Rasta resin-PPh3BnCl and its use in chromatography-free carbonyl cyanosilylation reactions

Article abstract of DOI:10.1055/s-0030-1259515

Rasta resin-PPhnCl, a new heterogeneous polystyrene-based phosphonium salt, has been synthesized and used to catalyze cyanosilylation reactions of aldehydes and ketones. It was found to be more efficient as a catalyst than a similar heterogeneous phosphon

Full text of DOI:10.1055/s-0030-1259515

LETTER
551
Rasta Resin-PPh3BnCl and its Use in Chromatography-Free Carbonyl
Cyanosilylation Reactions
Rasta
R
esin-PPh
B
3 anCl n Teng, Patrick H. Toy*
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China
Fax +85228571586; E-mail: phtoy@hku.hk
Received 29 October 2010
been a report of a polymer-supported phosphonium salt
catalyzing both the conversion of alcohols to the corre-
sponding THP, THF, and EE acetals, and the hydrolysis of
such protected alcohols.4
Abstract: Rasta resin-PPh3BnCl, a new heterogeneous polysty-
rene-based phosphonium salt, has been synthesized and used to cat-
alyze cyanosilylation reactions of aldehydes and ketones. It was
found to be more efficient as a catalyst than a similar heterogeneous
phosphonium salt anchored onto a polystyrene-based on the Merri-
field resin architecture of 2% divinylbenzene cross-linking. In these
reactions rasta resin-PPh3BnCl was separated from the desired reac-
tion product simply by filtration, and it could be reused without sig-
nificant loss of catalytic activity numerous times.
We have been examining the use of various organic poly-
mers as supports for organic chemistry,5 especially in the
context of polymer-supported phosphine reagents and cat-
alysts,6–8 and have recently reported the use of JandaJel9
as a core for the rasta resin architecture (Figure 1)10 in the
synthesis of rasta resin-PPh3 (1, Scheme 2).11 This reagent
was found to be superior in Wittig reactions to other poly-
mer-supported phosphine reagents anchored onto the
more common Merrifield resin architecture of divinylben-
zene cross-linked polystyrene, and we attributed this ob-
servation to the fact that the phosphine groups of 1 were
located on the flexible polystyrene grafts rather than on
the rigid, heterogeneous core. Thus, the phosphine groups
of 1 were readily accessible to the reacting substrates even
when the polymer swelled poorly in the reaction solvent.
For example, some of the one-pot Wittig reactions we re-
ported were performed in 1-PrOH, a solvent that does not
swell cross-linked polystyrene. As a follow up to this
work, we wanted to see if 1 would also represent an im-
proved platform for phosphonium salt organocatalysis
compared to polymers related to Merrifield resin. Herein
we report the reaction of 1 with benzyl chloride to form 2
(Scheme 2), and its use as a catalyst in carbonyl group
cyanosilylation reactions.
Key words: polymer-supported catalyst, polystyrene, phosphoni-
um salt, organocatalysis, cyanosilylation
The use of phosphonium salts to catalyze reactions is an
emerging aspect of organocatalysis.1 For example, they
have recently been reported to efficiently convert various
aldehydes2 and ketones3 into the corresponding silylated
cyanohydrins in the presence of trimethylsilyl cyanide un-
der mild reaction conditions (Scheme 1). There has also
O
Ph3P+MeI– (10 mol%)
CH2Cl2
TMSO
R1
CN
H
TMSCN
+
R1
H
O
TMSO
R1
CN
R2
Ph3P+BnCl– (1–5 mol%)
CHCl3
TMSCN
+
R1
R2
Scheme 1 Cyanosilylation of aldehydes and ketones catalyzed by
phosphonium salts
+
PPh2BnCl–
PPh2
BnCl, CHCl3
60 °C
JJ
6n
JJ
n O
N
n O
N
6n
JJ
= JandaJel
2 (RR-PPh3BnCl)
(0.92 mmol/g)
1 (RR-PPh3)
BnCl, CHCl3
60 °C
+
PPh3BnCl–
PS
PPh3
PS
PL-PPh3
3 (PL-PPh3BnCl)
(1.17 mmol/g)
Scheme 2 Synthesis of 2 and 3
SYNLETT 2011, No. 4, pp 0551–0554
x
x.
x
x.
2
0
1
1
Advanced online publication: 27.01.2011
DOI: 10.1055/s-0030-1259515; Art ID: W17310ST
© Georg Thieme Verlag Stuttgart · New York

