Lewis Acid Induced Highly Regioselective Synthesis of a New Class of Substituted Isoxazolidines

Abstract

The 1,4-addition of N,O-bis(trimethylsilyl)hydroxyl­amine to alkylidene acetoacetates afforded in one step 3,4,5-trisubstituted isoxazolidines. An investigation on the effect of the Lewis acid catalysis on the regioselectivity of the addition is also herein reported.

Keywords

isoxazolidine - oxime - addition reactions - regioselectivity - Lewis acids

References and Notes

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  3a: Major anomer: ^¹H NMR (600 MHz, C₆D₆): δ = 0.82 (d, 3 H, J = 6.6 Hz), 0.93 (t, 3 H, J = 7.2 Hz), 0.97 (d, 3 H,
  J = 6.6 Hz), 1.51 (s, 3 H), 1.64 (m, 1 H), 2.83 (d, 1 H, J = 5.4 Hz), 3.58 (dd, 1 H, J = 5.4, 7.2 Hz), 3.93 (m, 1 H), 3.98 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 14.1, 18.7, 19.4, 23.8, 32.6, 60.1, 61.3, 67.9, 106.5, 170.7. Minor anomer: ^¹H NMR (600 MHz, C₆D₆): δ = 0.86 (d, 3 H, J = 7.2 Hz), 0.88 (d, 3 H, J = 6.6 Hz), 0.91 (t, 3 H, J = 7.2 Hz), 1.45 (s, 3 H), 1.50 (m, 1 H), 3.03 (d, 1 H, J = 7.8 Hz), 3.88 (dd, 1 H, J = 7.2, 7.8 Hz), 3.92 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 14.2, 19.6, 20.4, 22.2, 30.1, 61.1, 62.0, 71.9, 108.4, 171.5.

• 16 Jencks WP. J. Am. Chem. Soc.  1959,  81:  475 

14

4a: ^¹H NMR (300 MHz, CDCl₃): δ = 1.20 (m, 9 H), 2.05 (s, 3 H), 2.65 (m, 1 H), 4.24 (m, 2 H), 5.87 (d, 1 H, J = 10.2 Hz). ^¹³C NMR (75 MHz, CDCl₃): δ = 10.6, 14.1, 22.4, 29.4, 61.0, 131.3, 143.9, 154.4, 167.5.

15

6a: ^¹H NMR (300 MHz, C₆D₆): δ = 0.80 (d, 3 H, J = 6.6 Hz), 0.84 (d, 3 H, J = 6.9 Hz), 0.93 (t, 3 H, J = 6.9 Hz), 1.66 (s,
3 H), 1.77 (m, 1 H), 2.40 (s, 3 H), 3.16 (d, 1 H, J = 7.2 Hz), 3.95 (m, 2 H), 5.05 (dd, 1 H, J = 6.3, 7.2 Hz). ^¹³C NMR
(75 MHz, CDCl₃): δ = 14.0, 17.6, 18.7, 25.1, 33.3, 37.6, 61.0, 61.6, 65.1, 109.8, 167.5.