A Microencapsulated Lewis Aacid. A New Type of Polymer-Supported Lewis Acid Catalyst of Wide Utility in Organic Synthesis

Full text of DOI:10.1021/ja9739289

J. Am. Chem. Soc. 1998, 120, 2985-2986
2985
the Lewis acids.9 Scandium trifluoromethanesulfonate (scandium
A Microencapsulated Lewis Acid. A New Type of
Polymer-Supported Lewis Acid Catalyst of Wide
Utility in Organic Synthesis
10
triflate, Sc(OTf)
mobilized. Sc(OTf)
we have discovered,11 and many useful synthetic reactions using
3
)
was chosen as the Lewis acid to be im-
3
is a new type of water-stable Lewis acid
12
Sc(OTf)
capsulated Sc(OTf)
Polystyrene (1.000 g) was dissolved in cyclohexane (20 mL) at
0 °C, and to this solution was added powdered Sc(OTf) (0.200
3
have been developed. Preparation of the microen-
Sh uj Kobayashi* and Satoshi Nagayama
3
(MC Sc(OTf) ) was performed as follows:
3
Department of Applied Chemistry, Faculty of Science
Science UniVersity of Tokyo (SUT)
CREST, Japan Science and
4
3
g) as a solid core. The mixture was stirred for 1 h at this
temperature and then slowly cooled to 0 °C. Coacervates were
found to envelop the solid core dispersed in the medium, and
hexane (30 mL) was added to harden the capsule walls. The
mixture was stirred at room temperature for 1 h, and the capsules
Technology Corporation (JST)
Kagurazaka, Shinjuku-ku, Tokyo 162, Japan
ReceiVed NoVember 17, 1997
13,14
were washed with acetonitrile several times and dried at 50 °C.
A scanning electron microscopy (SEM) micrograph and
The utility of polymer catalysts is now well-recognized because
of their ease of workup and of separation of products and catalysts,
from the economical point of view, and in application to industrial
scandium energy-dispersive X-ray (EDX) map of MC Sc(OTf)
prepared are shown in Figure 1. It was found that small capsules
of MC Sc(OTf) adhered to each other, probably due to the small
3
processes, etc.1
,2
In general, catalysts are immobilized on
3
size of the core. Judging from the scandium mapping, Sc(OTf)
was located all over the polymer surface. A possible role for the
benzene rings of the polystyrene in immobilizing Sc(OTf) was
suggested by control experiments using polybutadiene or poly-
ethylene instead of polystyrene. While 43% of Sc(OTf) (100%
3
polymers via coordinate or covalent bonds. While the stability
of polymer catalysts having coordinate bonds is often low,
preparation of polymer catalysts having covalent bonds can be
troublesome and their activities are generally lower than those
of the monomer catalysts.2 On the other hand, Lewis acid-
catalyzed reactions are of great current interest because of the
unique reactivities and selectivities that can be achieved as well
3
3
)
the amount of Sc(OTf)
bound using polybutadiene, no Sc(OTf)
microcapsules prepared using polyethylene. These results may
3
immobilized by polystyrene) was
3
was observed in the
3
as for the mild conditions used. Although many of them have
3
indicate that there is an interaction between Sc(OTf) and the
been applied in industry, there are few examples of polymer-
3
benzene rings of polystyrene.15
supported Lewis acids.4 Recently, we have developed polymer-
5
supported scandium Lewis acids based on Nafion and a
3
We then used MC Sc(OTf) in several fundamental and
6
polyacryronitrile derivative; however, their reactivity was lower
important Lewis acid-catalyzed carbon-carbon bond-forming
than for the monomeric Lewis acids. We now report here an
unprecedented polymer-supported Lewis acid, a microencapsu-
lated Lewis acid, which is readily prepared, has higher activity
than the monomeric Lewis acid, is recoverable and reusable, and
can be applied to many synthetic reactions.