552
Y. Teng, P. H. Toy
LETTER
As outlined in Scheme 2, 1 (RR-PPh3)11 was reacted with
benzyl chloride in hot CHCl3 to afford 2 (RR-
PPh3BnCl).12 Analysis of 2 by 31P NMR spectroscopy in-
dicated complete conversion of the phosphine groups of 1
to the corresponding phosphonium salts. Elemental anal-
ysis was used to determine the loading level of 2 to be 0.92
mmol PPh3BnCl/g. For the sake of comparison, a com-
mercially available polystyrene-supported phosphine re-
agent based on the Merrifield resin architecture (PL-PPh3
from Polymer Laboratories) was also converted to the cor-
responding phosphonium salt 3 (PL-PPh3BnCl) using a
similar procedure. The loading level of 3 was determined
by elemental analysis to be 1.17 mmol PPh3BnCl/g and its
31P NMR spectrum was similar to that of 2.
R
living radical polymerization
initiation groups
heterogeneous
core
nO
N
flexible functionalized
grafts
rasta resin
Figure 1 The rasta resin concept
Table 1 Cyanosilylation of Aldehydes Using 2 or 3
O
TMSO
R
CN
H
We next set out to compare the performance of 2 and 3 as
catalysts in the cyanosilylation of various aldehydes using
TMSCN. It should be noted that in the original report of
using PPh3BnCl to catalyze such reactions by Wang and
Tian, only ketones were studied as starting materials.3
However, Córdoba and Plumet had previously described
the use of PPh3MeI as the catalyst in cyanosilylation reac-
tions of aldehyde substrates. The reactions with 2 were
performed on a 0.5 mmol scale at 50 °C in CHCl3 until
TLC analysis indicated the complete disappearance of
starting material. As can be seen in Table 1, all of the eight
aldehydes studied (4a–h) afforded nearly quantitative
yield of the desired product (5a–h) in 2.5 hours or less.13
In these reactions, the product was obtained simply after
filtration of the reaction mixture to remove 2 and concen-
tration to remove the excess TMSCN and the solvent. All
2 or 3
TMSCN
+
R
H
4a–h
5a–h
Entry Substrate Product
Time (h) Yield (%)a
NC
OTMS
1
4a
0.5
97
H
5a
NC OTMS
H
1
99
2
3
4
4b
4c
4d
(4)b
(96)b
Ph
5b
NC OTMS
H
1
99
Ph
5c
NC OTMS
1
0.5
99
products 5a–h were essentially pure according to H
(2)b
(94)b
Ph
H
NMR spectroscopy. We next used 3 as the catalyst with
two randomly chosen aldehydes, 4b and 4d (Table 1, en-
tries 2 and 4). While 3 also afforded high yield in these re-
actions, they took much longer to proceed to completion
than did the reactions using 2 as the catalyst.
5d
NC OTMS
Cl
H
5
6
7
4e
4f
0.5
0.5
2.5
99
99
99
When ketones 6a–h were used in cyanosilylation reac-
tions with TMSCN and 2 as the catalyst on a 0.5 mmol
scale, the desired products 7a–h were obtained in excel-
lent yields in reactions that were somewhat slower than
the reactions with aldehydes (Table 2). In these reactions
of ketones, 1.5–12 hours were required for complete con-
sumption of the starting material. Nevertheless, 2 was a
more efficient catalyst than 3 when they were compared
side by side with the substrates 6b and 6h (Table 2, entries
2 and 8). Just as before, essentially pure products 7a–h
were isolated from the reactions after only filtration and
concentration. It should be noted that our results using 2
as catalyst are comparable to what Wang and Tian report-
ed.3 When they used PPh3BnCl as the catalyst, they ob-
tained 86–99% isolated yield of the desired product from
18 different ketone starting materials, using 0.01 or 0.05
equivalents of catalyst, 1.2 or 1.5 equivalents of TMSCN,
at 25 °C or 50 °C, after 4–48 hours in CHCl3.
5e
NC OTMS
H
Br
5f
NC OTMS
H
4g
MeO
5g
NC
OTMS
H
8
4h
0.5
99
5h
a Isolated yield of reactions using 0.5 mmol 4a–h, 0.75 mmol
TMSCN, and 0.025 mmol 2 in 0.3 mL CHCl3 stirring at 50 °C.
b Result using 3 as the catalyst.
Lastly, the recyclability of 2 was examined in the conver-
sion of 6h to 7h. For these reactions, in order to further es-
tablish the practical nature of 2, we increased the scale
Synlett 2011, No. 4, 551–554 © Thieme Stuttgart · New York

