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Synlett 2009(18): 3007-3010  
DOI: 10.1055/s-0029-1218001
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Asymmetric α-Amination of Chiral Protected β-Hydroxyaldehydes Catalyzed by Proline

Ramzi Ait-Youcef, Kamal Sbargoud, Xavier Moreau, Christine Greck*
Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles St-Quentin-en-Yvelines, 45, Avenue des Etats-Unis, 78035 Versailles Cedex, France
Fax: +33(1)39254452; e-Mail: greck@chimie.uvsq.fr;
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Publication History

Received 16 July 2009
Publication Date:
08 October 2009 (online)

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Abstract

Proline-catalyzed α-amination of a variety of chiral β-hydroxyaldehydes followed by reduction step afforded the corresponding chiral 2-hydrazino-1,3-diols in good yields, enantioselectivities and diastereoselectivities.

Key words

amination - organocatalysis - diastereoselectivity - β-­hydroxyaldehyde - 2-hydrazino-1,3-diol - azodicarboxylate

    References and Notes

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10

3-tert-Butyldimethylsilyloxybutanal (1) was synthesized in two steps (TBS protection and DIBAL-H reduction of the ester moiety) from ethyl 3-hydroxybutyrate commercially available in both enantiomeric forms.

12

General Procedure for the Organocatalytic α-Amination: Dibenzylazodicarboxylate (1 mmol) and d- or l-proline (0.2 mmol, 20 mol%) in MeCN (10 mL) were treated with an aldehyde (1.5 mmol) at r.t. The reaction mixture was stirred at this temperature until the yellow color of the azodicarboxylate had disappeared. The mixture was treated with EtOH (10 mL) and NaBH4 (40 mg) and was stirred for 5 min at 0 ˚C. The reaction was worked up with aq NH4Cl solution and EtOAc. The organic layers were dried (MgSO4), filtered, and concentrated. Medium-pressure column chromatography on silica gel with EtOAc-pentane mixture (1:4) gave the desired anti- or syn-2-hydrazino-1,3-diol as a single diastereomer.

15

Characterization of Selected Compounds:
Compound 2: ¹H NMR (300 MHz, CDCl3): δ = 0.01-0.05 (m, 6 H), 0.86 (s, 9 H), 1.08-1.16 (m, 3 H), 3.51-3.99 (m, 4 H), 4.15-4.33 (m, 1 H), 5.16-5.29 (m, 4 H), 6.54 (s, 1 H), 7.28-7.37 (m, 10 H). ¹³C NMR (75 MHz, CDCl3): δ = -5.1, -4.3, 17.7, 21.1, 25.6, 59.1, 59.6, 66.3, 67.0, 67.4, 68.1, 68.3, 68.5, 127.5, 127.7, 128.0, 128.1, 128.3, 128.4, 128.5, 135.0, 135.4, 135.6, 156.0, 157.0, 158.2, 158.9. MS (ESI): m/z = 525.4 [M + Na+]. IR: 3409, 3272, 2955, 2856, 1722, 1268, 1097, 833, 777, 696 cm-¹. Anal. Calcd for C26H38N2O6Si: C, 62.12; H, 7.62; N, 5.57. Found: C, 62.06; H, 7.55; N, 5.48. [α]D ²5 -25 (c = 1, CH2Cl2) for (S,R)-2; [α]D ²5 +24 (c = 1, CH2Cl2) for (R,S)-2.
Compound 3: ¹H NMR (300 MHz, CDCl3): δ = (-0.01)-0.05 (m, 6 H), 0.81-0.82 (m, 9 H), 1.08-1.18 (m, 3 H), 3.48-4.04 (m, 4 H), 4.20-4.38 (m, 1 H), 5.14-5.30 (m, 4 H), 6.69-6.74 (m, 1 H), 7.32-7.37 (m, 10 H). ¹³C NMR (75 MHz, CDCl3): δ = -5.3, -5.2, -4.3, -4.2, 17.6, 21.2, 21.3, 25.5, 25.6, 59.7, 59.8, 64.1, 65.8, 68.1, 68.2, 68.5, 68.7, 127.6, 128.0, 128.1, 128.2, 128.4, 128.5, 135.2, 135.5, 135.8, 156.3, 156.9, 157.6, 158.2. MS (ESI): m/z = 525.4 [M + Na+]. IR: 3401, 3270, 2953, 2855, 1721, 1256, 1072, 836, 776, 696 cm-¹. Anal. Calcd for C26H38N2O6Si: C, 62.12; H, 7.62; N, 5.57. Found: C, 62.02; H, 7.35; N, 5.55. [α]D ²5 -3 (c = 1, CH2Cl2) for (R,R)-3; [α]D ²5 +3 (c = 1, CH2Cl2) for (S,S)-3.