H. Hagiwara et al. / Tetrahedron Letters 47 (2006) 5371–5373
5373
Eds.; Pergamon: Oxford, UK, 1991; Vol. 2, p 133, and
related Chapters; Nelson, S. G. Tetrahedron: Asymmetry
1998, 9, 357; Mahrwald, R. Chem. Rev. 1999, 99, 1095;
Machajewski, T. D.; Wong, C.-H. Angew. Chem., Int. Ed.
2000, 39, 1352.
OTMS
(0.1 eq)
N
N
Ph
OH
O
LiCl (0.2 eq), DMF
r.t. or microwave
4
+
R
Ph
Acidic work-up
2. Mukaiyama, T. Org. React. 1982, 28, 203; Angew. Chem.,
Int. Ed. 2004, 43, 5590.
RCHO 2
5
3. Denmark, S. E.; Winter, S. B. D.; Su, X.; Wong, K.-T.
J. Am. Chem. Soc. 1996, 118, 7404.
Scheme 2. Aldol reaction of trimethylsilyl enolates catalyzed by N-
methylimidazole.
4. Denmark, S. E.; Griedel, B. D.; Coe, D. M.; Schnute, M.
E. J. Am. Chem. Soc. 1994, 116, 7026.
5. Genisson, Y.; Gorrichon, L. Tetrahedron Lett. 2000, 41,
4881.
6. Matsukawa, S.; Okano, N.; Imamoto, T. Tetrahedron
Lett. 2000, 41, 103.
7. Miura, K.; Nakagawa, T.; Hosomi, A. J. Am. Chem. Soc.
2002, 124, 536.
8. (a) Mukaiyama, T.; Fujisawa, H.; Nakagawa, T. Helv.
Chim. Acta 2002, 85, 4518; (b) Fujisawa, H.; Mukaiyama,
T. Chem. Lett. 2002, 182; (c) Fujisawa, H.; Mukaiyama, T.
Chem. Lett. 2002, 858; (d) Nakagawa, T.; Fujisawa, H.;
Mukaiyama, T. Chem. Lett. 2003, 32, 462.
Table 3. Reaction of silyl enolate 1 or 4 with a variety of aldehydes 2a
under microwave heating
Entry
Enolate (equiv)
Aldehyde 2
Yieldb (%)
1
2
3
4
5
6
1 (1.5)
Benzaldehyde
82
85
74
88
78
77
p-Anisaldehyde
Hydrocinnamaldehyde
Benzaldehyde
p-Chlorobenzaldehyde
Citronellal
4 (5)
a The reaction was carried out in the presence of N-methylimidazole
(0.1 equiv) and LiCl (0.2 equiv) in DMF under microwave irradia-
tion. The temperature ramped from room temperature to 90 °C and
kept at the temperature for 30 min. The irradiation was repeated
once again for 30 min. The temperature was monitored by radiation
thermometer.
9. Nakagawa, T.; Fujisawa, H.; Mukaiyama, T. Chem. Lett.
2004, 33, 92.
10. Tao, B.; Lo, M. M.-C.; Fu, G. C. J. Am. Chem. Soc. 2001,
23, 353; Denmark, S. E.; Fan, Y. J. Am. Chem. Soc. 2002,
124, 4233; Nakajima, M. J. Synth. Org. Chem., Jpn. 2003,
61, 1081; Chelucci, G.; Murineddu, G.; Pinna, G. A.
Tetrahedron: Asymmetry 2004, 15, 1373; Hoshi, T.;
Katano, M.; Nozawa, E.; Suzuki, T.; Suzuki, T.; Hagiw-
ara, H. Tetrahedron Lett. 2004, 45, 3489.
b Yield of the isolated pure product based on aldehyde 2.
which would be useful not only for large-scale prepara-
tion but also for transformation of multifunctional sub-
strates for natural products syntheses.
11. Hagiwara, H.; Inoguchi, H.; Fukushima, M.; Hoshi, T.;
Suzuki, T. Synlett 2005, 2388.
12. Chuit, C.; Corriu, R. J. P.; Reye, C.; Young, J. C. Chem.
Rev. 1993, 93, 1371.
13. Typical experimental procedure: To a stirred solution of
N-methylimidazole (5 lL, 0.045 mmol) and anhydrous
LiCl (4 mg, 0.08 mmol) in DMF (1.5 mL) were added
benzaldehyde 2 (R = Ph) (42 lL, 0.4 mmol) and trimethyl-
silyl ketene acetal 1 (125 lL, 0.6 mmol) at room temper-
ature under nitrogen atmosphere. After being stirred for
10 h, the reaction was quenched by the addition of a little
amount of 1 N aq HCl. The product was extracted with
ethyl acetate twice. The combined organic layer was
washed with water and brine and evaporated to dryness.
The residue was purified by medium-pressure LC (eluent:
ethyl acetate–n-hexane = 1:2) to afford aldol product 3
(R = Ph) (78 mg, 91%) as a solid.
Acknowledgements
This work was partially supported by Grant-in-Aid for
Scientific Research on Priority Areas (18032031 and
18045015 for H.H.) from The Ministry of Education,
Culture, Sports, Science and Technology (MEXT).
References and notes
1. For review: Heathcock, C. H. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Heathcock, C. H.,