C O M M U N I C A T I O N S
Table 3. Tandem Michael Reaction-Protection Using the HT and
acrylonitrile occurred at the base sites of the Pd/HT to afford
2-carbomethoxy-2-benzyl glutaronitrile in an excellent overall yield
(v).16 To the best of our knowledge, these are the first demonstra-
tions of one-pot synthesis consisting of more than four catalytic
acid and base reactions.
Ti4+-mont in a Single Pota
In conclusion, isolated catalytically active centers could be
created based on clay materials for realization of a variety of acid-
base tandem reactions. This protocol has several advantages: (I)
the ease of preparing the solid catalysts, (II) high catalytic activities,
(III) wide applicability to several acid or base reactions, (IV) simple
workup procedure, and (V) reusability. Our concept can be applied
to other various one-pot incompatible systems and make a contribu-
tion toward the creation of environmentally inspired chemical
processes through the promotion of multiple reactions in a single
reactor.
conditions of
Michael reaction
Isolated
yield (%)
entry
acceptor
donor
product
1
4a
4a
4b
4c
4c
4d
5a
5b
5a
5a
5c
5d
40 °C, 2 h
40 °C, 3 h
50 °C, 3 h
50 °C, 3 h
100 °C, 10 h
40 °C, 3 h
6a
6b
6c
6d
6e
6f
89
89
86
70
82
64
2
3
4
5b,c
6c,d
Supporting Information Available: Details of experimental
procedures and acknowledgment (PDF). This material is available free
a Acceptor (1 mmol), donor (2 mL), Ti4+-mont (0.15 g), HT (0.1 g).
After the completion of Michael reaction, ethane-1,2-diol (1.5 mmol) and
toluene (10 mL) were added followed by acetalization under Dean-Stark
conditions for 1 h. b Donor (1.2 mmol) was used. c Toluene (2 mL) was
used as solvent for Michael reaction. d Donor (1 mmol) and ethane-1,2-
diol (1.1 mmol) were used.
References
(1) Hall, N. Science 1994, 266, 32.
Scheme 1
(2) For excellent reports of one-pot reactions, see: (a) Koeller, K. M.; Wong,
C.-H. Chem. ReV. 2000, 100, 4465. (b) Kawasaki, T.; Yamamoto, Y. J.
Org. Chem. 2002, 67, 5138. (c) Balme, G.; Bossharth, E.; Monteiro, N.
Eur. J. Org. Chem. 2003, 4101. (d) Choudary, B. M.; Chowdari, N. S.;
Madhi, S.; Kantam, M. L. J. Org. Chem. 2003, 68, 1736. (e) Nicolaou,
K. C.; Montagnon, T.; Snyder, S. A. Chem. Commun. 2003, 551.
(3) (a) Cohen, B. J.; Kraus, M. A.; Patchornik, A. J. Am. Chem. Soc. 1977,
99, 4165. (b) Cainelli, G.; Contento, M.; Manescalchi, F.; Regnoly, R. J.
Chem. Soc., Perkin Trans. 1 1980, 2516. (c) Gelman, F.; Blum, J.; Avnir,
D. J. Am. Chem. Soc. 2000, 122, 11999. (d) Gelman, F.; Blum, J.; Avnir,
D. Angew. Chem., Int. Ed. 2001, 40, 3647. (e) Gelman, F.; Blum, J.; Avnir,
D. J. Am. Chem. Soc. 2002, 124, 14460.
(4) For acidic clays: (a) Ebitani, K.; Kawabata, T.; Nagashima, K.; Mizugaki,
T.; Kaneda, K. Green Chem. 2000, 2, 157. (b) Kawabata, T.; Mizugaki,
T.; Ebitani, K.; Kaneda, K. Tetrahedron Lett. 2001, 42, 8329. (c)
Kawabata, T.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc.
2003, 125, 10486. (d) Kawabata, T.; Kato, M.; Mizugaki, T.; Ebitani, K.;
Kaneda, K. Chem. Lett. 2003, 32, 648. (e) Kawabata, T.; Mizugaki, T.;
Ebitani, K.; Kaneda, K. Tetrahedron Lett. 2003, 44, 9205. For basic
clays: (f) Yamaguchi, K.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda,
K. J. Org. Chem. 2000, 65, 6897. (g) Motokura, K.; Nishimura, D.; Mori,
K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2004, 126,
5662.
tion of the aldehyde during this one-pot reaction (entry 7). On the
contrary, the use of n-hexanal itself in place of hexanal dimethyl-
acetal resulted in the desired product in 71% GC yield together
with 2-butyl-2-octenal. The solid mixture consisting of the Ti4+
-
mont and HT catalysts was easily recovered by simple filtration
and then could be reused at least five times with retention of high
catalytic activity and selectivity.13 Clearly, mutual neutralization
of the acid and base catalysts can be aVoided using this system in
a single reactor.
