necessary. Ideally, 4-(4-methoxyphenyl)-hepta-1,6-dien-4-ol (2b) as a col-
the syntheses would require only very few steps, use ourless oil in 95% yield after column chromatography
precursors that are inexpensive, and be amenable to purification.
application on a large scale. Furthermore, it would be
In the second step, the allylation by allyltrimethylsi-
advantageous if the method could be applied to the lane of the carbenium ion generated in the ionization
synthesis of new aromatic AB3 dendrons.
process of diallylcarbinol 2b with boron trifluoride at
Herein, we describe a fast and efficient protocol for À788C,[17] leads to 4-methoxytriallylmethylbenzene in
a large-scale synthesis of 4-triallylmethylphenol den- 95% yield. Our experiments to find the optimal con-
dron 2 starting from the commercially available ditions have shown that the success of this reaction is
methyl 4-methoxybenzoate 2a (Scheme 2). In order to highly temperature dependent. While only 26% of 2c
generalize the usefulness of this procedure to aryl de- was isolated at 208C, decreasing the reaction temper-
rivatives, naphthalene AB3 dendrons – 6-triallylmeth- ature to À788C led to 95% of the triallylated product.
yl-2-naphthol (3) and 6-bromo-2-triallylmethylnaph-
The last step consists of the deprotection of the
thalene (4) have also been prepared, starting from phenol group in 2c using the reported (n-Bu)4NI/BCl3
readily available ethyl 4-methoxynaphthoate (3a), and system.[18] When the protected 4-methoxytriallylme-
methyl 6-bromo-2-naphthoate (4a) respectively thylbenzene (2c) was treated with tetrabutylammoni-
(Scheme 3 and Scheme 4). Compared to the organoir- um iodide and boron trichloride from À788C to room
Scheme 2. Organic approach to 4-triallylmethylphenol dendron (2).
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Fast and Scalable Route to Aryl Polyallyl Dendrons and Dendrimers
UPDATES
Scheme 3. Synthesis of dendron 6-triallylmethyl-2-naphthol (3).
6-triallylmethyl-2-naphthol (3) has been successfully
obtained in three steps, starting from the ethyl 6-me-
thoxy-2-naphthoate (3a) and allylmagnesium bromide
(Scheme 3).
In analogy to 2b, the first step involved the synthe-
sis of diallylcarbinols – 4-(6-methoxynaphthyl)-hepta-
1,6-dien-4-ol (3b) obtained in 95% from the corre-
sponding naphthoate and allylmagnesium bromide.
The allylation of the readily ionizable 3b with allyltri-
methylsilane in a solution of BF3 in dichloromethane
gave the naphthol protected 6-methoxy-2-triallylme-
thylnaphthalene 3c in 90% yield. The deprotection of
the phenol group in 3c in the presence of (n-Bu)4NI/
[18]
BCl3 led to the 6-triallylmethyl-2-naphthol dendron
(3) in 92% yield.
This procedure was also applied to the direct syn-
thesis of the aryl halide AB3 dendron in two steps, as
outlined in Scheme 4. Thus, the allylation of methyl 6-
bromo-2-naphthoate 4a with allylmagnesium bromide,
as described for 2a, gives the double allylated com-
pound 4-(6-bromonaphthyl)-hepta-1,6-dien-4-ol (4b)
in 94% yield. The latter in the presence of allyltrime-
thylsilane and the BF3/CH2Cl2 system, leads to the
Scheme 4. Synthesis of 6-bromo-2-triallylmethylnaphthalene
dendron (4).
temperature, the 4-triallylmethylphenol dendron 2 formation of 6-bromo-2-triallylmethylnaphthalene
was obtained as a colourless oil in 96% yield after dendron 4 in 80% yield.
column chromatographic purification. The reaction is
The evaluation of the synthetic performance of
followed by the complete disappearance of the halide substituted AB3 arene dendrons such as 4 in
1H NMR signal (3.80 ppm) indicative of the methoxy C C coupling reactions is being investigated in our
group of 2c. Initial attempts to prepare 2 on a large group. Indeed, their use in C C bond coupling reac-
À
À
scale (using up to 40 g of 2a) led to comparable tions constitutes a challenging approach for the direct
yields.
functionalization of functional molecules and den-
The above-mentioned synthetic approach was also
In order to evaluate the efficiency of this procedure drimers with dendrons.
and to generalize its usefulness to aromatic com-
pounds, naphthalene AB3 dendrons have been pre- applied to the direct synthesis of dendritic cores.
pared. Thus, following the same protocol, the dendron Thus, hexa- and nonaallyl dendritic cores 5 and 6[19]
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Sylvain Nlate et al.
