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Synlett 2008(20): 3149-3152  
DOI: 10.1055/s-0028-1087367
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Highly Enantioselective Aziridination of N-Protected Imines: Comparison of the Phosphazene EtP2 and Sodium Hydride as Bases

Irena Stipetić, Marin Roje, Zdenko Hameršak*
Department of Organic Chemistry and Biochemistry, Rudjer Bošković Institute, P. O. Box 180, 10002 Zagreb, Croatia
Fax: +385(1)4680108; e-Mail: hamer@irb.hr;
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Publikationsverlauf

Received 4 September 2008
Publikationsdatum:
26. November 2008 (online)

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Abstract

Asymmetric synthesis of 2,3-disubstituted N-Boc, N-SES, and N-Ts aziridines starting from N-protected imines, using sulfonium salt derived from Eliel’s oxathiane, is reported. Sodium hydride was successfully used as a substitute for the phosphazene base EtP2 without any loss of yield, enantioselectivity, or diastereoselectivity.

Key words

asymmetric synthesis - aziridines - enantioselectivity - imine - ylide

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14

N -(1-Naphthylidene)-2-trimethylsilylethanesulfon-amide (15)
A mixture of 1-naphthaldehyde (300 mg, 0.26 mL, 1.91 mmol, 1 equiv), 2-(trimethylsilyl)ethanesulfonamide (415 mg, 2.29 mmol, 1.2 equiv), and anhyd Et3N (1.26 mL, 9.1 mmol, 4 equiv) in anhyd CH2Cl2 (15 mL), under argon, was cooled to 0 ˚C. A TiCl4 solution in CH2Cl2 (1.9 mL of 1 M solution, 1 equiv) was carefully added, and reaction mixture was stirred at 0 ˚C for 1 h, and then at r.t. for 20 h. The reaction mixture was filtered trough Celite, concentrated, and toluene (20 mL) was added to the solid residue. After 10 min of stirring, the mixture was filtered, and the filtrate concentrated under vacuum. The NMR analysis of the crude product 15 showed that it containes 4% of the starting amide and 96% of the imine. The product was found to decompose on silica gel and was used in the next step without further purification (570 mg, w = 98%, yield 89%). ¹H NMR (300 MHz, CDCl3): δ = 0.07 (s, 9 H), 1.09-1.15 (m, 2 H), 3.19-3.25 (m, 2 H), 7.59-7.65 (m, 2 H), 7.71 (td, 1 H, J 1 = 7.7 Hz, J 2 = 1.4 Hz), 7.96 (d, 1 H, J = 8.0 Hz), 8.15 (d, 1 H, J = 8.0 Hz), 8.19 (d, 1 H, J = 7.2 Hz), 9.04 (d, 1 H, J = 8.0 Hz), 9.59 (s, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = -2.09, 9.50, 49.01, 124.22, 125.08, 126.95, 127.48, 128.91, 129.03, 131.73, 133.76, 135.22, 136.14, 170.91.