Microcapsules have been used for coating and isolating
substances until such time as their activity is needed, and their
application to medicine and pharmacy has been extensively
studied.7 Recently, much progress has been made in this field;
for example, the size of microcapsule achievable has been reduced
from a few micrometers to nanometers.7,8 Our idea is to apply
this microencapsulation technique to the immobilization of Lewis
acid catalysts onto polymers. That is, Lewis acids would be
physically enveloped by polymer thin films and perhaps stabilized
by the interaction between π electrons of benzene rings of the
polystyrene used as a polymer backbone and vacant orbitals of
reactions. All reactions were carried out on a 0.5 mmol scale in
acetonitrile1 using MC Sc(OTf)
6,17
containing ca. 0.120 g of Sc-
3
(OTf)
normal vessels) and flow systems (using circulating columns). It
was found that MC Sc(OTf) effectively activated aldimines.
3
. The reactions were carried out in both batch (using
3
12b
12b,c,17
12d,17
Imino aldol (Scheme 1), aza Diels-Alder,
cyanation,
and allylation1
2e,17
reactions of aldimines proceeded smoothly
3
to afford respectively the synthetically useful
using MC Sc(OTf)
â-amino ester, tetrahydroquinoline, R-aminonitrile, and homoal-
lylic amine derivatives in high yields. Although it is well-known
that most Lewis acids are trapped and sometimes decomposed
3
by basic aldimines, MC Sc(OTf) worked well in all cases. One
(
9) (a) Greoffrey, F.; Cloke, N. In ComprehensiVe Organometallic Chem-
istry II; Lappert, M. F., Ed.; Pergamon: Oxford, 1995; Vol. 4, p 1. (b)
Edelmann, F. T. In ComprehensiVe Organometallic Chemistry II; Lappert,
M. F., Ed.; Pergamon: Oxford, 1995; Vol. 4, p 11.
(10) Thom, K. F. US Pat. 3615169, 1971; Chem. Abstr. 1972, 76, 5436a.
(
1) For leading references on polymer catalysts, see: Bailey, D. C.; Langer,
S. H. Chem. ReV. 1981, 81, 109. Akelah, A.; Sherrington, D. C. Chem. ReV.
981, 81, 557. Frechet, J. M. J. Tetrahedron 1981, 37, 663.
2) Macromolecule-Metal Complexes; Ciardelli, F., Tsuchida, E., W o¨ hrle,
D., Eds.; Springer: Heidelberg, 1996.
(11) Kobayashi, S.; Hachiya, I.; Araki, M.; Ishitani, H. Tetrahedron Lett.
1993, 34, 3755.
1
(12) (a) Kobayashi, S. Synlett 1994, 689. (b) Kobayashi, S.; Araki, M.;
Ishitani, H.; Nagayama, S.; Hachiya, I. Synlett 1995, 233. (c) Kobayashi, S.;
Ishitani, H.; Nagayama, S. Synthesis 1995, 1195. (d) Kobayashi, S.; Ishitani,
H.; Ueno, M. Synlett 1997, 115. (e) Kobayashi, S.; Nagayama, S. J. Am. Chem.
Soc. 1997, 119, 10049. (f) Kobayashi, S.; Araki, M.; Yasuda, M. Tetrahedron
Lett. 1995, 36, 5773. (g) Kobayashi, S.; Ishitani, H.; Nagayama, S. Chem.
Lett. 1995, 423. (h) Kobayashi, S.; Hachiya, I.; Ishitani, H.; Araki, M. Synlett
1993, 472. (i) Hachiya, I.; Kobayashi, S. J. Org. Chem. 1993, 58, 6958. (j)
Kawada, A.; Mitamura, S.; Kobayashi, S. Synlett 1994, 545.
