in Aid for Scientific Research from Japan Society of the
Promotion of Science.
Notes and references
† A typical experimental procedure is as follows: benzaldehyde (0.25
mmol), aniline (0.25 mmol), and the ketene silyl acetal (0.375 mmol)
derived from methyl isobutyrate were successively added to a mixture of
PS–SO3H (0.12 mmol g21, 0.0025 mmol) in degassed water (1.5 mL) at 0
°C. The reaction mixture was stirred for 2 h at the same temperature, and
then quenched with sat. aq. NaHCO3 (5 mL). The polymer was filtered and
washed with water and dichloromethane. The organic layer was dried over
Na2SO4, and evaporated. The mixture was purified by preparative TLC on
silica gel to give the desired product in 83% yield. All experiments were
carried out using PS–SO3H whose loading was 0.12 mmol g21 except for
some experiments shown in Table 1.
Scheme 1 PS–SO3H-catalyzed direct Mannich-type reactions in water.
also achieved using this catalytic system in water (Scheme 1).7
In addition, it was also found that a vinyl ether reacted with an
aldehyde and an amine in the presence of 1 mol% PS–SO3H in
water at 30 °C for 6 h to give the Mannich-type adduct in good
yield (eqn. 1), although the direct Mannich-type reaction using
acetone as a nucleophile proceeded in 24% yield under the same
reaction conditions. It is noted that these three-component
reactions are an atom-economical and environmentally friendly
synthetic method as well as a useful method for facile synthesis
of b-amino ketone libraries.3
1 Organic Synthesis in Water; ed. P. A. Grieco, Blackie Academic and
Professional, London, 1998; C.-J. Li and T.-H. Chan, Organic
Reactions in Aqueous Media, John Wiley & Sons, New York, 1997; U.
M. Lindström, Chem. Rev., 2002, 102, 2751; S. Kobayashi and K.
Manabe, Acc. Chem. Res., 2002, 35, 209.
2 S. V. Ley, I. R. Baxendale, R. N. Bream, P. S. Jackson, A. G. Laech, D.
A. Longbottom, M. Nesi, J. S. Scott, R. I. Storer and S. J. Taylor, J.
Chem. Soc., Perkin Trans. 1, 2000, 3815; C. A. McNamara, M. J. Dixon
and M. Bradley, Chem. Rev., 2002, 102, 3275; D. E. Bergbreiter, Chem.
Rev., 2002, 102, 3345.
3 S. Kobayashi, Curr. Opin. Chem. Biol., 2000, 4, 338; S. Kobayashi and
R. Akiyama, Chem. Commun., 2003, 449.
4 For recent examples of polymer-supported catalysts which work in
water, see: S. Nagayama and S. Kobayashi, Angew. Chem. Int. Ed.,
2000, 39, 567; D. E. Bergbreiter and Y.-S. Liu, Tetrahedron Lett., 1997,
38, 7843; D. E. Bergbreiter, B. L. Case, Y.-S. Liu and J. W. Caraway,
Macromolecules, 1998, 31, 6053; C.-W. Chen, M.-Q. Chen, T. Serizawa
and M. Akashi, Chem. Commun., 1998, 831; H. Danjo, D. Tanaka, T.
Hayashi and Y. Uozumi, Tetrahedron, 1999, 55, 14341; Y. Uozumi and
K. Shibatomi, J. Am. Chem. Soc., 2001, 123, 2919; T. Sakamoto and C.
J. Pac, Tetrahedron Lett., 2000, 41, 10009; Y. M. A. Yamada, M.
Ichinohe, H. Takahashi and S. Ikegami, Org. Lett., 2001, 3, 1837; Y.
Masaki, T. Yamada and N. Tanaka, Synlett, 2001, 1311.
5 K. Manabe and S. Kobayashi, Adv. Synth. Catal., 2002, 344, 270; S.
Iimura, K. Manabe and S. Kobayashi, Org. Lett., 2003, 5, 101.
6 F. F. Blicke, Org. React., 1942, 1, 303; E. F. Kleinnmann, in
Comprehensive Organic Synthesis, ed. B. M. Trost, Pergamon, New
York, 1991, vol. 2, ch. 4.1.
(1)
Finally, we conducted another three-component Mannich-
type reaction in water using a phosphite as a nucleophile (eqn.
2).12,13 This type of reaction is also an attractive method to
produce a-amino phosphonates, which are not only an im-
portant class of biologically active compounds but also
structural analogues to a-amino acids.14 The reaction proceeded
smoothly using 1 mol% PS–SO3H in water to afford the a-
amino phosphonate in good yield.
7 K. Manabe, Y. Mori and S. Kobayashi, Synlett, 1999, 1401; K. Manabe
and S. Kobayashi, Org. Lett., 1999, 1, 1965; K. Manabe, Y. Mori and S.
Kobayashi, Tetrahedron, 2001, 57, 2537.
8 T. Akiyama, J. Takaya and H. Kagoshima, Synlett, 1999, 1426.
9 For examples of Mannich-type reactions in water using polymer-
supported scandium catalysts, see: M. T. Reetz and D. Giebel, Angew.
Chem., Int. Ed., 2000, 39, 2498; W. Gu, W.-J. Zhou and D. L. Gin,
Chem. Mater., 2001, 13, 1949.
10 Mannich-type reactions in organic solvents using a cation-exchange
resin, see: M. Shimizu and S. Itohara, Synlett, 2000, 1828; M. Shimizu,
S. Itohara and E. Hase, Chem. Commun., 2001, 2318.
(2)
In summary, several types of three-component Mannich-type
reactions were efficiently catalyzed by hydrophobic polysty-
rene-supported sulfonic acid (PS–SO3H) in water under mild
conditions. This is the first example of C–C and C–P bond-
forming reactions in water as the sole solvent using this type of
catalyst. It should be noted that PS–SO3H has high catalytic
activity in water, and that only 1 mol% of PS–SO3H is enough
to catalyze the reactions in most cases. These results not only
provide a new aspect of catalytic organic reactions in water but
also extend the utility of hydrophobic PS–SO3H in organic
synthesis in water to lead to environmentally benign proc-
esses.
11 The catalyst could be reused at least three times without quenching with
base in this reaction. The yields were 1st: 79%, 2nd: 79%, 3rd: 78%,
respectively.
12 For recent examples of this type of transformation, see: K. Manabe and
S. Kobayashi, Chem. Commun., 2000, 669; C. Qian and T. Huang, J.
Org. Chem., 1998, 63, 4125; B. C. Ranu, A. Hajra and U. Jana, Org.
Lett., 1999, 1, 1141; S.-G. Lee, J. H. Park, J. Kang and J. K. Lee, Chem.
Commun., 2001, 1698; B. C. Ranu and A. Hajra, Green Chemistry,
2002, 4, 551; S. Chandrasekhar, Ch. Narsihmulu, S. S. Sultana, B.
Saritha and S. J. Prakash, Synlett, 2003, 505.
13 The yield was 21% when the reaction was carried out without the
catalyst under the same conditions.
14 For a recent review: S. C. Field, Tetrahedron, 1999, 55, 2537.
This work was partially supported by CREST and SORST,
Japan Science and Technology Corporation (JST), and a Grant-
CHEM. COMMUN., 2003, 1644–1645
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