O-(1-Phenylbutyl)benzyloxyacetaldoxime, a Versatile Reagent for the Asymmetric Synthesis of Protected 1,2-Aminoalcohols and 2-Hydroxymethyl Nitrogen Heterocycles

Abstract

Addition of organometallic reagents to O-(1-phenylbutyl)benzyloxyacetaldoxime in the presence of boron trifluoride diethyl etherate is highly diastereoselective; the resulting hydroxylamines are readily converted into protected 1,2-aminoalcohols and 2-hydroxymethyl nitrogen heterocycles, including the iminosugar 1,4-dideoxy-1,4-imino-d-ribitol, in high enantiomeric excess.

asymmetric synthesis - organometallic reagents - oximes - amino alcohols - piperidines

References

1

Deceased 30 August 2002.

2 For a recent example, see: Tang TP. Volkman SK. Ellman JA. J. Org. Chem.  2001,  66:  8772 

3 Bloch R. Chem. Rev.  1998,  98:  1407 

4 Merino P. Franco S. Merchan FL. Tejero T. Synlett  2000,  442 

5 Adams JP. J. Chem. Soc., Perkin Trans. 1  2000,  125 

6 Hunt JCA. Lloyd C. Moody CJ. Slawin AMZ. Takle AK. J. Chem. Soc., Perkin Trans. 1  1999,  3443 

7 Moody CJ. Gallagher PT. Lightfoot AP. Slawin AMZ. J. Org. Chem.  1999,  64:  4419 

8 Gallagher PT. Hunt JCA. Lightfoot AP. Moody CJ. J. Chem. Soc., Perkin Trans. 1  1997,  2633 

9

(E)-(S)-(-)-O-(1-Phenylbutyl)benzyloxyacetaldoxime [(S)-1]; colourless oil; [α] _d ²⁴ -6.7 (c 0.90, CHCl₃); δ_H (300 MHz; CDCl₃) 7.54 (1 H, t, J = 6.8 Hz, N=CH), 7.31 (10 H, m, ArH), 5.09 (1 H, t, J = 7.0 Hz, OCH), 4.44 (2 H, AB, J = 12.5 Hz, CH ₂Ph), 4.07 (2 H, m, CH ₂CHN), 1.95 (1 H, m, CHH), 1.73 (1 H, m, CHH), 1.51-1.26 (2 H, m, CH ₂Me), 0.95 (3 H, t, J = 7.3 Hz, Me); δ_C (75 MHz; CDCl₃) 147.5 (N=CH), 142.8 (C), 137.9 (C), 128.8 (CH), 128.7 (CH), 128.4 (CH), 128.2 (CH), 127.8 (CH), 127.1 (CH), 85.6 (OCH), 72.7 (CH₂), 67.1 (CH₂), 38.7 (CH₂), 19.3 (CH₂), 14.4 (Me).

10

General procedure. The oxime ether 1 (3.9 mmol, 1 equiv) was dissolved in toluene (10 mL) under nitrogen and cooled to -78 °C or -90 °C. Boron trifluoride etherate (11.8 mmol, 3 equiv) was added and the mixture stirred for 15 min. The organometallic reagent (11.8 mmol, 3 equiv) was added dropwise over 30 min at this temperature, and the mixture stirred until all starting material was consumed. The reaction mixture was quenched at this temperature with aq sat. ammonium chloride solution (10 mL), and allowed to warm to r.t. The mixture was extracted with ether (3 × 15 mL), combined, dried (K₂CO₃), filtered and evaporated. The residue was purified by column chromatography on silica gel.

11

(R)-N-tert-Butoxycarbonyl-1-hydroxy-2-propylamine (N-Boc-alaninol)(4a); mp 49-50 °C (lit., [12] mp 52-53 °C); [α] _d ¹⁹ +8.6 (c 0.8, CHCl₃) {lit., [12] [α] _d ²⁶ +10.0 (c 1.0, MeOH)}; (S)-N-tert-butoxycarbonyl-1-hydroxy-3-phenyl-2-propylamine (N-Boc-phenylalaninol)(4c); mp 89-91 °C (lit., [13] mp
91-92 °C); [α] _d ¹⁷ -32.4 (c 1.0, CHCl₃) {lit., [12] [α] _d ²⁵ -25.0
(c 1.0, MeOH)}.

12 Hamada Y. Shibata M. Sugiura T. Kato S. Shioiri T. J. Org. Chem.  1987,  52:  1252 

13 Falkiewicz B. Kolodziejczyk AS. Liberek B. Wisniewski K. Tetrahedron  2001,  57:  7909 

14 For earlier related work, see: Hunt JCA. Laurent P. Moody CJ. Chem. Commun.  2000,  1771 

15 Asano N. Oseki K. Tomioka E. Kizu H. Matsui K. Carbohydr. Res.  1994,  259:  243 

16 Kumareswaran R. Hassner A. Tetrahedron: Asymmetry  2001,  12:  3409 

17

1,4-Dideoxy-1,4-imino-d-ribitol hydrochloride salt 8; mp 124-125 °C (lit., [15] mp 130-132 °C); [α] _d ²⁵ +53.3 (c 0.75, H₂O) {lit., [15] [α] _d ²⁰+53.9 (c 1.0, H₂O)}.