The use of polyhedral oligomeric silsesquioxane (POSS) as a soluble support for organic synthesis: A case study with a POSS-bound isocyanate scavenger reagent

Article abstract of DOI:10.1016/j.tetlet.2010.07.015

The use of polyhedral oligomeric silsesquioxane (POSS) as a soluble support in organic synthesis is reported. A POSS-bound isocyanate was readily synthesised in one step from commercially available starting materials and was isolated in high yield and purity by simple filtration. It was found to perform well as a scavenger for excess amine in the solution phase synthesis of amides and sulfonamides, allowing product isolation in high yield and purity.

Full text of DOI:10.1016/j.tetlet.2010.07.015

Tetrahedron Letters 51 (2010) 4677–4680
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Tetrahedron Letters
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The use of polyhedral oligomeric silsesquioxane (POSS) as a soluble support
for organic synthesis: A case study with a POSS-bound isocyanate scavenger
reagent
*
Mark York , Richard A. Evans
CSIRO Molecular and Health Technologies, Bag 10, Clayton South, Victoria 3169, Australia
CSIRO Future Manufacturing Flagship, Bag 10, Clayton South, Victoria 3169, Australia
Cooperative Research Centre for Polymers, 8 Redwood Drive, Notting Hill, Victoria 3168, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
The use of polyhedral oligomeric silsesquioxane (POSS) as a soluble support for use in organic synthesis is
reported. A POSS-bound isocyanate was readily synthesised in one step from commercially available
starting materials and isolated in high yield and purity by simple filtration. It was found to perform well
as a scavenger for excess amine in the solution phase synthesis of amides and sulfonamides, allowing
product isolation in high yield and purity.
Received 28 April 2010
Revised 21 June 2010
Accepted 2 July 2010
Available online 7 July 2010
Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
Keywords:
POSS
Scavenger
Soluble support
The use of polymer-supported scavenger reagents is an area of
great importance in organic synthesis, allowing the rapid removal
of excess reagents from solution by a simple filtration without re-
course to time-consuming purification protocols.1 Such methodol-
ogy, however, is not without its drawbacks and the use of insoluble
polymer supports leads inevitably to heterogeneous reactions with
slower reaction rates than their solution phase counterparts, to the
need for large excesses of the reagent due to non-uniform accessi-
bility of reactive sites and to the limitations on solvent choice due
to polymer incompatibility. Various approaches have been at-
tempted to overcome these limitations including the use of soluble
polymeric supports2 and chemical tagging with groups allowing
extraction into specific solvents.3 More recently the use of a tetra-
arylphosphonium salt as a solubility control group allowing the
isolation of reagents by the addition of non-polar solvents was
reported.4
During the course of our work using functionalised POSS mate-
rials we observed an interesting trend in solubility, that is, good
solubility in many commonly used organic solvents such as dichlo-
romethane, tetrahydrofuran, chloroform and petroleum ether.
Conversely, in polar solvents such as acetonitrile, methanol, water
and dimethyl sulfoxide the material was insoluble. Herein, we re-
port our results in exploiting this differential solubility to use POSS
as a soluble support for an isocyanate scavenger reagent. The POSS
isocyanate 2 was synthesised in one step by the reaction between
commercially available aminopropylisobutyl POSS, 1 and triphos-
gene (Scheme 1). This gave a near quantitative yield of 2 which
was isolated as a free-flowing colourless solid by the evaporation
of the reaction mixture and washing the residue with acetoni-
trile.12 In addition to the use of 2 as a scavenger reagent, it may
also be of interest to materials chemists working with POSS, as
the isocyanate group offers a convenient handle for conjugation
Polyhedral oligomeric silsesquioxanes (POSS) feature a caged
octacyclic inorganic silicon and oxygen framework surrounded
on the exterior of the cage with eight organic substituents
(Fig. 1).5 POSS-containing materials have found use in a wide range
of potential applications including medical devices,6 OLEDS,7 elec-
tronics8 and packaging.9 Additionally, POSS has been used as a sup-
port for metal catalysts,10 allowing catalyst recovery through a
nanofiltration process.11
* Corresponding author.
E-mail address: mark.york@csiro.au (M. York).
Figure 1.
0040-4039/$ - see front matter Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.015

