Preparation of novel polythioether dendrons on a solid support

Article abstract of DOI:10.1039/b302324a

A synthetic scheme for the solid-phase synthesis of unprecedented polythioether dendrons has been established, the dendrons prepared up to the fourth generation, and the applicability of the dendronized resins for supported catalysis has been demonstrated

Full text of DOI:10.1039/b302324a

Preparation of novel polythioether dendrons on a solid support†
Adi Dahan, Avi Weissberg and Moshe Portnoy*
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv,
69978, Israel. E-mail: portnoy@post.tau.ac.il; Fax: (+972)3-640-9293; Tel: (+972)3-640-6517
Received (in Cambridge, UK) 27th February 2003, Accepted 1st April 2003
First published as an Advance Article on the web 22nd April 2003
A synthetic scheme for the solid-phase synthesis of unprece-
dented polythioether dendrons has been established, the
dendrons prepared up to the fourth generation, and the
applicability of the dendronized resins for supported cataly-
sis has been demonstrated.
Of the various dendritic systems prepared during the past two
decades,1 many are based on heteroatom-containing functional
groups (i.e. amines, amides, ethers) as connectors between the
monomers. Although sulfur-based functional groups are abun-
dantly represented in organic compounds, the only known
example of a dendritic molecule with sulfur-derived connecting
Fig. 1 Polythioether dendrons on a solid support.
units is that of a poly(m-phenylene sulfide) dendron prepared by
Gingras.2 Molecules combining dendritic architecture and low-
valent sulfur, motifs highly popular in nanochemistry, may be
useful for various applications in this rapidly evolving field.3
While most of the dendritic systems are prepared in solution,
solid-phase synthesis of a number of dendritic molecules has
been reported, mainly over the last five years.4 The number of
types of supported dendrons is limited and includes poly-
phenylacetylenes, polyethers, polyureas and a number of
polyamides (e.g. polylysine, polyamidoamine).5–8 Recently, we
developed a novel synthetic route to the solid phase synthesis of
poly(aryl benzyl)ether dendrons.9 Herein we report the efficient
synthesis of their sulfur analogues, poly(aryl benzyl)thioether
dendrons, Gn(X), on a solid support (Fig. 1).
The relevant monomer 1 is not commercially available and its
synthesis has never been reported. Thus, the synthetic procedure
for the synthesis of 1 (or its synthone) had to be developed.
Luckily, the commercially available 5-hydroxy isophthalate
diester 2 (the monomer that we used for the preparation of the
polyether dendrons) can easily be converted into 3, the
dimethylcarbamoyl derivate of 1, via the Newman–Kwart
Scheme 1 Reagents and conditions: a) DABCO, dimethylthiocarbamoyl
chloride, DMA, 75 °C. b) 280 °C, 10 min.
rearrangement (Scheme 1).10,11 The procedure is high-yielding
and can be performed on a multigram scale. Compound 3 can be
converted to 1 via methanolysis. However, the following
purification is difficult due to the strong propensity of 1 to
undergo oxidation. Fortunately, we discovered that 3 could be
used in the relevant dendron-building procedures, forming 1 in
situ.
The synthetic procedure is based on benzyl halide substitu-
tion by 1, formed in situ, reduction of the esters and
chlorodehydroxylation of the formed alcohols (Scheme 2).
Thus, in three steps, the benzyl halide is reformed as the
terminal function and the next generation of the dendron can be
assembled. The synthesis, performed on Wang Bromo resin,
yielded, in 10 steps, 42% of the fourth generation ester-
terminated dendron. The synthesis was monitored, and the
products characterized, using gel-phase 13C NMR as well as
1
acidolytic cleavage, followed by H and 13C NMR and mass
spectrometry. Surprisingly, the cleavage always occurred
between the resin and the Wang linker and not between the
linker and the dendron (Scheme 3). Thus, a p-hydroxybenzyl-
protected version of the dendron was always released from the
resin. While the linker/protecting group is clearly visible in the
† Electronic supplementary information (ESI) available: procedures for the
preparation of monomer 3, resins G1–G4, 4–8, and relevant character-
isation data. See http://www.rsc.org/suppdata/cc/b3/b302324a/
Scheme 2 Reagents and conditions: a) 3, NaOMe 0.5 M in methanol, DMF, 70 °C. b) LiBH4, B(OMe)3, THF, 67 °C. c) C2Cl6, PPh3, THF, r.t.