LETTER
Rasta Resin-PPh3BnCl
553
Table 2 Cyanosilylation of Ketones Using 2 or 3
Table 3 Recycling of 2
O
O
TMSO
CN
TMSO
R1
CN
R2
2 or 3
TMSCN
+
R1
R2
TMSCN
2
+
6a–h
7a–h
O2N
O2N
Entry
1
Substrate Product
Time (h) Yield (%)a
6h
7h
Catalyst recovery (%) Yield (%)a
NC
OTMS
Run
1
Time
1.5
1.5
1.5
1.5
2.5
3
6a
6b
4.5
81
99
92
96
91
97
99
99
99
98
93
99
99
99
99
98
99
7a
NC
2
OTMS
3
1.5
94
2
(4)b
(94)b
4
7b
5
NC OTMS
6
3
4
6c
12
10
99
98
Ph
7
3
7c
NC OTMS
8
3
6d
Ph
a Isolated yield of reactions using 3 mmol 6h, 4.5 mmol TMSCN, and
0.15 mmol 2 in 1.8 mL CHCl3 stirring at 50 °C.
7d
NC OTMS
5
6
6e
6f
11
10
95
99
terial. Direct comparison of 2 and a Merrifield resin based
analogue 3 indicated that the rasta-resin architecture al-
lowed 2 to be more efficient as a catalyst. It is believed
that this is due to the positioning of the catalytic phospo-
nium groups of 2 on flexible grafts that are more accessi-
ble to reagents and substrates than are the catalytic groups
of 3, which are located in the interior of the heterogeneous
beads. Additional studies to further demonstrate the utility
of the rasta-resin architecture are currently under way, and
the results of these will be reported in due course.
7e
7f
NC OTMS
Cl
NC OTMS
7
8
6g
6h
10
99
Br
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
7g
NC OTMS
1.5
99
(4)b
(93)b
Acknowledgment
O2N
This research was supported financially by the University of Hong
Kong and the Research Grants Council of the Hong Kong S. A. R,
P. R. of China (Project No. HKU 704108P). We thank Polymer
Laboratories (Paul Boguszewski) for gifts of materials.
7h
a Isolated yield of reactions using 0.5 mmol 6a–h, 0.75 mmol
TMSCN, and 0.025 mmol 2 in 0.3 mL CHCl3 stirring at 50 °C.
b Result using 3 as the catalyst.
References and Notes
from 0.5 mmol of ketone to 3.0 mmol. As can be seen in
Table 3, 2 was efficiently recovered and readily reusable.
We were able to use it in eight reaction cycles with no de-
crease in product yield, and only a slight decrease in reac-
tion efficiency. It should be noted that 31P NMR analysis
of 2 recovered after the 8th reaction cycle afforded a spec-
trum that was essentially identical to that for freshly pre-
pared 2.12
(1) Werner, T. Adv. Synth. Catal. 2009, 351, 1469.
(2) Córdoba, R.; Plumet, J. Tetrahedron Lett. 2003, 44, 6157.
(3) Wang, X.; Tian, S.-K. Tetrahedron Lett. 2007, 48, 6010.
(4) Hon, Y.-S.; Lee, C.-F.; Chen, R.-J.; Szu, P.-H. Tetrahedron
2001, 57, 5991.
(5) Lu, J.; Toy, P. H. Chem. Rev. 2009, 109, 815.
(6) For a review of polymer-supported phosphines, see: Guino,
M.; Hii, K. K. Chem. Soc. Rev. 2007, 36, 608.
(7) For our work regarding cross-linked polymers, see:
(a) Kwok, M.; Choi, W.; He, H. S.; Toy, P. H. J. Org. Chem.
2003, 68, 9831. (b) Zhao, L. J.; He, H. S.; Shi, M.; Toy,
P. H. J. Comb. Chem. 2004, 6, 680. (c) Zhao, L.-J.; Kwong,
C. K.-W.; Shi, M.; Toy, P. H. Tetrahedron 2005, 61, 12026.
In conclusion, we have applied the rasta-resin architecture
as a support for a recyclable phosphonium salt catalyst 2,
and used this material to catalyze the cyanosilylation of
various aldehydes and ketones with TMSCN in reactions
that ranged in scale from 0.5 to 3.0 mmol of starting ma-
Synlett 2011, No. 4, 551–554 © Thieme Stuttgart · New York