(5) For mont-catalyzed organic synthesis, see: (a) Pinnavaia, T. J. Science
1983, 220, 365. (b) Laszlo, P. Acc. Chem. Res. 1986, 19, 121. (c) Izumi,
Y.; Onaka, M. AdV. Catal. 1992, 38, 245.
(6) For HT catalysts, see: (a) Sels, B. F.; De Vos, D. E.; Buntinx, M.; Pierard,
F.; Kirsch-De Mesmaeker, A.; Jacobs, P. A. Nature 1999, 400, 855. (b)
Sels, B. F.; De Vos, D. E.; Jacobs, P. A. Catal. ReV. 2001, 43, 443. (c)
Choudary, B. M.; Madhi, S.; Chowdari, N. S.; Kantam, M. L.; Sreedhar,
B. J. Am. Chem. Soc. 2002, 124, 14127. (d) Palomares, A. E.; Prato, J.
G.; Rey, F.; Corma, A. J. Catal. 2004, 221, 62.
The present catalyst system is also applicable to tandem Michael
reaction4g and acetalization,4b as summarized in Table 3. These
reactions gave excellent yields of nitrodioxolanes (entries 1-4),
which are highly useful precursors for several nitro-group transfer
reactions.14 For example, nitromethane underwent the Michael
reaction with methyl vinyl ketone, followed by acetalization with
ethane-1,2-diol to afford an 89% yield of 2-methyl-2-(3-nitropro-
pyl)-1,3-dioxolane (entry 1), whereas the conventional two-step
method gave less than 70% yield.14b Also, the tandem reaction of
dimethyl malonate with 2-cyclohexene-1-one readily proceeded
(entry 5), and in the case of a â-ketoester, chemoselective
acetalization toward an aldehyde function occurred to give a
protected Michael adduct (entry 6).
(7) The Ti4+-mont and HT catalysts showed higher activities than those of
other solid acid (see ref 4b) and base catalysts (see Supporting Informa-
tion), such as zeolites and MgO.
(8) The first path of the deacetalization proceeded using water adsorbed on
the Ti4+-mont.
(9) (a) Carrigan, M. D.; Sarapa, D.; Smith, R. C.; Wieland, L. C.; Mohan, R.
S. J. Org. Chem. 2002, 67, 1027. (b) Dalpozzo, R.; De Niro, A.; Maiuolo,
L.; Procopio, A.; Tagarelli, A.; Sindona, G.; Bartoli, G. J. Org. Chem.
2002, 67, 9093.
(10) The reaction of simple alkylnitriles with high pKa values (∼31) did not
occur under the present conditions.
(11) The estimated turnover numbers of acid and base sites were calculated to
be 25 and 7, respectively; see Supporting Information.
(12) Yamakawa, T.; Kagechika, H.; Kawachi, E.; Hashimoto, Y.; Shudo, K.
J. Med. Chem. 1990, 33, 1430.
The potential benefits of using these clay catalysts together are
highlighted by the development of novel one-pot synthetic processes
(Scheme 1). Epoxynitrile, an intermediate for the synthesis of var-
ious heterocyclic compounds,15 was successfully obtained using
methanol, cyanoacetic acid, 1, and hydrogen peroxide in four se-
quential acid and base reactions, namely, esterification (i),4e deace-
talization (ii), aldol reaction (ii), and epoxidation (iii),4f in a single
reactor. We also succeeded in a one-pot synthesis of glutaronitrile
using the Ti4+-mont and Pd/HT catalysts. After reduction of the
unsaturated nitrile under 1 atm of H2 (iv), Michael reaction with
(13) In the reaction of methyl cyanoacetate with 1, the yields of the first, second,
and fifth runs were 95, 95, and 90%, respectively.
(14) (a) Laronze, J. Y.; Laronze, J.; Patigny, D.; Levy, J. Tetrahedron Lett.
1986, 27, 489. (b) Ulrich, W.-R.; Scheufler, C.; Fuchss, T.; Senn-Bilfinger,
J. Eur. Pat. Appl. 0151486, Jul 19, 2001.
(15) (a) Ammadi, F.; Boukhris, S.; Souizi, A.; Coudert, G. Tetrahedron Lett.
1999, 40, 6517. (b) Gaz, A.; Souizi, A.; Coudert, G. Synth. Commun.
1999, 29, 3459.
(16) The Pd/HT has both surface basicity and hydrogenation ability. For details
of the bifunctional catalysis of the Pd/HT, see: Motokura, K.; Fujita, N.;
Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. Tetrahedron Lett., in
press.
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