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Synlett 2006(19): 3255-3258  
DOI: 10.1055/s-2006-951545
LETTER
© Georg Thieme Verlag Stuttgart · New York

New N-Substituted Dipolarophiles in 1,3-Dipolar Cycloaddition of Nitrones

Thanh Binh Nguyena, Catherine Gaulona, Teddy Chapina, Sébastien Tardyb, Arnaud Tatibouëtb, Patrick Rollinb, Robert Dhala, Arnaud Martela, Gilles Dujardin*a
a UCO2M UMR 6011 CNRS, Université du Maine, 72085 Le Mans, France
Fax: +33(2)43833344; e-Mail: gilles.dujardin@univ-lemans.fr;
b ICOA UMR 6005 CNRS, Université d’Orléans, 45067 Orléans, France
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Publication History

Received 24 July 2006
Publication Date:
23 November 2006 (online)

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Abstract

(N-Vinyl)-1,3-oxazolidin-2-ones, -1,3-oxazolidine-2-thi-ones and -N′-methylimidazolidin-2-one were conveniently used as new dipolarophiles in thermal 1,3-dipolar cycloaddition involving activated nitrones, and led to new 5-N-substituted isoxazolidines in high yields. A moderate to total trans-diastereoselectivity was observed, increasing with the degree of substitution at C-4.

Key words

1,3-dipolar cycloaddition - dipolarophile - nitrone - N-vinyl-oxazolidinone - oxazolidinethione - imidazolidinone