554
Y. Teng, P. H. Toy
LETTER
Haddleton, D. M.; Fontaine, L. J. Comb. Chem. 2006, 8,
522. (f) Fournier, D.; Pascual, S.; Montembault, V.;
Fontaine, L. J. Polym. Sci., Part A: Polym. Chem. 2006, 44,
5316. (g) Pawluczyk, J. M.; McClain, R. T.; Denicola, C.;
Mulhearn, J. J.; Rudd, D. J.; Lindsley, C. W. Tetrahedron
Lett. 2007, 48, 1497. (h) Chen, G.; Tao, L.; Mantovani, G.;
Geng, J.; Nystroem, D.; Haddleton, D. M. Macromolecules
2007, 40, 7513.
(8) For our work regarding noncross-linked polymers, see:
(a) Harned, A. M.; He, H. S.; Toy, P. H.; Flynn, D. L.;
Hanson, P. R. J. Am. Chem. Soc. 2005, 127, 52. (b) He,
H. S.; Yan, J. J.; Shen, R.; Zhuo, S.; Toy, P. H. Synlett 2006,
563. (c) Kwong, C. K.-W.; Huang, R.; Zhang, M.; Shi, M.;
Toy, P. H. Chem. Eur. J. 2007, 13, 2369. (d) Kwong, C.
K.-W.; Fu, M. Y.; Law, H. C.-H.; Toy, P. H. Synlett 2010,
2617.
(9) (a) Toy, P. H.; Janda, K. D. Tetrahedron Lett. 1999, 40,
6329. (b) Toy, P. H.; Reger, T. S.; Janda, K. D. Aldrichimica
Acta 2000, 33, 87. (c) Toy, P. H.; Reger, T. S.; Garibay, P.;
Garno, J. C.; Malikayil, J. A.; Liu, G.-Y.; Janda, K. D.
J. Comb. Chem. 2001, 3, 117. (d) Choi, M. K. W.; Toy, P.
H. Tetrahedron 2004, 60, 2903.
(10) (a) Hodges, J. C.; Harikrishnan, L. S.; Ault-Justus, S. J.
Comb. Chem. 2000, 2, 80. (b) Lindsley, C. W.; Hodges,
J. C.; Filzen, G. F.; Watson, B. M.; Geyer, A. G. J. Comb.
Chem. 2000, 2, 550. (c) McAlpine, S. R.; Lindsley, C. W.;
Hodges, J. C.; Leonard, D. M.; Filzen, G. F. J. Comb. Chem.
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K. A.; Zhao, Z.; Lindsley, C. W. Tetrahedron Lett. 2003, 44,
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(12) See Supporting Information for details.
(13) General Procedure for Cyanosilylation Reactions
To a solution of the aldehyde or ketone substrate (0.5 mmol)
and TMSCN (0.75 mmol) in CHCl3 was added 2 or 3 (0.025
mmol). The reaction mixture was stirred at 50 °C until TLC
analysis indicated that the starting material was completely
consumed. The reaction mixture was then filtered and the
polymer-supported catalyst was washed with CH2Cl2
(2 × 50 mL). The combined filtrate was concentrated in
vacuo to afford the desired product. All products were
characterized by MS, 1H NMR, and 13C NMR spectroscopy.
Synlett 2011, No. 4, 551–554 © Thieme Stuttgart · New York

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