5
46
S. Kobayashi et al.
LETTER
as deamination and aldol products were not obtained at
(2) (a) Kobayashi, S. Chem. Lett. 1991, 2187. (b) Kobayashi, S.
Synlett 1994, 689. (c) Kobayashi, S. Organic Reactions in
Water, Grieco, P. Ed. Chapman & Hall, 1998, p. 262.
10
all. Other catalysts such as Yb(OTf) and Cu(OTf) were
3
2
1
1
also found to be effective in this reaction. We then tested
other examples and the results are summarized in Table 1.
Aromatic aldehydes as well as heterocyclic, a,b-unsatur-
ated, aliphatic aldehydes, and a glyoxal worked well to af-
ford the desired adducts in high yields. It is noteworthy
that various types of aliphatic aldehydes reacted smoothly
to give the corresponding b-amino ketone derivatives in
high yields. For silyl enolates, not only ketone-derived si-
lyl enol ethers but also thioester- and ester-derived ketene
silyl acetals worked well.
(d) Kobayashi, S. Eur. J. Org. Chem. 1999, 15.
(
3) Kobayashi, S.; Wakabayashi, T.; Nagayama, S.; Oyamada, H.
Tetrahedron Lett. 1997, 38, 4559. See also, Kobayashi, S.;
Wakabayashi, T.; Oyamada, H. Chem. Lett. 1997, 831.
(4) Kleinnmann, E. F. In Comprehensive Organic Synthesis
Trost, B. M. Ed.; Pergamon Press: New York, 1991; Vol. 2,
Chapter 4.1.
(
(
(
5) (a) Kobayashi, S.; Araki, M.; Yasuda, M. Tetrahedron Lett.
1995, 36, 5773. (b) Annunziata, R.; Cinquini, M.; Cozzi, F.;
Molteni, V.; Schupp, O. J. Org. Chem. 1996, 61, 8293.
6) For aqueous Mannich-type reactions, (a) Kobayashi, S.;
Ishitani, H. J. Chem. Soc., Chem. Commun. 1995, 1379.
The products were readily converted to free b-amino
ketones and esters. Thus, treatment of the products with
cerium ammonium nitrate (CAN) in acetonitrile-water
(
b) Loh, T.-P; Wei, L.-L. Tetrahedron Lett. 1998, 39, 323.
7) We have recently developed three-component coupling
reactions of aldehydes, amines, and allyltributyltin in micellar
systems. Kobayashi, S.; Busujima, T.; Nagayama, S. J. Chem.
Soc., Chem. Commun. 1998, 19. It is noted that silyl enolates
are much easier to hydrolyze than allyltributyltin in water. See
also, Kobayashi, S.; Busujima, T.; Nagayama, S. J. Chem.
Soc., Chem. Commun. 1998, 981.
(9:1) at rt induced smooth deprotection of the 2-methoxy-
phenylamino group to give free b-amino carbonyl com-
1
2,13
pounds.
In summary, three-component coupling reactions of alde-
hydes, amines, and silyl enolates were successfully per-
(8) A typical experimental procedure is as follows. To a 35 mM
3
formed in micellar systems using Ln(OTf) or Cu(OTf)2
water solution of SDS (3 ml) and Sc(OTf) (0.025 mmol) were
3
as a catalyst. The reactions proceeded cleanly with a wide
added an amine (0.5 mmol), a silyl enolate (0.5 mmol), and an
aldehyde (0.55-0.65 mmol) successively, and the mixture was
stirred at rt. After 5 h, the mixture was diluted with water and
ethyl acetate. The aqueous layer was extracted with ethyl
acetate, and the combined organic layer was dried, filtered,
and concentrated. The crude adduct was purified by column
chromatography on silica gel to afford the pure desired b-
amino carbonyl compound.
substrate range in water without using any organic sol-
vents. This benign process will be applied to the synthesis
of many b-amino carbonyl compounds including biologi-
cally interesting compounds, and such projects are now in
progress in our laboratory.
(
9) Only a trace amount of the product was obtained without SDS
Acknowledgement
under the same reaction conditions.
(
(
(
10) Similar reactions performed in organic solvents sometimes
induced certain amounts of deamination products.
11) Kobayashi, S.; Nagayama, S.; Busujima, T. J. Am. Chem. Soc.
This work was partially supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports, and Cul-
ture, Japan. S. N. thanks the JSPS fellowship for Japanese Junior
Scientists.
1
998, 120, 8287.
12) Kronenthal, D. R.; Han, C. Y.; Taylor, M. K. J. Org. Chem.
982, 47, 2765.
(13) Ishitani, H.; Ueno, M.; Kobayashi, S. J. Am. Chem. Soc. 1997,
19, 7153.
14) Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1997, 119,
0049.
1
References and Notes
1
(
1) (a) Grieco, P. Ed. Organic Reactions in Water, Chapman &
Hall, 1998. (b) Li, C.-J.; Chan, T.-H. Organic Reactions in
Aqueous Media, Wiley: New York, 1997. (c) Lubineau, A.;
Augé, J.; Queneau, Y. Synthesis 1994, 741. (d) Li, C.-J. Chem.
Rev. 1993, 93, 2023. (e) Reissig, H.-U. In Organic Synthesis
Highlights, Waldmann, H. Ed. VCH: Weinheim, 1991, p 71.
(
1
Article Identifier:
437-2096,E;1999,0,05,0545,0546,ftx,en;Y03499ST.pdf
1
(f) Einhorn, C.; Einhorn, J. Synthesis 1989, 787.
Synlett 1999, No. 5, 545–546 ISSN 0936-5214 © Thieme Stuttgart · New York