(
(
3) SelectiVities in Lewis Acid Promoted Reactions; Schinzer, D., Ed.;
Kluwer Academic Publisheres: Dordrecht, The Netherlands, 1989. Santelli,
M.; Pons, J.-M. Lewis Acids and SelectiVity in Organic Synthesis; CRC Press:
Boca Raton, FL, 1995.
(
3
4) Immobilization of AlCl onto polymers or inorganic support materials
has been reported, but the successful applications have been limited. Neckers,
D. C.; Kooistra, D. A.; Green, G. W. J. Am. Chem. Soc. 1972, 94, 9284.
Krzywicki, A.; Marczewski, M. J. Chem. Soc., Faraday Trans. 1 1980, 1311.
Drago, R. S.; Getty, E. E. J. Am. Chem. Soc. 1988, 110, 3311. Clark, J. H.;
Martin, K.; Teasdale, A. J.; Barlow, S. J. J. Chem. Soc., Chem. Commun.
(13) Judging from the recovered Sc(OTf)
3 3
(0.080 g), 0.120 g of Sc(OTf)
was microencapsulated according to this procedure. The weight of the capsules
3
was 1.167 g which contained acetonitrile. MC Sc(OTf) thus prepared can be
stored at room temperature for more than a few months.
1
995, 2037. For montmorillonite-supported zinc chloride, see: Clark, J. H.;
Cullen, S. R.; Barlow, S. J.; Bastock, T. W. J. Chem. Soc., Perkin Trans. 2
994, 1117. For immobilized trityl salts, see: Mukaiyama, T.; Iwakiri, H.
Chem. Lett. 1985, 1363.
(14) IR (KBr): 3062, 3030 (νCH), 1946, 1873, 1805 (δCH), 1601, 1493
-1
(benzene rings), 1255 (νasSO
2
), 1029 (ν
s
SO
2
2
), 756 (νC-S), 696 (νS-O) cm
.
-
1
1
Cf., Sc(OTf)
3
: 1259 (νasSO
2
), 1032 (ν SO
s
), 769 (νC-S), 647 (νS-O) cm
.
Polystylene: 3062, 3026 (νCH), 1944, 1873, 1803 (δCH), 1600, 1491 (benzene
1
(5) Kobayashi, S.; Nagayama, S. J. Org. Chem. 1996, 61, 2256.
(6) Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1996, 118, 8977.
(7) Donbrow, M. Microcapsules and Nanoparticles in Medicine and
rings) cm-
.
(15) Steric factors (physical envelopment) would also contribute the
remarkable immobilizing ability of polystyrene compared to poor immobiliza-
tion of polybutadiene and polyethylene.
(16) Nitromethane was used in Friedel-Crafts acylation (Scheme 5).
(17) Details are shown in the Supporting Information.
Pharmacy; CRC Press: Boca Raton, FL, 1992.
8) Marty, J. J.; Oppenheim, R. C.; Speiser, P. Pharm. Acta HelV. 1978,
3, 17. Kreuter, J. Pharm. Acta HelV. 1978, 53, 33.
(
5
S0002-7863(97)03928-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 03/17/1998

2986 J. Am. Chem. Soc., Vol. 120, No. 12, 1998
Communications to the Editor
Scheme 3. Aldol Reaction (Batch System)
Scheme 4. Michael Reaction (Batch System)
Scheme 5. Friedel-Crafts Acylation (Batch System)
to have only a low ability to activate aldehydes. On the other
3
hand, MC Sc(OTf) efficiently activated aldehydes, and aldol
Scheme 3),1 cyanation, and allylation
2h
12i,17
reactions of aldehydes
(
proceeded smoothly to give the corresponding aldol, cyanohydrin,
and homoallylic alcohol derivatives in high yields. Michael
reaction of an R,â-unsaturated ketone with a silyl enol ether
Scheme 4)1 and a Diels-Alder reaction of an oxazolidinone
2h
(
Figure 1. Scanning electron microscopy (SEM) micrograph (top) and
11,17
derivative with cyclopentadiene
also worked well using MC
3
scandium energy dispersive X-ray (EDX) map (bottom) of MC Sc(OTf) .
