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Synlett 2009(19): 3123-3126  
DOI: 10.1055/s-0029-1218342
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Organocatalytic Stereoselective Aziridination of Imines via Ammonium Ylides

Lal Dhar S. Yadav*, Ritu Kapoor, Garima
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India
Fax: +91(532)2460533; e-Mail: ldsyadav@hotmail.com;
Further Information

Publication History

Received 5 September 2009
Publication Date:
05 November 2009 (online)

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Abstract

Tertiary amine catalyzed reaction of imines with phen­acyl bromide derivatives expeditiously affords functionalized aziridines in high yields and stereoselectivities in a one-pot process. Advantageously, the protocol precludes the preparation and isolation of ylides and their precursors in a separate step as they are formed in situ.

Key words

aziridines - imines - nitrogen heterocycles - organocatalysis - stereoselective reaction - ylides

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12

General Procedure for the One-Pot Synthesis of Aziridines 3: A mixture of phenacyl bromide 2 (1 mmol), DABCO (0.2 mmol), imine 1 (1 mmol), and Na2CO3 (1.5 mmol) in MeCN (5 mL) was stirred at 80 ˚C for 19-24 h (Table  [²] ). After completion of the reaction (monitored by TLC), it was quenched with aq HCl (1 M) and extracted with EtOAc (3 × 10 mL). The combined organic phases were washed with a sat. aq solution of NaHCO3, dried over MgSO4, and concentrated under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography using EtOAc-n-hexane (2:8) as eluent to afford analytically pure sample of 3 (Table  [²] ). Characterization Data of Representative Compounds:
Product 3 (Table 2, entry 2): ¹H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.6 Hz, 2 H), 7.42-7.61 (m, 3 H), 7.20-7.23 (m, 4 H), 7.10 (d, J = 8.4 Hz, 2 H), 6.75 (d, J = 8.4 Hz, 2 H), 4.51 (d, J = 4.1 Hz, 1 H), 4.28 (d, J = 4.1 Hz, 1 H), 3.72 (s, 3 H), 2.36 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 190.03, 160.30, 144.12, 136.29, 135.63, 132.63, 129.90, 129.23, 129.00, 128.61, 127.35, 127.21, 113.90, 55.60, 49.99, 47.04, 21.24. IR (KBr): 3051, 2847, 1685, 1602, 1583, 1514, 1456, 1331, 1151, 843, 741 cm-¹. EIMS: m/z = 407 [M+]. Anal. Calcd for C23H21NO4S: C, 67.79; H, 5.19; N, 3.44. Found: C, 67.99; H, 5.45; N, 3.21. Product 3 (Table 2, entry 6): ¹H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 8.5 Hz, 2 H), 7.85 (d, J = 8.9 Hz, 2 H), 7.44 (d, J = 8.9 Hz, 2 H), 7.24 (d, J = 8.5 Hz, 2 H), 7.12 (d, J = 8.3 Hz, 2 H), 6.78 (d, J = 8.3 Hz, 2 H), 4.54 (d, J = 4.1 Hz, 1 H), 4.30 (d, J = 4.1 Hz, 1 H), 3.72 (s, 3 H), 2.37 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 190.06, 160.60, 138.00, 136.66, 133.33, 130.00, 129.28, 129.10, 128.64, 127.38, 127.25, 114.20, 114.16, 55.80, 50.03, 47.09, 21.28. IR (KBr): 3049, 2842, 1687, 1603, 1584, 1516, 1448, 1336, 1146, 848 cm-¹. EIMS: m/z = 441 [M+]. Anal. Calcd for C23H20ClNO4S: C, 62.51; H, 4.56; N, 3.17. Found: C, 62.74; H, 4.29; N, 2.84. Product 3 (Table 2, entry 10): ¹H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.6 Hz, 2 H), 7.70 (d, J = 8.4 Hz, 2 H), 7.20 (d, J = 8.6 Hz, 2 H), 7.08 (d, J = 8.5 Hz, 2 H), 6.75 (d, J = 8.4 Hz, 2 H), 6.73 (d, J = 8.5 Hz, 2 H), 4.50 (d, J = 4.1 Hz, 1 H), 4.28 (d, J = 4.1 Hz, 1 H), 3.72 (s, 3 H), 3.70 (s, 3 H), 2.35 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 190.00, 162.60, 160.00, 144.08, 136.25, 130.40, 129.10, 129.00, 128.50, 127.31, 127.18, 114.30, 113.30, 55.80, 55.10, 49.95, 47.00, 21.20. IR (KBr): 3057, 2847, 1677, 1602, 1577, 1514, 1457, 1334, 1148, 842 cm-¹. EIMS: m/z = 437 [M+]. Anal. Calcd for C24H23NO5S: C, 65.89; H, 5.30; N, 3.20. Found: C, 65.62; H, 5.55; N, 2.87. Product 3 (Table 2, entry 14): ¹H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 8.8 Hz, 2 H), 8.10 (d, J = 8.8 Hz, 2 H), 8.06 (d, J = 8.5 Hz, 2 H), 7.26 (d, J = 8.5 Hz, 2 H), 7.14 (d, J = 8.2 Hz, 2 H), 6.80 (d, J = 8.2 Hz, 2 H), 4.56 (d, J = 4.1 Hz, 1 H), 4.32 (d, J = 4.1 Hz, 1 H), 3.72 (s, 3 H), 2.39 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 190.08, 170.00, 149.00, 144.19, 141.20, 136.36, 130.04, 129.90, 129.10, 127.41, 127.29, 123.00, 114.6, 56.01, 50.06, 47.12, 21.30. IR (KBr): 3064, 2853, 1683, 1603, 1584, 1512, 1453, 1338, 1150, 854 cm-¹. EIMS: m/z = 452 [M+]. Anal. Calcd for C23H20N2O6S: C, 61.05; H, 4.46; N, 6.19. Found: C, 61.37; H, 4.19; N, 6.47.

15

Chiral HPLC: enantiomeric excess (ee) was determined by using a Chiracel OD 25 cm, 4.6 mm internal diameter column, hexane-i-PrOH (88:12), flow: 1 mL min-¹, 30 ˚C,
λ = 250 nm. The enantiomers had retention times (t R) of 22.4 min (major) and 24.2 min (minor).