Allylation Reactions of N,O-Heterocycles

Abstract

Iminium ions generated from isoxazolidines and tetrahydro-1,2-oxazines undergo allylation under Sakurai conditions. Allylated isoxazolidines are formed predominantly as the trans isomer, while oxazines are formed exclusively as the cis isomer.

Key words

heterocycles - allylation - stereoselectivity

• References and Notes

• 1 Bates RW, Boonsombat J, Lu Y, Nemeth JA, Sa-Ei K, Song P, Cai MP, Cranwell PB, Winbush SA. Pure Appl. Chem. 2008; 80: 681

For the use of isoxazolidines for β-amino acid synthesis, see:
• 2a Fuller AA, Chen B, Minter AR, Mapp AK. Synlett 2004; 1409
• 2b Examples in sedum alkaloid synthesis may be found in: Bates RW, Sa-Ei K. Tetrahedron 2002; 58: 5957
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• 4b Bates RW, Lu Y. J. Org. Chem. 2009; 74: 9460
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• 5 For another noncycloaddition route to isoxazolidines, see: Lemen GS, Giampietro NC, Hay MB, Wolfe JP. J. Org. Chem. 2009; 74: 2533
• 6 Also, 3,4-trans is favoured: Bates RW, Lim CJ. Synlett 2010; 866
• 7 Bates RW, Snell RH, Winbush SA. Synlett 2008; 1042

For recent reviews of N-acyliminium ion chemistry, see:
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Certain 3-methoxyisoxazolidines and derivatives, prepared by 1,3-dipolar cycloaddition, have been claimed as anti-acne agents:
• 11a Castelhano AL, DeYoung LM, Krantz A, Pliura DH, Venuti MC. US 4912120 A1, 1990
• 11b Castelhano AL, Krantz A, Pliura DH, Venuti MC, DeYoung LM. EP 237082 B1, 1991
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• 13 5-Hydroxyisoxazolidines have also been prepared by the reaction between hydroxylamines and α,β-unsaturated aldehydes: Zelenin KN, Motorina IA, Sviridova LA, Bezhan IP, Ershov AY, Golubeva GA, Bundel YG. Chem. Heterocycl. Compd. 1988; 23: 1018
• 14 Acid-catalysed exchange in 3-hydroxyisoxazolidines has been reported: Motorina IA, Sviridova LA, Golubeva GA, Zelenin KN, Bezhan IP, Ershov AY, Bundel YG. Chem. Heterocycl. Compd. 1989; 24: 1373
• 15 Details have been deposited with the Cambridge Crystallographic Data Centre and may be obtained at http://www.ccdc.cam.ac.uk. CCDC deposition numbers: 7b: 878055 and 9: 877996
• 16 Characterisation Data for Compound 7b Mp 69–71 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.25–7.50 (10 H, m), 5.35 (1 H, br), 5.33 (br d J = 12.0 Hz), 5.19 (d, J = 12.0 Hz), 4.72 (br s, 1 H), 3.35 (3 H, br s), 2.35 (1 H, app dq, J = 5.0, 12.0 Hz), 2.05–2.10 (1 H, m), 1.88–2.00 (1 H, m), 1.79–1.84 (1 H, m), 1.80–2.40 (4 H, m)
• 17 Spectroscopic Data for Compound trans-8a ¹H NMR (400 MHz, CDCl₃): δ = 7.37–7.28 (5 H, m), 5.85 (1 H, ddt, J = 17.3, 10.2, 7.1 Hz), 5.27 (1 H, t, J = 6.6 Hz), 5.21–5.14 (2 H, m), 4.39 (1 H, tt, J = 8.0, 5.0 Hz); 3.68 (3 H, s), 2.65–2.38 (4 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 157.5, 138.5, 134.0, 128.8, 118.4, 81.7, 59.0, 53.2, 40.0, 39.1
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• 18b Mulvihill MJ, Gage JL, Miller MJ. J. Org. Chem. 1998; 63: 3357
• 19 Spectroscopic Data for Compound 10c ¹H NMR (400 MHz, CDCl₃): δ = 5.67–5.78 (m, 1 H), 5.15 (1 H, ddd, J = 17.0, 3.0, 1.5 Hz), 5.08 (1 H, dt, J = 10.0, 1.0 Hz), 4.73 (1 H, br d), 4.35 (1 H, br), 3.78 (3 H, s), 2.70 (1 H, app quin, J = 7.0 Hz), 2.44 (1 H, app quin, J = 7.0 Hz), 2.10–2.20 (1 H, m), 1.9.0–2.05 (1 H, m), 1.8.0–1.90 (2 H, m). ¹³C NMR (400 MHz, CDCl₃): δ = 25.6, 26.6, 34.3, 53.2, 83.3 (br), 117.6, 126.6, 128.5, 128.6, 134.8, 139.4, 156.1
• 20 Stereoelectronic Effects in Organic Chemistry . Deslongchamps P. Pergamon Press; Oxford: 1983: 211-221
• 21 All compounds used in this study were racemic