The First I₂-Promoted Efficient Aminoacetylation of Activated Aziridines in Ionic Liquid

Abstract

A novel and efficient aminoacetylation of aziridines is reported. Herein, 2-phenyl-1,3-oxazolan-5-one with tosylaziridines affords 3-(N-substituted)aminopyrrolidin-2-ones via regioselective terminal aziridine opening–aminoacetylative cyclization cascades. The reaction is performed using [bmim]OH/molecular iodine as a new catalyst system where ionic liquid [bmim]OH also works as reaction media and proceeds via an isolable intermediate. After isolation of the product, the ionic liquid, [bmim]OH can be easily recycled for further use without any loss of efficiency. No byproduct formation, operational simplicity, ambient temperature, high yield, and excellent diastereoselectivity are salient features of the present synthetic protocol.

Key words

pyrrolidine-2-ones - ionic liquid - aziridines - diastereo­selectivity - molecular iodine

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• 33 General Procedure for the Synthesis of γ-Lactams 3 A mixture of 2-phenyl-1,3-oxazol-5-one (1, 2.0 mmol), tosylaziridine 2 (2.0 mmol), and a catalytic amount of I₂ (0.2 mmol) in [bmim]OH (5 mL) was stirred at r.t. for 5–6 h. After completion of the reaction as indicated by TLC, H₂O (10 mL) was added, and the mixture was extracted thrice with EtOAc (10 mL). The combined organic layer was washed with brine (10 mL), dried over anhyd Na₂SO₄, filtered, and evaporated under reduced pressure to afford an analytically pure sample of a single diastereomers 3 (Table 2). After isolation of the products, the remaining aqueous layer containing the ionic liquid was washed with hexane and dried in vacuum resulting in recycled ionic liquid, [bmim]OH (Table 3). The structure of the product 3 was confirmed by their elemental and spectral analyses. Characterization Data of Representative Compounds 3 Compound 3a: colorless solid, mp 103–104 °C. IR (KBr): ν_max = 3348, 3031, 2938, 1746, 1701, 1605, 1583, 1451 cm^–1. ¹H NMR (400 MHz, ₃): d = 2.31 (s, 3 H), 2.81 (ddd, J = 10.8, 7.1, 4.3 Hz, 1 H), 2.90 (ddd, J = 10.8, 8.9, 6.5 Hz, 1 H), 4.61 (ddd, J = 8.9, 7.5, 4.3 Hz, 1 H), 4.89 (dd, J = 7.1, 6.5 Hz, 1 H), 7.21–7.49 (m, 10 H), 7.85–7.98 (m, 4 H), 8.12 (br, exch, 1 H). ¹³C NMR (100 MHz ₃): d = 25.1, 33.7, 43.3, 53.5, 127.1, 127.9, 128.6, 129.3, 130.0, 130.7, 132.5, 133.2, 133.8, 134.7, 139.2, 140.1, 171.0, 178.3. MS (EI): m/z = 434 [M⁺]. Anal. Calcd for C₂₄H₂₂N₂O₄S: C, 66.34; H, 5.10; N, 6.45. Found: C, 66.59; H, 5.31; N, 6.27 Compound 3e: colorless solid, mp 151–153 °C. IR (KBr): ν_max = 3355, 3032, 2925, 1741, 1701, 1596, 1577, 1451 cm^–1. ¹H NMR (400 MHz, CDCl₃): d = 2.28 (s, 3 H), 2.78 (ddd, J = 10.7, 7.4, 4.8 Hz, 1 H), 2.90 (ddd, J = 10.7, 9.0, 6.6 Hz, 1 H), 4.63 (ddd, J = 9.0, 7.5, 4.8 Hz, 1 H), 4.85 (dd, J = 7.4, 6.6 Hz, 1 H), 7.26–7.53 (m, 9 H), 7.88–7.91 (m, 4 H), 8.15 (br, exch, 1 H). ¹³C NMR (100 MHz, CDCl₃): d = 25.5, 33.2, 43.8, 54.0, 127.2, 127.9, 128.7, 129.5, 130.1, 130.8, 131.4, 132.0, 132.7, 133.3, 134.0, 138.9, 171.2, 178.2. MS (EI): m/z = 468, 470 [M⁺, M⁺ + 2]. Anal. Calcd for C₂₄H₂₁ClN₂O₄S: C, 61.47; H, 4.51; N, 5.97. Found: C, 61.69; H, 4.13; N, 6.19. Compound 3i: colorless solid, mp 135–137 °C. IR (KBr): ν_max = 3350, 3029, 2932, 1743, 1702, 1601, 1578, 1445 cm^–1. ¹H NMR (400 MHz, CDCl₃): d = 2.28 (s, 3 H), 2.82 (ddd, J = 10.9, 7.1, 4.3 Hz, 1 H), 2.92 (ddd, J = 10.9, 8.9, 6.7 Hz, 1 H), 4.66 (ddd, J = 8.9, 7.5, 4.3 Hz, 1 H), 4.86 (dd, J = 7.1, 6.7 Hz, 1 H), 7.19–7.55 (m, 9 H), 7.79–7.92 (m, 4 H), 8.17 (br, exch, 1 H). ¹³C NMR (100 MHz, CDCl₃): d = 25.6, 33.1, 43.5, 53.5, 127.7, 128.4, 129.0, 129.6, 130.3, 131.1, 131.8, 132.5, 133.2, 134.0, 134.8, 140.1, 171.0, 178.8. MS (EI): m/z = 452 [M⁺]. Anal. Calcd for C₂₄H₂₁FN₂O₄S: C, 63.70; H, 4.68; N, 6.19. Found: C, 63.89; H, 4.91; N, 5.87.
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• 35 Isolation of 4a (Ar = Ph), 4e (Ar = 4-ClC₆H₄), and 4i (Ar = 4-FC₆H₄) and Their Conversion into the Corresponding Pyrrolidin-2-ones 3a, 3e, and 3i The procedure followed was the same as described above for the synthesis of 3, except that the reaction time in this case was only 2 h instead of 5–6 h used for 3. To obtain analytically pure samples of 3a, 3e, and 3i and to assign stereochemistry the same procedure was adopted as described for 3a, 3e, and 3i. Finally, these intermediates were stirred at r.t. for the next 3–4 h to give the corresponding cyclized products 3a, 3e, and 3i respectively. Characterization Data of Representative Compound Compound 4a: IR (KBr): ν_max = 3345, 3030, 2930, 1708, 1605, 1581, 1455 cm^–1. ¹H NMR (400 MHz, ₃): d = 2.23 (s, 3 H), 2.51–2.53 (m, 2 H), 3.81 (m, 1 H), 4.01 (dd, J = 7.9, 3.8 Hz, 1 H), 5.29 (br, exch, 1 H), 7.21–7.59 (m, 12 H), 7.85–7.81 (m, 2 H). ¹³C NMR (100 MHz, ₃): d = 25.1, 37.2, 45.5, 64.2, 126.7, 127.5, 128.2, 129.0, 129.7, 130.3, 132.0, 132.6, 133.3, 134.0, 135.2, 138.5, 169.8, 177.2. MS (EI): m/z = 434 [M⁺]. Anal. Calcd for C₂₄H₂₂N₂O₄S: C, 66.34; H, 5.10; N, 6.45. Found: C, 66.63; H, 4.88; N, 6.19.
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