Synthesis, Configurational and Conformational Studies of Six Amino Sugar Precursors Formed by [3+2]Cycloaddition of Alkylnitrile Oxides to Enone Sugars

Abstract

An easy and efficient synthesis of a novel bicyclic system (isoxazolino-pyranoside), obtained by the 1,3-dipolar cyclo­addition of acetonitrile and propionitrile oxides to highly reactive α,β-unsaturated sugar enones, is described. The configuration and conformation of these new compounds were inferred from their spectroscopic data.

tri-O-acetyl-d-glucal - Montmorillonite K-10 - NMR spectroscopy - sugar enones - heterobicyclic system

References

1 Gallos JK. Koumbis AE. Xiraphari VP. Dellios CC. Coutouli-Argyropoulou E. Tetrahedron  1999,  55:  5167 

2 Nataka M. Akazawa S. Kitamura S. Tatsuta K. Tetrahedron Lett.  1991,  32:  5363 

3a Kobayashi Y. Miyazaki H. Shioazaki M. J. Am. Chem. Soc.  1992,  114:  10065 

3b Kobayashi Y. Miyazaki H. Shioazaki M. J. Org. Chem.  1994,  59:  813 

4 Gallos JK. Koftis TV. J. Chem. Soc., Perkin Trans. 1  2001,  415 

5 Srivastava RM. De Souza AMA. Da Silva LP. De Freitas Filho JR. Hallwass F. Doboszewski B. J. Braz. Chem. Soc.  2002,  13:  158 

6 De Freitas Filho JR. Srivastava RM. Soro Y. Cottier L. Descotes G. J. Carbohydr. Chem.  2001,  20:  561 

7 Toshima K. Ishizuka T. Matsuo G. Nataka M. Synlett  1995,  306 

8 Fraser-Reid B. Mclean A. Usherwood EW. Yunker M. Can. J. Chem.  1970,  48:  2877 ; and references cited therein

9 Corey EJ. Venkateswarlu A. J. Am. Chem. Soc.  1972,  94:  6190 

10 Mukaiyama T. Hoshino T. J. Am. Chem. Soc.  1960,  82:  5339 

11 Srivastava RM. Clapp LB. J. Heterocycl. Chem.  1968,  5:  61 

12 Hassner A. Dahren W. J. Org. Chem.  1990,  55:  5505 

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Representative Procedure: To a solution of enone 6a-c (1.08 mmol) in cyclohexane (10 mL) was added nitro-ethane or nitropropane (1.18 mmol), triethylamine (0.12 mmol) and phenyl isocyanate (3.95 mmol). The mixture was stirred and refluxed during 3 h (approximate time for enone disappearance on TLC). Then water (8 mL) was added and the resulting mixture was stirred for 1 h at 20 °C. After extraction of the product 7d-i with petroleum ether (2 × 15 mL), drying on Na₂SO₄, evaporating the solvent under vacuum, the raw product was purified on silica gel (eluting with 90/10% petroleum ether/EtOAc) to afford pure 7d-i. Spectra ¹H NMR (300 MHz, CDCl₃) of compounds 7d-i: Compound 7d: δ = 4.98 (s, H-1), 4.64 (d, J = 11.2 Hz, H-2), 3.95 (m, H-5, H-6), 3.90 (d, J = 11.2 Hz, H-3), 3.79 (dd, J = 2.4 Hz and 11.3 Hz, H-6′), 3.52 (m, OCH₂), 1.84 (s, CH₃), 1.15 (t, CH₃), 0.83 [s, (CH₃)₃CSi], 0.03 (s, CH₃Si). Compound 7e: δ = 4.99 (s, H-1), 4.64 (d, J = 11.3 Hz, H-2), 4.03 (m, H-5, H-6), 3.94 (d, J = 11.3 Hz, H-3), 3.70 (dd, J = 2.4 Hz and 10.5 Hz, H-6′), 3.60-3.55 (m, OCH₂), 2.34 and 2.10 (m, CH₂), 1.22-1.19 (m, CH₃), 0.82 [s, (CH₃)₃CSi], 0.04 (s, CH₃Si). Compound 7f: δ = 5.02 (s, H-1), 4.58 (d, J = 11.3 Hz, H-2), 4.20 (m, OCH), 3.97 (m, H-5, H-6), 3.88 (d, J = 11.3 Hz, H-3), 3.78 (dd, J = 2.7 Hz and 10.7 Hz, H-6′), 1.84 (s, CH₃), 1.60-1.45 (m, CH₂), 0.82 [s, (CH₃)₃CSi], 0.01 (s, CH₃Si). Compound 7g: δ = 5.03 (s, H-1), 4.58 (d, J = 11.2 Hz, H-2), 4.21 (m, OCH), 3.98 (d, J = 11.3 Hz, H-3), 3.94 (m, H-5, H-6), 3.78 (dd, J = 2.61 and 10.9 Hz, H-6′), 2.34 and 2.10 (m, CH₂C=N), 1.71-1.48 (m, CH₂), 1.16 (t, J = 7.5 Hz, CH₃), 0.81 [s, (CH₃)₃CSi], 0.09 (s, CH₃Si). Compound 7h: δ = 5.18 (s, H-1), 4.62 (d, J = 11.3 Hz, H-2), 4.03 (t, H-5), 3.91 (m, H-3, H-6), 3.78 (dd, J = 10.9 Hz and 2.8 Hz,
H-6′), 3.57 (m, OCH), 1.84 (s, CH₃), 1.74-1.19 (m, CH₂), 0.81 [s, (CH₃)₃CSi], 0.01 (s, CH₃Si). Compound 7i: δ = 5.14 (s, H-1), 4.58 (d, J = 11.3 Hz, H-2), 3.99 (d, J = 11.3 Hz,
H-3), 3.97 (m, H-5, H-6), 3.77 (dd, J = 2.8 Hz and 10.9 Hz, H-6′), 3.59 (m, OCH), 2.33 and 2.12 (m, CH₂C=N), 1.87-1.47 (m, CH₂), 1.12 (t, J = 6.1 Hz, CH₃), 0.81 [s, (CH₃)₃CSi], 0.04 (s, CH₃Si).

14 Srivastava RM. Carthy BJ. Fraser-Reid B. Tetrahedron Lett.  1974,  2175 

15

The elemental analyses of all new compounds, viz. 5a-c, 6a-c and 7d-i agreed with the proposed structures.