15

2-Phenyl-3-(1-naphthyl)-1-(2-trimethylsilylethane-sulfonyl)-aziridine (21)
To a stirred solution of benzyl sulfonium salt 1 (352 mg, 0.80 mmol, 1 equiv) under argon in anhyd THF (10 mL), cooled to -40 ˚C, NaH dispersion in paraffin (64 mg, w = 60%, 1.6 mmol, 2 equiv) was added. After 1 h, a THF solution (2 mL) of N-(1-naphthylidene)-2-trimethylsilylethanesulfonamide (15, 270 mg, w = 98%, 0.80 mmol, 1 equiv) was dropwise added. The reaction mixture was stirred for 20 h at -40 ˚C. Cold H2O (15 mL) was carefully added, and the mixture was extracted with CH2Cl2 (3 × 10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under vacuum. The crude product was analyzed by ¹H NMR to determine the diastereomeric ratio and then was purified by column chromatography on silica gel. First fraction contained recovered (R,R,R)-oxathiane 2 (145 mg, 90%);
R f = 0.8 (PE-EtOAc, 8:2).The title compound 21 was isolated as colorless oil (201 mg, 63%); R f = 0.47 (PE-EtOAc, 8:2). Isomers of 21 were separated by chiral HPLC; trans: ee >99% [Chiralcel OD, hexane-EtOAc (90:10), 254 nm, 1 mL/min, t R(minor) = 11.5 min, t R(major) = 14.4 min]; [α]D ²5 +75 (c 1; CH2Cl2). ¹H NMR (300 MHz, CDCl3): δ = -0.05 (s, 9 H), 1.05-1.09 (m, 2 H), 2.94-3.06 (m, 2 H), 4.32 (d, 1 H, J = 4.5 Hz), 4.80 (d, 1 H, J = 4.5 Hz), 7.40-7.56 (m, 5 H), 7.60 (td, 1 H, J 1 = 7.7 Hz, J 2 = 1.1 Hz), 7.64 (d, 2 H, J = 8.1 Hz), 7.68 (d, 1 H, J = 7.1 Hz), 7.88 (d, 1 H, J = 8.1 Hz), 7.91 (d, 1 H, J = 8.1 Hz), 8.25 (d, 1 H, J = 8.1 Hz). ¹³C NMR (75 MHz, CDCl3): δ = -2.16, 9.63, 48.58, 49.49, 50.97, 123.55, 125.19, 125.22, 126.15, 126.70, 128.32, 128.72, 128.81, 128.93, 129.37, 129.60, 132.47, 133.28, 133.55. IR (KBr): 3057, 2950, 1325, 1250, 1145, 932, 843, 796 cm-¹. Anal. Calcd for C23H27NO2SSi (409.62): C, 67.44; H, 6.64; N, 3.42. Found: C, 67.36; H, 7.06; N, 3.50. Cis: ee >99% [Chiralcel OD, hexane-EtOH (90:10), 254 nm, 1 mL/min, t R(minor) = 5.7 min, t R(major) = 8.0 min], [α]D ²5 +197 (c 0.35, CH2Cl2). ¹H NMR (300 MHz, CDCl3): δ = 0.01 (s, 9 H), 1.23-1.29 (m, 2 H), 3.25-3.31 (m, 2 H), 4.39 (d, 1 H, J = 7.2 Hz), 4.67 (d, 1 H, J = 7.2 Hz), 7.01-7.03 (m, 3 H), 7.12-7.17 (m, 2 H), 7.32-7.53 (m, 3 H), 7.58 (d, 1 H, J = 7.1 Hz), 7.70 (d, 1 H, J = 8.1 Hz), 7.77 (d, 1 H, J = 8.1 Hz), 8.04 (d, 1 H, J = 8.1 Hz). ¹³C NMR (75 MHz, CDCl3): δ = -2.11, 9.86, 46.02, 47.27, 49.17, 122.84, 124.84, 125.80, 125.98, 126.31, 127.27, 127.71, 127.78, 127.79, 128.36, 128.50, 131.26, 131.97, 133.08. IR (KBr): 3059, 2950, 1328, 1250, 1145, 911, 841, 804 cm-¹
2-Phenyl-3-(4-methoxyphenyl)-1-( tert -butoxycarbonyl)-aziridine (23) Compound 23 was prepared as above starting from N-(tert-butoxycarbonyl)-4-methoxybenzaldimine (17, 100 mg, 0.42 mmol, 1 equiv), and was isolated as colorless oil after workup and chromatography on neutral alumina, activity I (42 mg, 31%); R f = 0.55 (hexane-EtOAc, 9:1). Product 23 is a cis/trans mixture (9:91), and the assignments are of the major trans-isomer. Trans: ee = 96% [Chiralpak AD, hexane-2-PrOH (92:8), 229 nm, 1 mL/min, t R(major) = 25.7 min, t R(minor) = 28.8 min]. ¹H NMR (300 MHz, CDCl3):
δ = 1.20 (s, 9 H), 3.71 (d, 1 H, J = 3.3 Hz), 3.76 (d, 1 H, J = 3.3 Hz), 3.81 (s, 3 H), 6.89 (d, 2 H, J = 9.1 Hz), 7.27 (d, 2 H, J = 9.1 Hz), 7.32-7.35 (m, 5 H). ¹³C NMR (75 MHz, CDCl3): δ = 27.67, 47.09, 47.73, 55.35, 81.34, 113.91, 126.93, 127.40, 127.98, 128.33, 128.47, 135.87, 159.54, 160.56. IR (KBr): 2926, 1752, 1720, 1608, 1519, 1255, 990, 831 cm-¹.
2-Phenyl-3-(1-naphthyl)-1-( tert -butoxycarbonyl)-aziridine (24)
Compound 24 was prepared as above starting from N-(tert-butoxycarbonyl)-1-naphthaldimine (18, 100 mg, 0.39 mmol, 1 equiv), and was isolated as viscous colorless oil after workup (101 mg, 75%); R f = 0.22 (hexane-EtOAc, 8:2). Even though the crude mixture contained mixture of trans/cis isomers (98:2), after chromatography, only trans-isomer was isolated. Trans: ee = 96% (Chiralcel OJ, hexane-EtOH (95:5), 254 nm, 1 mL/min, t R(minor) = 9.9 min, t R(major) = 12.5 min]. [α]D ²5 +89 (c 2.1, CH2Cl2). ¹H NMR (300 MHz, CDCl3): δ = 1.02 (s, 9 H), 3.85 (d, 1 H, J = 3.5 Hz), 4.47 (d, 1 H, J = 3.5 Hz), 7.37-7.54 (m, 8 H), 7.61 (d,
1 H, J = 6.8 Hz), 7.83 (d, 1 H, J = 8.5 Hz), 7.87-7.89 (m, 1 H), 8.22-8.25 (m, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 27.42, 44.66, 47.18, 81.32, 123.95, 124.18, 125.39, 125.63, 125.97, 126.42, 127.51, 128.33, 128.53, 128.65, 132.01, 132.55, 133.42, 135.04, 160.11. IR (KBr): 3052, 2976, 2926, 1711, 1295, 1148, 779 cm-¹. Anal. Calcd for C23H23NO2 (345.43): C, 79.97; H, 6.71; N, 4.05. Found: C, 79.90; H, 6.50; N, 3.89.