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Synlett 2006(7): 1023-1026  
DOI: 10.1055/s-2006-939068
LETTER
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Conjugate Addition of O-Benzylhydroxylamine to α,β-Unsaturated 3-Acyloxazolidin-2-ones Catalyzed by Sc(OTf)3/i-Pr-Pybox Complex

Satoshi Kikuchi, Hiroaki Sato, Shin-ichi Fukuzawa*
Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan
Fax: +81(3)38171895; e-Mail: fukuzawa@chem.chuo-u.ac.jp;
Further Information

Publication History

Received 20 January 2006
Publication Date:
24 April 2006 (online)

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Abstract

The asymmetric conjugate addition of O-benzylhydroxylamine to α,β-unsaturated 3-acyloxazolidin-2-ones was smoothly catalyzed by the Sc(OTf)3/2,6-bis[(S)-4-isopropyloxazolin-2-yl]pyridine (i-Pr-pybox) complex in the presence of MS 4 Å to give the corresponding β-amino acids in good conversions with high enan­tioselectivities (up to 91% ee).

Key words

additional reactions - amino acids - asymmetric catalyst - lanthanides - scandium

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The bidentate-type substrate was known to produce a good enantioselectivity for the reaction using rare-earth Lewis acids, [14] and the corresponding product, the β-amino-3-acyloxazolidin-2-one derivative, could be easily transformed into more useful compounds.

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The reason of this phenomenon was thought to be the failure of the regeneration of the complex between Sc(OTf)3 and i-Pr-pybox at cold temperatures.

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Typical Procedures (Table 2). Under a nitrogen atmosphere, to the suspension of Sc(OTf)3 (10.34 mg, 0.021 mmol) and MS 4 Å (75 mg), which were predried at 180 °C for 3 h under reduced pressure, in CH2Cl2 (5 mL) was added pybox (1a, 6.95 mg, 0.023 mmol) in CH2Cl2 (3 mL) at 0 °C. After stirring for 0.5 h, a solution of 3-crotonoyloxazolidin-2-one (2, 63.61 mg, 0.41 mmol) in CH2Cl2 (3 mL) was added and stirred for an additional 0.5 h. Then, O-benzylhydroxylamine (3, 0.45 mmol), which was used as a CH2Cl2 solution (0.5 M, 0.9 mL, 0.45 mmol), was slowly added dropwise at the same temperature. After 1 h, the reaction was quenched with sat. aq Na2CO3 and the mixture was extracted with CH2Cl2. The combined organic layer was dried over Na2SO4. This organic layer was filtered and evaporated under reduced pressure. The residue was purified by recycling preparative HPLC (GPC column, CHCl3 as eluent) to give the desired products. The enantioselectivity was determined by an HPLC analysis using a chiral column: Chiralpak AD (0.46 cm × 25 cm).
Compound 4a: 1H NMR (300 MHz, CDCl3): δ = 1.17 (d, 3 H, J = 6.45 Hz), 2.87 (dd, 1 H, J = 4.71 Hz, 16.4 Hz), 3.21 (dd, 1 H, J = 8.22 Hz, 16.4 Hz), 3.58-3.67 (m, 1 H), 4.19-4.33 (m, 2 H), 4.67 (s, 2 H), 5.77 (s, 1 H), 7.28-7.37 (m, 5 H). 13C NMR (300 MHz, CDCl3): δ = 18.1, 39.4, 42.2, 52.9, 61.8, 76.3, 127.6, 128.2, 128.3, 137.6, 153.5, 171.9.
Compound 5a: 1H NMR (300 MHz, CDCl3): δ = 1.09 (d, 3 H, J = 6.45 Hz), 2.31 (dd, 1 H, J = 4.08 Hz, 15.2 Hz), 2.36 (dd, 1 H, J = 4.71 Hz, 15.8 Hz), 3.29-3.38 (m, 1 H), 4.52 (s, 2 H), 4.88 (s, 2 H), 5.39 (s, 1 H), 7.24-7.37 (m, 10 H), 9.08 (s, 1 H). 13C NMR (300 MHz, CDCl3): δ = 17.7, 37.7, 52.7, 76.3, 77.9, 128.0, 128.3, 128.4, 128.6, 128.7, 129.1, 135.6, 137.3, 169.2.