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Synlett 2004(3): 489-492  
DOI: 10.1055/s-2004-815444
LETTER
© Georg Thieme Verlag Stuttgart · New York

Highly Stereoselective Addition of Organomagnesium Reagents to Aziridinyl-2-carboxaldimine: Preparation of Enantiopure 2-Aminomethylaziridines and 4,5-Disubstituted Imidazolidin-2-ones

Man-Jin Suha, Sang Woo Kima,b, Seong In Beaka, Hyun-Joon Ha*a,b, Won Koo Lee*c
a Department of Chemistry, Hankuk University of Foreign Studies, Yongin, Kyunggi-Do 449-719, Korea
Fax: +82(31)3304566; e-Mail: hjha@hufs.ac.kr;
b Center for Bioactive Molecular Hybrids, Yonsei University, Seoul 120-749, Korea
c Department of Chemistry, Sogang University, Seoul 121-742, Korea
Fax: +82(2)7010967.; e-Mail: +wonkoo@sogang.ac.kr;
Further Information

Publication History

Received 3 December 2003
Publication Date:
06 February 2004 (online)

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Abstract

The addition of alkyl- and arylmagnesium reagents to chiral [1′(R)-α-methylbenzyl]aziridine-2(R)-carboxaldimines was carried out in a highly stereoselective manner to give 2-aminomethylaziridine. Further treatment of 2-aminomethylaziridines with triphosgene and NaH afforded enantiopure 5-alkyl- or 5-aryl-4-chloromethylimidazolidin-2-ones.

Key words

stereoselectivity - addition reactions - organometallic reagents - aziridines - imines

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General Procedure for the Addition Reactions of Alkyl or Aryl Magnesium Bromide: Into the solution of (p-methoxyphenyl)-{[1′(R)-α-methylbenzyl]aziridine-2(R)-ylmethylene}amine (280 mg, 1 mmol) in of Et2O (10 mL) was added ethereal solution of alkyl or aryl magnesium bromide (3 mmol) and BF3·OEt2 (0.15 mL, 0.8 mmol) under N2 atmosphere. The resultant solution was stirred at -10 °C for the reaction to be completed before being quenched by adding ice-water. The reaction product was isolated with Et2O (15 mL × 4). The ethereal solution was washed with brine twice. The organic layer was dried over anhyd MgSO4, filtered and concentrated under reduced pressure. Purification by silica gel flash column chromatography provided the analytically pure addition product. Compound 2a: colorless oil, [α]D 33.5 (c 2.0 in EtOAc). 1H NMR (200 MHz, CDCl3): δ = 1.12 (d, J = 6.0 Hz, 1 H), 1.14 (d, J = 4.2 Hz, 3 H), 1.22 (d, J = 6.2 Hz, 3 H), 1.54-1.62 (m, 2 H), 2.36 (q, J = 6.6 Hz, 1 H), 3.32-3.41 (m, 1 H), 3.63 (s, 3 H), 6.52-6.71 (m, 4 H), 7.14-7.31 (m, 5 H). 13C NMR (50.3 MHz, CDCl3): δ = 19.5, 23.5, 30.4, 44.2, 48.9, 55.6, 69.3, 114.6, 114.6, 126.6, 126.7, 128.1, 141.8, 144.6, 151.6. HRMS (EI) calcd for C19H24N2O: 296.1889. Found: 296.1883. Anal. Calcd. for C19H24N2O: C, 77.0; H, 8.16; N, 9.45. Found: C, 76.8; H, 8.09; N, 9.42. Compound 2f: colorless oil, [α]D 18.9 (c 3.0 in EtOAc). 1H NMR (200 MHz, CDCl3): δ = 1.08 (d, J = 6.8 Hz, 3 H), 1.19 (d, J = 6.2 Hz, 1 H), 1.66-1.78 (m, 2 H), 2.25 (q, J = 6.6 Hz, 1 H), 3.55 (s, 3 H), 4.04-4.08 (m, 1 H), 6.35-6.57 (m, 4 H), 7.10-7.33 (m, 10 H). 13C NMR (50.3 MHz, CDCl3): δ = 23.6, 31.5, 45.4, 55.6, 58.9, 69.1, 114.6, 114.8, 126.5, 126.7, 127.0, 127.1, 128.3, 128.5, 141.5, 142.8, 144.3, 151.7. HRMS (EI) calcd for C24H26N2O: 358.2045. Found: 358.2049.

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General Procedure for the Synthesis of 5-Aalkyl or 5-Aryl-4-chloromethylimidazolidin-2-one: To a solution of {1-[1′(R)-α-methylbenzyl]aziridin-2(R)-yl}-methylamine (310 mg, 1.05 mmol) in 15 mL of THF under nitrogen atmosphere was added NaH (144 mg, 6 mmol) at -10 °C. The mixture was stirred for 1 h at -10 °C. To the mixture was slowly added triphosgene solution (0.356 g, 1.2 mmol) in THF (5 mL) at -10 °C. The mixture was stirred for 2 h at -10 °C. The reaction was quenched with H2O at -10 °C and warmed to r.t. The aqueous layer was extracted with CH2Cl2 (10 mL × 5). The combined organic extract was dried over MgSO4 and the solvent was evaporated in vacuo to give the crude product as a white solid which was purified by silica gel flash chromatography to give analytically pure product. Compound 6a: colorless oil. 1H NMR (200 MHz, CDCl3):
δ = 0.82 (d, J = 6.2 Hz, 3 H), 1.50 (d, J = 7.4 Hz, 3 H), 2.92 (dt, J = 7.0 Hz, 3.2 Hz, 1 H), 3.32 (dd, J = 11.4 Hz, 7.6 Hz, 1 H), 3.42 (dd, J = 11.4 Hz, 3.2 Hz, 1 H), 3.65 (s, 3 H), 3.90 (qd, J = 6.2 Hz, J = 3.2 Hz, 1 H), 5.25 (q, J = 7.4 Hz, 1 H), 6.72-6.78 (m, 2 H), 7.11-7.27 (m, 7 H). 13C NMR (50.3 MHz, CDCl3): δ = 18.7, 19.4, 45.5, 51.2, 54.6, 55.4, 58.8, 114.1, 123.1, 127.3, 127.7, 128.6, 131.4, 139.8, 156.2, 156.8. HRMS (EI) calcd for C20H23ClN2O2: 358.1448. Found: 358.1453.