    References and Notes

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7

Optimized Experimental Procedure for Thermal 1,3-DC.
A stirred toluene solution (5 mL) of dipolarophile (0.5 mmol, 1 equiv) and nitrone (0.5 mmol, 1 equiv) was refluxed under argon. After cooling, the crude mixture was concentrated in vacuo. The product was purified by column chromatography on silica gel.
Physical data of selected isolated adducts.
Compound cis-3: pale yellow oil. IR (neat): 1738, 1194, 1028 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.25 (t, 3 H, J = 7.1 Hz, Et), 2.57 (ddd, 1 H, J = 4.1, 7.6, 13.6 Hz, H-4A), 2.87 (ddd, 1 H, J = 8.2, 9.1, 13.6 Hz, H-4B), 3.55 (dd, 1 H, J = 7.6, 9.1 Hz, H-4′), 3.75 (dt, 1 H, J 4 = 5.9, 9.1 Hz, H-4′), 3.84 (q, 1 H, J = 9.1 Hz), 4.00 (dd, 1 H, J = 13.5 Hz), 4.12 (m, 3 H), 4.29 (m, 2 H, H-5′), 5.92 (dd, 1 H, 3 J 5-4A = 4.1 Hz, 3 J 5-4B = 8.2 Hz, H-5), 7.28-7.37 (m, 5 H, H-Ar). 13C NMR (100 MHz, CDCl3): δ = 13.9 (Et), 36.3 (C-4), 40.8 (C-4′), 61.5, 61.6 (Bn, OEt), 62.3 (C-5′), 66.6 (C-3), 81.5 (C-5), 127.6, 128.2, 129.1, 135.8 (C-Ar), 157.6 (C-2′), 169.8 (C=O).
Compound trans-3: pale yellow oil. IR (neat): 1737, 1182, 1034 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.28 (t, 3 H, 3 J 8-7 = 7.1 Hz, Et), 2.55 (ddd, 1 H, 3 J 4A-5 = 4.4 Hz, 3 J 4A-3 = 7.9 Hz, 2 J 4A-4B = 13.3 Hz, H-4A), 2.83 (ddd, 1 H, 3 J 4B-5 = 6.9 Hz, 3 J 4B-3 = 7.9 Hz, 2 J 4B-4A = 13.3 Hz, H-4B), 3.54 (t, 2 H, 3 J 4 ′ -5 ′ = 7.9 Hz, H4 ′), 3.74 (m, 1 H, H-3), 4.11 (m, 2 H, Bn), 4.18 (q, 2 H, 3 J 7-8 = 7.1 Hz, OEt), 4.30 (t, 2 H, 3 J 4 ′ -5 ′ = 7.3 Hz, H5 ′), 5.84 (dd, 1 H, 3 J 5-4A = 4.4 Hz, 3 J 5-4B = 7.9 Hz, H-5), 7.27-7.38 (m, 5 H, H-Ar). 13C NMR (100 MHz, CDCl3): δ = 14.1 (Et), 35.4 (C-4), 40.4 (C-4′), 60.3 (Bn), 61.5 (OEt), 62.1 (C-5′), 65.3 (C-3), 82.1 (C-5), 127.7, 128.3, 129.3, 135.8 (C-Ar), 157.2 (C-2′), 169.3 (C=O). HRMS (EI): m/z calcd for C16H20N2O5 [M]+: 320.1372; found: 320.1393.
Compound cis-8: colorless crystals; mp 185-186 °C. IR (neat): 1743, 1410, 1234, 1018 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.40 (ddd, 1 H, 3 J 4A-5 = 5.3 Hz, 3 J 4A-3 = 6.3 Hz, 2 J 4A-4B = 13.4 Hz, H-4A), 3.04 (dt, 1 H, 3 J 4B-3 = 3 J 4B-5 = 8.3 Hz, 2 J 4B-4A = 13.4 Hz, H-4B), 3.37 (dt, 1 H, 3 J 4 ′ B-5 ′ A = 5.3 Hz, 2 J 4 ′ B-4 ′ A = 3 J 4 ′ B-5 ′ B = 8.3 Hz, H-4′B), 3.68 (q, 1 H, 3 J 4 ′ A-5 ′ = 2 J 4 ′ A-4 ′ B = 8.3 Hz, H-4′A), 4.26 (dt, 1 H, 3 J 5 ′ B-4 ′ = 8.3 Hz, 2 J 5 ′ B-5 ′ A = 9.1 Hz, H-5′B), 4.34 (ddd, 1 H, 3 J 5 ′ A-4 ′ B = 5.3 Hz, 3 J 5 ′ A-4 ′ A = 8.3 Hz, 2 J 5 ′ A-5 ′ B = 9.1 Hz, H-5′A), 4.72 (dd, 1 H, 3 J 3-4A = 6.3 Hz, 3 J 3-4B = 8.3 Hz, H-3), 6.13 (dd, 1 H, 3 J 5-4A = 5.3 Hz, 3 J 5-4B = 8.3 Hz, H-5), 7.00 (t, 1 H, J = 7.5 Hz), 7.03 (d, 2 H, J = 7.5 Hz,), 7.24 (t, 2 H, J = 7.5 Hz,), 7.31 (t, 1 H, J = 7.5 Hz), 7.39 (t, 1 H, J = 7.5 Hz), 7.51 (d, 1 H, J = 7.5 Hz,). 13C NMR (100 MHz, CDCl3): δ = 40.2 (C-4′), 41.2 (C-4), 62.3 (C-5′), 70.0 (C-3), 82.4 (C-5), 116.3, 123.2, 126.4, 127.8, 128.9, 129.0, 140.6, 150.2 (C-Ar), 157.8 (C-2′). Anal. Calcd for C18H18N2O3: C, 69.66; H, 5.85; N, 9.03. Found: C, 69.64; H, 5.74; N, 9.18.
Compound trans-15: pale yellow oil. IR (neat): 1731, 1489, 1477, 1324, 1260, 1186 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.32 (t, 3 H, 3 J 8-7 = 7.1 Hz, Et), 2.45 (ddd, 1 H, 3 J 4A-5 = 3.5 Hz, 3 J 4A-3 = 8.1 Hz, 2 J 4A-4B = 13.9 Hz, H-4A), 3.02 (ddd, 1 H, 3 J 4B-5 = 8.1 Hz, 3 J 4B-3 = 9.1 Hz, 2 J 4B-4A = 13.9 Hz, H-4B), 3.59-3.71 (m, 2 H, H-4′), 3.84 (br, 1 H, H3), 4.12 (s, 2 H, Bn), 4.23 (q, 2 H, 3 J 7-8 = 7.1 Hz, OEt), 4.41-4.51 (m, 2 H, H-5′), 6.39 (dd, 1 H, 3 J 5-4A = 3.5 Hz, 3 J 5-4B = 8.1 Hz, H-5), 7.28-7.35 (m, 5 H, H-Ar). 13C NMR (100 MHz, CDCl3): δ = 14.3 (Et), 36.7 (C-4), 43.4 (C-4′), 59.2 (Bn), 61.5 (OEt), 64.8 (C-3), 67.0 (C-5′), 84.7 (C-5), 127.8, 128.4, 129.3, 135.9 (C-Ar), 169.1 (C=O), 187.6 (C-2′). HRMS (ESI+): m/z calcd for C16H20N2O4SK [M + K]+: 375.0781; found: 375.0775.
Compound trans-19: pale yellow oil. IR (neat): 1734, 1474, 1353, 1283, 1208 cm-1. 1H NMR (400 MHz, CDCl2CDCl2, 60 °C): δ = 1.20 (t, 3 H, 3 J 7-8 = 7.1 Hz, Et), 1.22 (s, 3 H, Me), 1.30 (s, 3 H, Me), 2.80 (ddd, 1 H, 3 J 4A-5 = 6.0 Hz, 3 J 4A-3 = 8.6 Hz, 2 J 4A-4B = 13.9 Hz, H-4A), 3.08 (ddd, 1 H, 3 J 4B-3 = 6.3 Hz, 3 J 4B-5 = 7.6 Hz, 2 J 4B-4A = 13.9 Hz, H-4B), 3.97 (dd, 1 H, 3 J 3-4A = 8.6 Hz, 3 J 3-4B = 6.3 Hz, H-3), 4.01 (s, 2 H, Bn), 4.06-4.12 (m, 4 H, OEt and H-5′), 5.74 (dd, 1 H, 3 J 5-4A = 6.0 Hz, 3 J 5-4B = 7.6 Hz, H-5), 7.16-7.29 (m, 5 H, H-Ar). 13C NMR (100 MHz, CDCl2CDCl2, 60 °C): δ = 14.2 (Et), 25.4 (Me), 25.8 (Me), 37.1 (C-4), 60.4 (Bn), 61.3 (OEt), 64.2 (C-4′), 66.0 (C-3), 79.3 (C-5′), 84.6 (C-5), 127.5, 128.2, 129.5, 136.4 (C-Ar), 169.6 (C=O), 186.4 (C-2′).

11

Complete complexation was ascertained by 1H NMR.

14

Under our standard conditions, similar levels of trans-selectivity were observed in the reaction of 1 with ethyl vinyl ether (4:1) and tert-butyl vinyl ether (3:1).