Polymer-supported formamides as reusable organocatalysts for allylation of aldehydes with allyltrichlorosilane

Article abstract of DOI:10.1039/b210826g

New types of polymer-supported formamides have been synthesized from chloromethylated resins and formamides; it was found that the polymers worked well as organocatalysts in the allylation of aldehydes with allyltrichlorosilane to afford homoallylic alcoh

Full text of DOI:10.1039/b210826g

Polymer-supported formamides as reusable organocatalysts for allylation
of aldehydes with allyltrichlorosilane
Chikako Ogawa, Masaharu Sugiura and Shu¯ Kobayashi*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033,
Japan. E-mail: skobayas@mol.f.u-tokyo.ac.jp
Received (in Cambridge, UK) 5th November 2002, Accepted 2nd December 2002
First published as an Advance Article on the web 20th December 2002
New types of polymer-supported formamides have been
synthesized from chloromethylated resins and formamides;
it was found that the polymers worked well as organocata-
lysts in the allylation of aldehydes with allyltrichlorosilane to
afford homoallylic alcohols in high yields; the polymers were
easily recovered and reused several times without loss of
activity.
to be more reactive than 2 (entry 1 vs. 2). Next, we examined the
effect of the loading levels of PS-Formamide 1. It was found
that the polymers with higher loadings showed higher activity,
though the difference between 2.12 and 4.66 mmol g21 loadings
was not significant (entries 3–7). Moreover, the yield of the
desired homoallylic alcohol was improved when the amounts of
1 and allyltrichlorosilane were increased (entries 8–10). Finally,
it is noted that even a catalytic amount of 1 was shown to be
effective at a longer reaction time or at a higher concentration
(entries 11 and 12).
Metal-free organocatalysts have been intensively studied from
the viewpoint of their environmentally benign nature.1 Com-
pared with metal-catalyzed reactions, while there is no concern
of contamination, waste and disposal of metals in reactions
using organocatalysts, problems have been incurred in the
separation of the catalysts from the products. Polymer-
supported organocatalysts may address this issue; however,
only a limited number of examples have been reported.2 This is
in remarkable contrast to versatile metal-containing polymer-
supported catalysts reported, in the use of which, however,
leaching of metals from polymer supports is still a serious
problem in many cases.3
The allylation of other aldehydes was tested under the
optimized conditions (Table 2). In all cases, the desired
We have recently reported that aldehydes4 or hydrazones5
react with allyltrichlorosilanes in the presence of a Lewis base
such as N,N-dimethylformamide (DMF) and hexamethylphos-
phoramide (HMPA) without any metal catalysts, to afford the
corresponding homoallylic alcohols or homoallylic hydrazines
in high yields with high diastereoselectivities.6 In these
reactions, the Lewis base acts as an organocatalyst, coordinating
to the silicon atom of allyltrichlorosilanes to form reactive
hypervalent silicates. Although it is easy to remove Lewis bases
such as DMF and HMPA from the products by simple
extraction, immobilization of these Lewis bases onto polymers
would lead to more convenient and efficient reactions and
processes. Herein, we report the first example of polymer-
supported formamides7 as recoverable and reusable organoca-
talysts.
To begin the study of polymer-supported organocatalysts, we
prepared chloromethylated resins with several loadings from a
cross-linked polystyrene and chloromethyl methyl ether in the
presence of a catalytic amount of SnCl4.8 The loading levels of
the resins ranged from 2.22 to 5.11 mmol g21. Commercially
available Merrifield resins (0.63 and 1.20 mmol g21) were also
used. Five resins were then reacted with N-methylformamide
under basic conditions. It was revealed that the formamide
function could not be introduced using K2CO3 as a base in THF,
but that treatment of the chloromethylated resins with NaH in
DMF gave the desired polymer-supported formamide (PS-
Formamide 1) in excellent yields (99% to quantitative). The
precise structure of 1 was confirmed by 13C Swollen Resin
Magic Angle Spinning (SR-MAS) NMR9,10 and IR analyses,
and the loadings of 1 were determined by chlorine titrations.