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Homogeneous catalysis with Pd complexes of such ligands has
recently been reported.16 Incubation of second- and third-
generation dendritic resins, with Pd(PhCN)2Cl2 in THF at 70
°C, formed deep red resins 6. Although severe broadening of
signals, both in gel-phase 13C NMR of the resins and 1H NMR
of the cleavage solutions, prevented characterization of the
formed complexes, we have been able to characterize 8, the
pincer-type Pd complex of a supported non-dendritic model
SCS ligand 7 (Scheme 6). Preliminary experiments demon-
strated that resins 6 and 8 are efficient and recyclable catalysts
for the Heck reaction of iodobenzene and methyl acrylate (eqn.
1b).17
Scheme 3 Cleavage of the dendrons from the support.
In conclusion, we developed a practical and efficient route to
novel polythioether dendrons on solid support and demon-
strated their potential use for supported catalysis. It is likely
that, due to their unique structure, these compounds will be
applied in other fields of material sciences as well.
We gratefully acknowledge partial support of this work by a
grant from the Ministry of Science, Israel.
Notes and references
Scheme 4 Reagents and conditions: a) N,NA-diisopropylcarbodiimide,
1 (a) G. R. Newkome, C. N. Moorefield and F. Vögtle, Dendritic
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2 A. Van Bierbeek and M. Gingras, Tetrahedron Lett., 1998, 39, 6283.
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G. J. Vansco, F. C. J. M. van Veggel and D. N. Reinhoudt, Adv. Funct.
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DMAP, DMF. b) Pd(dba)2, THF, r.t.
1H and 13C NMR spectra, it is cleaved under the CI-MS
conditions and disulfide-bridged dendron dimers are observed
in the MS spectra.
1
The aforementioned H NMR measurements demonstrated
excellent conversion and purity of each of the three repetitive
steps as the following characteristic changes. Immobilization of
1 is accompanied by complete disappearance of the –CH2Cl
signal (4.51 ppm) and appearance of the lowfield aromatic
signals (8.46 and 8.14 ppm). Reduction results in complete
disappearance of the signals of the isophthalate diester along
with the appearance of –CH2OH/–CH2OCOCF3 peaks (4.81
and 5.35 ppm respectively). The latter are cleanly replaced by
the –CH2Cl signal upon chlorodehydroxylation.
Potential catalytic uses of the novel dendron constructs were
demonstrated.12 Thus, the third-generation OH-terminated
dendron was esterified with 4-(diphenylphosphino)benzoic acid
and the formed phosphine-terminated resin, 4, was complexed
with Pd(0) using a Pd(dba)2 precursor (Scheme 4).13,14 The
polystyrene/polythioether dendron/Pd(0)–phosphine complex
construct, 5, was tested as a catalyst in the Heck reaction of
bromobenzene and methyl acrylate (eqn. 1a). Although low-
valent sulfur-containing molecules, are frequently reported as
catalytic poisons, this was not the case with the thioether
dendron-based catalyst and respectable activity was observed
(89% yield after 14 h at 120 °C with 2.5% Pd).
4 R. J. M. Klein Gebbink, C. A. Kruithof, G. P. M. van Klink and G. van
Koten, Rev. Mol. Biotechnol., 2002, 90, 183.
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(1)
13 A. Dahan and M. Portnoy, Org. Lett., 2003, 5, in press.
Moreover, we discovered that, for iodobenzenes as substrates
in the Heck reaction, there is no need for phosphines on the
dendron. In fact, each isophthalate-derived unit in the interior of
the dendron can serve as a precursor to the pincer complex of
the SCS monoanionic tridentate ligand (Scheme 5).3,15,16
14 Pd coordination to phosphines was confirmed by 31P NMR; Pd loading:
0.47 mmol g21
.
15 (a) M. Albrecht and G. van Koten, Angew. Chem., Int. Ed., 2001, 40,
3750 and references therein (b) H.-J. van Manen, R. H. Fokkens, F. C.
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(c) J. M. Pollino and M. Weck, Synthesis, 2002, 1277.
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17 For instance, with 6a, 2.5% Pd: 1st cycle 100% yield, 2nd cycle 98%
yield.
Scheme 5 Metallation of the dendron units.
Scheme 6 Reagents and conditions: a) 11-bromoundecan-1-ol, BF3·OEt2, DCM, cyclohexane, r.t. b) Dimethyl 5-hydroxyisophthalate, LiH, DMF, 60 °C. (c)
LiBH4, B(OMe)3, THF, 67 °C. d) C2Cl6, PPh3, THF, r.t. e) HSPh, Cs2CO3, DMF, 70 °C. f) Pd(PhCN)2Cl2, THF, 67 °C.
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