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M. York, R. A. Evans / Tetrahedron Letters 51 (2010) 4677–4680
Scheme 1.
ing could be further increased by the synthesis of POSS cores bear-
Table 1
ing more than one isocyanate moiety. Additionally 2 was found to
be readily soluble in a number of organic solvents with a solubility
of over 1 g per mL achievable in CH2Cl2. In order to determine the
suitability of compound 2 for use as a scavenger reagent its ability
to scavenge a variety of amines from solution was determined in
comparison with a commercially available polystyrene-(PS)bound
scavenger (Table 1).14
Compound 2 performed well with the complete scavenging of a
variety of 1° and 2° amines (Table 1, entries 1–6 and 10–12). Unsur-
prisingly, the scavenging of N-methylaniline did not proceed to
completion without extended reaction times (Table 1, entries 13–
15). In common with the commercially available PS-bound scaven-
ger, compound 2 was insensitive to atmospheric moisture with per-
formance unchanged after 14 days of atmospheric exposure
(Table 1, entry 7). Scavenging also proceeded in solvents where 2
was largely insoluble such as acetone (Table 1, entry 8), and in sol-
vents where the commercial polymer-bound isocyanate reagent
functioned poorly due to lack of polymer swelling, such as petro-
leum ether (Table 1, entry 9). In order to further evaluate the use
of 2 it was used to scavenge excess 1° and 2° amines in the synthesis
of a small array of amides and sulfonamides (Scheme 2) and the
purity of the final products was evaluated (Table 2).
Formation of the products, 3 was achieved using 1 equivalent of
electrophile and 1.5 equivalents of nucleophilic amine in the pres-
ence of an excess of K2CO3 as base. Subsequent scavenging of resid-
ual amine by 2 (1 equivalent) and its removal from the reaction
mixture by precipitation with CH3CN and filtration gave the prod-
ucts in very good to excellent yields and with high purities (Table 2,
entries 1a and 2–9). If desired, more than 90% of the mixture of
unused 2 and quenched scavenger 4 could be recovered from the
filter cake in high purity by extraction with CH2Cl2. This allows
Entry
Amine scavenged (%)a
POSS isocyanate 2 PS isocyanate
Amine
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
tert-Butylamine
Benzylamine
Phenethylamine
Dipropylamine
Diisopropylamine
Diallylamine
>95
>95
>95
>95
>95
>95
>95
>95
>95
>95
>95
>95
>95
>95
>95
95
95
95
55
>95
>95
>95
42
Diallylamineb
Diallylaminec
Diallylamined
Piperidine
1,2,3,4-Tetrahydroisoquinoline >95
Morpholine
>95
14
N-Methylaniline
N-Methylanilinee
N-Methylanilinef
57
92
>95
>95
a
Reaction performed with 0.214 mmol of isocyanate and 0.107 mmol of amine in
CDCl3 (1 mL) at 22 °C for 1 h. Extent of scavenging determined by 1H NMR spec-
troscopy using MeNO2 as an internal standard.
b
Scavenger exposed to atmosphere for 14 days prior to reaction.
Reaction performed in acetone-d6.
Reaction performed in petroleum ether.
Reaction performed for 5 h.
c
d
e
f
Reaction performed for 18 h.
to nucleophilic groups. The synthesis of an octafunctional POSS iso-
cyanate for the preparation of inorganic–organic hybrid materials
via a hydrosilylation process has been reported previously.13
POSS isocyanate 2 gave a loading of 1.11 mmol of isocyanate per
gram of material, a similar loading level to many commercially
available polymer-bound reagents. It was envisaged that this load-
Scheme 2.

M. York, R. A. Evans / Tetrahedron Letters 51 (2010) 4677–4680
4679
Table 2
Entry
Amine
Electrophile
Product
Yielda (%)
Purityb (%)
1a
90
>95
>95
70
1bc
2
3
4
91
88
92
>95
>95
>95
5
6
92
91
>95
>95
7
8
90
98
85
>95
94
9
>95
a
A mixture of amine (0.31 mmol) and K2CO3 (2.07 mmol) in CH2Cl2 (1 mL) was treated with electrophile (0.21 mmol) and stirred for 1 h. POSS isocyanate 2 (0.21 mmol)
was then added and stirring continued for 1 h. The mixture was then reduced to low bulk under a stream of compressed air, diluted with CH3CN and filtered. The filtrate was
evaporated in vacuo and extracted with CH3CN, evaporation of which gave the desired products.
b
Purity determined by GC and confirmed by 1H NMR spectroscopy.
Reaction performed without scavenger.
c
the possibility of reuse and recycling of the scavenger reagent.
When the reaction was performed in the absence of the scavenger
a product of only 70% purity was obtained (Table 2, entry 1b).
In summary, in order to test the suitability of POSS as a soluble
support for use in organic synthesis we have developed a POSS-
bound isocyanate scavenger reagent, 2. This material was isolated
in one synthetic step in near quantitative yield, it exhibited similar
reactivity to a commercially available polymer-bound scavenger
and has been used to scavenge excess nucleophilic amine in the
synthesis of an array of amides and sulfonamides. Removal of the
scavenger by filtration resulted in the isolation of products in very
good to excellent yields and with high purity.
References and notes
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138, 363–379; (b) Solinas, A.; Taddei, M. Synthesis 2007, 2409–2453; (c) Ley, S.
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Acknowledgements
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The authors thank the Co-operative Research Centre for Poly-
mers and CSIRO Molecular and Health Technologies for their
support.
11. Muller, C.; Nijkamp, M. G.; Vogt, C. Eur. J. Inorg. Chem. 2005, 4011–4021.
12. Experimental procedure: A solution of aminopropylisobutyl POSS, 1 (10.0 g,
11.43 mmol) and N,N-diisopropylethylamine (3.98 mL, 22.87 mmol) in CH2Cl2
(150 mL) was treated portionwise with triphosgene (1.70 g, 5.72 mmol) and
stirred at 22 °C for 2 h. The mixture was then evaporated in vacuo and the
residue washed with CH3CN (3 Â 100 mL) and filtered. Drying at the funnel
gave POSS isocyanate 2, as a colourless, free-flowing solid (10.25 g, 100%). Mp
264–265 °C; 1H NMR (CDCl3, 200 MHz) d 3.28 (t, J = 6.8 Hz, 2H), 1.96–1.70 (m,
Supplementary data
Supplementary data (experimental procedures and data for all
new compounds) associated with this article can be found, in the
online version, at doi:10.1016/j.tetlet.2010.07.015.

4680
M. York, R. A. Evans / Tetrahedron Letters 51 (2010) 4677–4680
9H), 0.96 (dd, J = 0.8 and 6.6 Hz, 42H), 0.71–0.51 (m, 16H); 13C NMR (CDCl3,
50 MHz) 122.0, 45.2, 25.7, 25.1, 23.9, 22.5, 9.2; HRMS (EI) calcd for
32H69NO13Si8 [M+]: 899.2918, found: 899.2895.
13. Neumann, D.; Fisher, M.; Tran, L.; Matisons, J. G. J. Am. Chem. Soc. 2002, 124,
d
13998–13999.
C
14. Sigma–Aldrich 473685. Isocyanate polymer bound, 2% DVB, 200–400 mesh.