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Scheme 5. Organic approach to the hexaallyl 5 and nonaallyl 6 dendritic cores.[19]
were synthesized in two steps from the corresponding commercially or readily available starting materials.
aryl di- and triesters (Scheme 5). This protocol has been successfully applied to the
In the first step, allylmagnesium bromide reacts direct synthesis of allylic dendritic cores, and appears
with commercially available diethyl terephthalate (5a) as a significantly more efficient, less expensive and
and triethyl 1,3,5-benzenetricarboxylate (6a) affording time-consuming alternative to the organoiron route
the desired tetraallyl dicarbinol 5b and hexaallyltricar- used previously to access such compounds. We believe
binol 6b in 95 and 94% yields, respectively. The allyla- that this method should be valuable for the rapid syn-
tion of carbinols 5b and 6b with allyltrimethylsilane in thesis of new functionalized dendrons, and conse-
the presence of BF3, from À788C to room tempera- quently, for the rapid growth of various higher gener-
ture afforded the hexaallyl 5 and nonaallyl dendri- ation dendrimers. The evaluation of the synthetic per-
A
rapid colour change of the mixture to orange ob- ticated dendrons and dendrimers is being investigated
served with 2, 3 and 4, indicative of reaction efficien- in our group.
cy at À788C, was not observed. However, the orange
colour slowly appeared with the increase of the reac-
tion temperature. These low yields in the allylation of Experimental Section
di- and tricarbinol might be assigned to the competing
processes arising from the carbenium ion-mediated General Procedure for the Synthesis of Allylcarbinol
dimerization or polymerization.[17] Analytical data of Compounds
5 and 6 are consistent with the proposed structures,
Under an inert atmosphere,
a solution of aryl ester
and are similar to those reported when using the or-
ganoiron protocol.[19] It is interesting to note that, in
spite of the modest yields for the second step of this
novel procedure, substantial quantities of up to 5.5 g
and 3.7 g have been obtained respectively for 5 and 6.
Overall, the strategy reported in this manuscript rep-
resents a rapid, efficient and inexpensive procedure
for the large scale preparation of 5 and 6.
(55.5 mmol) in 20 mL diethyl ether cooled at 08C, was
added to a Schlenk tube with 1 M allylmagnesium bromide
solution in diethyl ether (138 mmol, 138 mL) at 08C. The
green colour of the reaction mixture changed immediately
and a white precipitate was formed. After 5 min stirring, a
solution of 6 M NH4Cl (100 mL) was added to the reaction
mixture, and the product was extracted with diethyl ether
(3”40 mL), and dried over Na2SO4. The solvent was re-
moved under vacuum and the product purified by chroma-
tography on a silica gel column.
Conclusions
General Procedure for the Allylation of Allylcarbinol
Compounds
We have shown that allylic AB3 phenyl or naphthyl
dendrons can be obtained in large-scale reactions in
In a Schlenk tube, to a solution of allyltrimethylsilane
good to excellent yields, via a new procedure using (250 mmol, 39.5.4 mL) in 40 mL CH2Cl2, cooled to À788C,
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Fast and Scalable Route to Aryl Polyallyl Dendrons and Dendrimers
UPDATES
was added a solution of 1 M BF3 in Et2O (250 mmol,
250 mL). Then, a CH2Cl2 (40 mL) solution of allylcarbinol
(50 mmol) also cooled to À788C was added to the reaction
nek, D. F. Shantz, Chem. Mater. 2006, 18, 2935; d) N.
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mixture. The colourless mixture changed immediately to
orange. After 5 min stirring, the cooling bath was removed
and the solvent evaporated under vacuum. Then, 50 mL of
Et2O and 50 mL of H2O were added. The product was ex-
tracted with Et2O (40 mL”2) and dried over Na2SO4. The
solvent was removed under vacuum and the product puri-
fied by chromatography on a silica gel column with a pen-
tane/diethyl ether eluent mixture. The rapid orange colour
change of the mixture that expressed the reaction efficiency
at À788C for monocarbinol compounds, was not observed in
the case of tetraallyl dicarbinol 5b and hexaallyl tricarbinol
6b. Therefore, the reaction time was lengthened to 30 min
for 5b and to 1 hour for 6b.
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General Procedure for the Synthesis of AB3 Arenol
Triallyl Dendrons fromthe Corresponding Methoxy
Derivatives
A mixture of 2c or 3c (45 mmol) and (n-Bu)4NI (54 mmol,
19.9 g) in 30 mL of CH2Cl2, was cooled to À788C. Then, a
solution of 1 M BCl3 in hexane (56 mmol, 56 mL) was
slowly added to the reaction mixture. After 12 h stirring,
49 mL of H2O was added to the mixture followed by
118 mL of 6 N HCl. The product was extracted with Et2O
(30 mL”3) and the organic layer washed with a solution
(20 mL) of Na2S2O3 and dried over Na2SO4. The solvent was
removed under vacuum and the product purified by chroma-
tography on a silica gel column with a petroleum ether/di-
ethyl ether eluent mixture.
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Supporting Information
Full characterization of all new compounds and experimen-
tal procedures are given in the Supporting Information sec-
tion.
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Acknowledgements
Financial Support from the University Bordeaux 1,the
CNRS,the ANR-06-BLAN-0215 and the MRT (LP) is grate-
fully acknowledged.
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