Sc(OTf)
smoothly to produce an aromatic ketone in a good yield (Scheme
3
. Moreover, a Friedel-Crafts acylation proceeded
Scheme 1. Imino Aldol Reaction (Flow System)
12j
5).
Friedel-Crafts alkylation and acylation reactions are
fundamental and important processes in organic synthesis as well
as in industrial chemistry.20 While the alkylation reaction
proceeds in the presence of a catalytic amount of a Lewis acid,
the acylation reaction generally requires more than a stoichio-
metric amount of a Lewis acid, usually aluminum chloride (AlCl
due to consumption of the Lewis acid by coordination to the
aromatic ketone products. It should be noted that MC Sc(OTf)
3
),
3
has high activity in the Friedel-Crafts acylation and can be
recovered easily by simple filtration and reused without loss of
activity.
Scheme 2. Mannich-Type Reaction (Flow System)
In conclusion, we have developed a microencapsulation
technique for binding catalysts to polymers. Utilizing this
technique, an unprecedented polymer-supported, microencapsu-
lated Lewis acid has been prepared. The catalyst thus prepared
has been demonstrated to be effective in many useful carbon-
carbon bond-forming reactions. In all cases, the catalyst was
recovered quantitatively by simple filtration and reused without
loss of the activity. This new technique for binding monomeric
compounds to polymers will be applicable to the preparation of
many other polymer-supported catalysts and reagents.
of the most remarkable and exciting points is that the activating
ability of MC Sc(OTf) for aldimines was revealed to be superior
to that of monomeric Sc(OTf)
The polymer catalyst was recovered quantitatively by simple
filtration and could be reused. The activity of the recovered
catalyst did not decrease even after seven uses (Scheme 1). MC
3
by preliminary kinetic studies.1
7,18
3
Acknowledgment. The authors are grateful to Ms. Yuri Nakasugi
(CREST) for the measurement of SEM micrograph. S.N. thanks the JSPS
fellowship for Japanese Junior Scientists. This work was partially
supported by a Grant-in-Aid for Scientific Research from the Ministry
of Education, Science, Sports, and Culture, Japan, and a SUT Special
Grant for Research Promotion.
Sc(OTf)
3
could also be successfully used in three-component
12f
12d,17
reactions such as Mannich-type (Scheme 2), Strecker,
and
These reactions are known to
quinoline-forming reactions.1
2g,17
be useful for the synthesis of biologically interesting compound
libraries.19
3
It was also found that MC Sc(OTf) was effective for the
Supporting Information Available: Experimental details and reaction
yields (12 pages, print/PDF). See any current masthead page for ordering
information and Web access instructions.
activation of carbonyl compounds. The polymer scandium
5
catalysts such as Nafion-Sc, polyallylscandium trifylamide
6
ditriflate (PA-Sc-TAD) we have previously prepared were found
JA9739289
3
(18) Although the origin of the high activity of MC Sc(OTf) is not clear
at this stage, it was reported that aldimine-Lewis acid complexes were
stabilized by using a polymer-supported Lewis acid. Cf.: Kobayashi, S.;
Nagayama, S. Synlett 1997, 653.
(20) For leading references on Friedel-Crafts acylation, see: Olah, G. A.
Friedel-Crafts Chemistry; Wiley-Interscience: New York, 1973. Heaney,
H. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.; Pergamon Press:
Oxford, 1991; Vol. 2, p 733. Olah, G. A.; Krishnamurti, R.; Prakash, G. K.
S. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.; Pergamon Press:
Oxford, 1991; Vol. 3, p 293.
(
19) Ugi, I.; D o¨ mling, A.; H o¨ rl, W. EndeaVour 1994, 18, 115. Armstrong,
R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc.
Chem. Res. 1996, 29, 123.