Angewandte
Chemie
Table 1: Results (% conversion) of catalytic reaction sequences carried
out in one pot with multiple opposingcatalysts.
and this methodology may be further expanded almost
without limit through other means of catalyst separation,
such as membrane encapsulation.[16]
Catalyst
Conv. [%]
Conv. [%]
Blue Sequence 1!2!3[a]
solid acid and solid base
solid acid
1!2
100
100
0
2!3
Received: September 29, 2005
Revised: November 9, 2005
Published online: March 10, 2006
100
0
solid base
0
solid acid and homogeneous base
solid base and homogeneous acid
homogeneous acid and base
0
0
0
0
0
0
Keywords: acidity · heterogeneous catalysis ·
magnetic properties · nanostructures · synthetic methods
.
Green Sequence 2!3!4[a]
2!3
3!4
solid base and Pt/Al2O3
100
100
Violet Sequence 1!2!3!4[a]
1!3
3!4
78
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[3] Simplified workup of the reaction and purification of the product
in sequences of reactions can be achieved by following the
example of Ley and co-workers, who have used a variety of
polymer-supported catalysts, reagents, and scavengers in com-
plex reaction sequences. For example, see: a) I. R. Baxendale,
S. V. Ley, C. Piutti, Angew. Chem. 2002, 114, 2298; Angew. Chem.
Int. Ed. 2002, 41, 2194; b) R. I. Storer, T. Takemoto, P. S. Jackson,
S. V. Ley, Angew. Chem. 2003, 115, 2625; Angew. Chem. Int. Ed.
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Caldarelli, A. Massi, M. Nesi, Farmaco 2002, 57, 321.
[4] a) J. C. Wasilke, S. J. Obrey, R. T. Baker, G. C. Bazan, Chem.
Rev. 2005, 105, 1001, 2005; b) L. F. Tietze, U. Beifuss, Angew.
Chem. 1993, 105, 137; Angew. Chem. Int. Ed. Engl. 1993, 32, 131;
c) L. F. Tietze, M. E. Lieb, Curr. Opin. Chem. Biol. 1998, 2, 363;
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Walton, J. Chem. Soc. Perkin Trans. 1 2001, 3215; f) P. J. Parsons,
C. S. Penkett, A. J. Shell, Chem. Rev. 1996, 96, 195; g) K. C.
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Chem. Rev. 2000, 69, 1001; i) J. M. Lee, Y. Na, H. Han, S. Chang,
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Martinez, J. Am. Chem. Soc. 1994, 116, 10847; k) S. E. Denmark,
A. Thorarensen, Chem. Rev. 1996, 96, 137; l) M. Makkee,
A. P. G. Kieboom, H. Van Bekkum, J. Chem. Soc. Chem.
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Van Bekkum, Carbohydr. Res. 1985, 138, 237; p) G. H. Posner,
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Le Ray, J. E. Bäckvall, J. Am. Chem. Soc. 1999, 121, 1645.
[5] Using solid catalysts, a catalyst mixture may be recovered
although its separation into pure components is generally not
possible using published methodologies. a) F. Gelman, J. Blum,
D. Avnir, J. Am. Chem. Soc. 2000, 122, 11999; b) F. Gelman, J.
Blum, D. Avnir, Angew. Chem. 2001, 113, 3759; Angew. Chem.
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Schuman, D. Avnir, J. Sol-Gel Sci. Technol. 2003, 26, 43; e) F.
Gelman, J. Blum, D. Avnir, New J. Chem. 2003, 27, 205; f) K.
Motokura, N. Fujita, K. Mori, T. Mizugaki, K. Ebitani, K.
Kaneda, J. Am. Chem. Soc. 2005, 127, 9674; g) B. Helms, S. J.
Guillaudeau, Y. Xie, M. McUrdo, C. J. Hawker, J. M. J. FrØchet,
solid acid, solid base, and Pt/Al2O3
100
(100[b])
Gray Sequence 1!2!5a+5b[a]
1!2
2!5a+5b
100
(4:1 5a/5b)
solid acid and solid base
100
Red Sequence 1!2!6a+6b[a]
1!2
2!6a+6b
82
(26:1 6a/6b)
solid acid and solid base
100
[a] See Figure 1 for reaction sequences. [b] In the absence of
a
membrane. In this case, the Pt/Al2O3 and the polymer resin were
obtained after the reaction as a mixture, although the magnetic catalyst
could be isolated.
reactions was demonstrated by the conversion of 1 to 2 to 5a
and 5b (Figure 1, gray box) using the same acid and base
catalysts. By adding the magnetic nanoparticles used in the
first two reaction sequences (1!2!3 and 2!3!4) and the
acidic resin used in the first reaction sequence (1!2!3) to
new reagents in a single vessel, the synthesis of 5a and 5b was
achieved with complete conversion of 1 into 5a and 5b. Note
that this sequence represents the third use of a single sample
of magnetic catalyst and the second use of a single sample of
the acid catalyst. Similarly, products 6a and 6b were prepared
in another one-pot reaction (Figure 1, red box) with excellent
results.[14]
In summary, we have shown that excellent control of a
reaction sequence using chemical catalysts can be achieved by
1) using combinations of a few versatile catalysts that can be
used in a variety of reactions, with recovery of the catalyst in
pure form after the reaction; 2) compartmentation of cata-
lytic sites to allow for use of catalysts that would self-quench
in homogeneous media;[5] and 3) regulation of the reaction
pathway by manipulating the reaction conditions, including
control of the catalysts and reagents that are present. The
combination of magnetically and gravimetrically recoverable
catalysts allowed the first successful application of opposing
catalysts to multistep, one-pot catalytic reactions including
the ability to steer the direction of the reaction at each step,
all with recovery of each individual catalyst after use. The
successful use of the recovered catalysts in combination with
other catalysts in subsequent, unrelated reactions showed the
versatility of this approach.[15] A library of magnetically and
gravimetrically recoverable catalysts could thus be generated
and used in a variety of one-pot multistep catalytic reactions,
Angew. Chem. Int. Ed. 2006, 45, 2209 –2212
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