Polymer-supported N-formylpiperazine (PS-Formamide 2) was
also prepared according to a similar procedure.
Table 1 Optimization of the reaction conditions
Entry Polymer
x
y
z
Conc./M
Yield (%)
1
2
3
4
5
6
7
8
9
1
2
1
1
1
1
1
1
1
1
1
1
100
100
50
50
50
50
50
100
100
200
10
0.61
0.61
0.62
1.10
2.12
3.22
4.66
3.22
3.22
3.22
3.22
3.22
3
3
0.06
0.06
0.33
0.33
0.33
0.33
0.33
0.33
0.33
0.33
0.33
0.66
40
26
43
49
56
58
58
73
91
92
54
79
1.5
1.5
1.5
1.5
1.5
1.5
3
3
3
3
10
11a
12
10
a For 24 h.
Table 2 Allylation of aldehydes using PS-Formamide 1
Entry
R
x (mol%)
Time/h
Yield (%)
1
2
3
4
5
6
PhCH2CH2
Ph
p-Tol
p-NO2Ph
1-Naphtyl
PhCHNCH
100
200
300
300
300
300
9
9
40
12
34
12
91
90
87
95
92
66
We then performed a model reaction of 3-phenylpropanal
with allyltrichlorosilane using PS-Formamides 1 and 2. Acet-
onitrile was chosen as an appropriate solvent, in which no
reaction occurred in a control experiment. Several reaction
conditions were examined, and the results are summarized in
Table 1. In the initial experiments, PS-Formamide 1 was shown
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homoallylic alcohols were obtained in good to excellent yields,
although 300 mol% of PS-Formamide 1 and longer reaction
times were required to complete the reactions in some cases.
One advantage of polymer-supported catalysts is that the
catalysts can be readily recovered and reused, even when excess
amounts of catalysts are used as promoters in the reactions. For
development of truly efficient polymer-supported catalysts, it is
critical that recovery is simple and that the recovered catalysts
retain their activity through multiple trials. We thus investigated
the reusability of PS-Formamide 1. In a preliminary attempt, the
activity of the polymer-supported formamide decreased during
multiple runs. It was observed that the shape of PS-Formamide
1 changed after repeated uses. At this stage, we suspected that
physical destruction of the polymer matrix by magnetic stirring
might occur to induce deactivation of the formamide. Thus, we
used an automatic shaker instead of a magnetic stirrer to
suppress the destruction of the polymer. It was interesting to
find that shaking instead of stirring the reaction mixture was
very effective, and that the activity of the polymer-supported
formamide was retained even with multiple use to afford the
desired homoallylic alcohols in high yields (Table 3). Recovery
of the formamide was quantitative in all three runs, and no
significant loss of activity of the formamide was observed. In
addition, recovered samples of PS-Formamide 1 showed
exactly the same 13C NMR spectra as that of the freshly
prepared 1.
A typical experimental procedure is as follows: an aldehyde
(0.3 mmol), allyltrichlorosilane (0.9 mmol) and PS-Formamide
1 (10–300 mol%) were combined in acetonitrile (1 cm3). The
mixture was stirred or shaken for 9–40 h at room temperature.
For the reuse of 1, shaking was recommended. After the
reaction was complete, the mixture was quenched with water,
and the catalyst 1 was recovered by filtration. A general work-
up and purification by preparative TLC afforded the desired
homoallylic alcohol.
In summary, we have synthesized new types of polymer-
supported formamides as immobilized organocatalysts, which
work well in allylation of aldehydes with allyltrichlorosilane.
Easy and efficient recovery and reusability of the polymer-
supported formamides have been demonstrated, and this may
offset the use of the rather higher loadings of the formamides at
this stage. It is noted that this report is the first example of
successful usage of polymer-supported formamides as Lewis
base-organocatalysts. Further investigations to survey the scope
and limitations of the polymer-supported formamides as well as
to develop other polymer-supported organocatalysts are in
progress.
