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DOI: 10.1055/s-2005-872664
Aldol Reaction of Trimethylsilyl Enolate with Aldehyde Catalyzed by Pyridine N-Oxide as a Lewis Base Catalyst
Publication History
Publication Date:
07 September 2005 (online)
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Abstract
Aldol reaction of trimethylsilyl enolate with aldehydes proceeded in the presence of a catalytic amount of a Lewis base, pyridine N-oxide, and lithium chloride in DMF at room temperature. Not only aryl aldehydes but also alkyl aldehydes provided the aldol products in satisfactory yields. The reaction was mild enough to apply to aldehydes having HO, AcO, THPO, TBDMSO, MeS, pyridyl, or olefinic groups.
Key words
aldol reactions - organomolecular catalysis - pyridine N-oxide - trimethylsilyl ketene acetal - Lewis base
-
1a
Nelson SG. Tetrahedron: Asymmetry 1998, 9: 357 -
1b
Mahrwald R. Chem. Rev. 1999, 99: 1095 -
1c
Machajewski TD.Wong C.-H. Angew. Chem. Int. Ed. 2000, 39: 1352 -
2a
Mukaiyama T. Org. React. 1982, 28: 203 -
2b
Mukaiyama T. Angew. Chem. Int. Ed. 2004, 43: 5590 - 3
Denmark SE.Winter SBD.Su X.Wong K.-T. J. Am. Chem. Soc. 1996, 118: 7404 - 4
Denmark SE.Griedel BD.Coe DM.Schnute ME. 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 -
8a
Mukaiyama T.Fujisawa H.Nakagawa T. Helv. Chim. Acta 2002, 85: 4518 -
8b
Fujisawa H.Mukaiyama T. Chem. Lett. 2002, 182 -
8c
Fujisawa H.Mukaiyama T. Chem. Lett. 2002, 858 -
8d
Nakagawa T.Fujisawa H.Mukaiyama T. Chem. Lett. 2003, 32: 462 - 9
Nakagawa T.Fujisawa H.Mukaiyama T. Chem. Lett. 2004, 33: 92 -
10a
Chelucci G.Murineddu G.Pinna GA. Tetrahedron: Asymmetry 2004, 15: 1373 -
10b
Hoshi T.Katano M.Nozawa E.Suzuki T.Suzuki T.Hagiwara H. Tetrahedron Lett. 2004, 45: 3489 -
10c
Tao B.Lo MM.-C.Fu GC. J. Am. Chem. Soc. 2001, 23: 353 - Chiral pyridine N-oxide has been used in enantioselective aldol reaction of trichlorosilyl enol ether:
-
11a
Denmark SE.Fan Y. J. Am. Chem. Soc. 2002, 124: 4233 -
11b
Nakajima M. J. Synth. Org. Chem., Jpn. 2003, 61: 1081 - 12
Sojka SA. J. Org. Chem. 1979, 44: 707 - 13 Retro-aldol reaction was not a problem since the initial product was a silylether of 3, see:
Rodriguez MJ.Zweifel MJ. Tetrahedron Lett. 1996, 37: 4301 - 14
Nakajima M.Sato M.Shiro M.Hashimoto S. J. Am. Chem. Soc. 1998, 120: 6419 - 15
Sato K.Kira M.Sakurai H. Tetrahedron Lett. 1989, 30: 4375 - 18
Mikami K.Matsumoto S.Ishida A.Takamuku S.Suenobu T.Fukuzumi S. J. Am. Chem. Soc. 1995, 117: 11134
References
Typical experimental procedure: To a stirred solution of pyridine N-oxide (3.8 mg, 0.04 mmol) and LiCl (3.4 mmol, 0.08 mmol) in DMF (1.5 mL) were added benzaldehyde 2 (R = Ph) (42 µL, 0.4 mmol) and trimethylsilyl ketene acetal 1 (105 µL, 0.52 mmol) at r.t. under a nitrogen atmosphere. After stirring for 5 h, the reaction was quenched by the addition of 1 N aq HCl. The product was extracted with EtOAc twice. The combined organic layer was washed with water, brine, and evaporated to dryness. The residue was purified by medium-pressure LC (EtOAc-hexane, 1:2) to afford aldol product 3 (R = Ph) (92 mg, 81%) as a solid.
17All new compounds have satisfactory analytical data including 1H NMR, 13C NMR and IR spectra and HRMS.