This work was partially supported by CREST and SORST,
Japan Science Technology Coporation and a Grant-in-Aid for
Scientific Research from Japan Society of the Promotion of
Sciences.
Notes and references
1 For a review on enantioselective organocatalysts, see: P. I. Dalko and L.
Moisan, Angew. Chem., Int. Ed., 2001, 40, 3726.
2 For a recent report on soluble polymer-supported prolines as im-
mobilized organocatalysts, see: M. Benaglia, M. Cimquini, F. Cozzi, A.
Puglisi and G. Celentano, Adv. Synth. Catal., 2002, 344, 533.
3 For a recent review on recoverable catalysts and reagents using
recyclable polystyrene-based supports, see: C. A. McNamara, J. Dixon
and M. Bradley, Chem. Rev., 2002, 102, 3275.
4 S. Kobayashi and K. Nishio, Tetrahedron Lett., 1993, 34, 3453; S.
Kobayashi and K. Nishio, J. Org. Chem., 1994, 59, 6620.
5 S. Kobayashi and R. Hirabayashi, J. Am. Chem. Soc., 1999, 121, 6942;
R. Hirabayashi, C. Ogawa, M. Sugiura and S. Kobayashi, J. Am. Chem.
Soc., 2001, 123, 9493; C. Ogawa, M. Sugiura and S. Kobayashi, J. Org.
Chem., 2002, 67, 5359.
6 For related enantioselective allylations of aldehydes with allyltri-
chlorosilanes, see: S. E. Denmark and J. Fu, J. Am. Chem. Soc., 2001,
123, 9488; S. E. Denmark, D. M. Coe, N. E. Patt and B. D. Griedel, J.
Org. Chem., 1994, 59, 6161; M. Nakajima, M. Saito and S. Hashimoto,
J. Am. Chem. Soc., 1998, 120, 6419; K. Iseki, S. Mizuno, Y. Kuroki and
Y. Kobayashi, Tetrahedron, 1999, 55, 977; T. Shimada, A. Kina, S.
Ikeda and T. Hayashi, Org. Lett., 2002, 124, 2477.
7 Similar types of polymeric formamides as phase transfer catalysts were
reported. S. Kondo, Y. Inagaki and K. Tsuda, J. Polym. Sci. Polym. Lett.
Ed., 1984, 22, 249; S. Kondo, Y. Inagaki, H. Yasui, M. Iwasaki and K.
Tsuda, J. Polym. Sci. Part A: Polym. Chem., 1991, 29, 243; see also: I.
Voigt, F. Simon, K. Esthel, S. Spange and M. Friedrich, Langmuir,
2001, 17, 8355.
8 S. Kobayashi and M. Moriwaki, Tetrahedron Lett., 1997, 38, 4251.
9 S. Kobayashi, R. Akiyama, T. Furuta and M. Moriwaki, Molecules
Online, 1998, 2, 35; S. Kobayashi, Chem. Soc. Rev., 1999, 28, 1; S.
Kobayashi and R. Akiyama, Pure Appl. Chem., 2001, 73, 1103.
10 Polymer-supported formamide 1 was prepared by the following
procedure: N-methylformamide (30 mmol) in DMF (30 cm3) were
added slowly to sodium hydride (30 mmol) in DMF (30 cm3) and then
chloromethylated resin (10 g, 11.0 mmol) was added. The reaction
mixture was stirred for 12 h at room temperature and the reaction then
stopped with water (15 cm3). The polymer was filtered off and washed
three times with methanol (15 cm3), diethyl ether (15 cm3), tetra-
hydrofuran (15 cm3) and dichloromethane (15 cm3) and then dried for
24 h under vacuum. 13C SR-MAS NMR of 1 (100 MHz, CDCl3,
selected): d 162.4 (CNO), 53.1 (CH2), 33.9 (CH3).
Table 3 Reuse of PS-Formamide 1
Run
1st
2nd
3rd
Yielda (%)
Recovery (%)
90 (90)
Quant.
86 (85)
Quant.
86 (43)
Quant.
a Yields obtained using a magetic stirrer are given in parentheses.
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