Download PDF
Synlett 2009(8): 1265-1268  
DOI: 10.1055/s-0028-1088125
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Novel Synthesis of Chiral Unactivated 2-Aryl-1-benzylaziridines

Erika Leemans, Sven Mangelinckx, Norbert De Kimpe*
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
Fax: +32(9)2646243; e-Mail: norbert.dekimpe@ugent.be;
Further Information

Publication History

Received 6 February 2009
Publication Date:
08 April 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

Chiral (R S ,R)- and (R S ,S)-N-(tert-butylsulfinyl)-2-aryl-aziridines were transformed into (R)- and (S)-2-aryl-1-benzylaziridines via a short three-step procedure. Deprotection and ring opening of (R S ,R)- and (R S ,S)-N-sulfinyl-2-arylaziridines (95-99% de) in acid medium afforded 2-aryl-2-chloroethylamine hydrochlorides in high yield (83-90%). These intermediates were converted into the corresponding chiral N-(benzylidene)-β-aryl-β-chloro-amines in good yield (78-85%). Subsequent reduction of the synthesized ald­imines afforded chiral 2-aryl-1-benzylaziridines in good to excellent yield (74-94%) and enantiomeric excess (83-99% ee). The enantiomeric purity of the chiral aldimines and aziridines was established by NMR spectroscopy using Pirkle alcohol as the chiral solvating agent.

Key words

chiral aziridines - asymmetric synthesis - ring opening - ring closure - haloimines

1

Postdoctoral Fellow of the Research Foundation-Flanders (FWO).

16

( R S , R )- N -( tert -Butylsulfinyl)-2-(4-methylphenyl)-aziridine (2d)
Prepared according to a previously described method, see ref. 11a. ¹H NMR (300 MHz, CDCl3): δ = 1.29 (s, 9 H), 1.99 (d, J = 3.9 Hz, 1 H), 2.34 (s, 3 H), 2.97 (d, J = 7.2 Hz, 1 H), 3.09 (dd, J = 7.2, 3.9 Hz, 1 H), 7.13-7.20 (m, 4 H). ¹³C NMR (75 MHz, CDCl3): δ = 21.2, 22.8, 28.6, 34.7, 57.4, 126.3, 129.2, 134.6, 137.5. IR (ATR): νmax = 1063, 1362, 1457, 1681, 2960, 3346 cm-¹. MS (ES, pos. mode): m/z (%) = 238(100) [M + H+]. [α]D -238.5 (c 1.15, CH2Cl2); mp 106.0-107.0 ˚C. Anal. Calcd for C13H19NOS: C, 65.78; H, 8.07; N, 5.90; S, 13.51. Found: C, 65.44; H, 8.35; N, 6.11; S, 13.28.

17

( S )-2-Chloro-2-(4-methylphenyl)ethylamine Hydrochloride (3d)
Prepared according to a previously described method, see ref. 11a,b. ¹H NMR (300 MHz, D2O): δ = 2.31 (s, 3 H), 3.19 (dd, J = 12.7, 4.4 Hz, 1 H), 3.26 (dd, J = 12.7, 8.7 Hz, 1 H), 4.93 (dd, J = 8.7, 4.4 Hz, 1 H), 7.26-7.32 (m, 4 H). ¹³C NMR (75 MHz, D2O): δ = 20.8, 45.8, 70.0, 126.6, 130.1, 137.1, 139.6. IR (ATR): νmax = 1146, 1510, 1603, 2361, 2958 cm-¹. MS (ES, pos. mode): m/z (%) = 152/154(100), 170/172(20) [M + H+]. [α]D +52.6 (c 1.01, MeOH); mp 173.6-174.6 ˚C. Anal. Calcd for C9H13NCl2: C, 52.45; H, 6.36; N, 6.80. Found: C, 52.52; H, 6.42; N, 6.57.

18

Preparation of ( S )- N -Benzylidene-[2-chloro-2-(4-methylphenyl)ethyl]amine (4d)
Triethylamine (0.09 g, 0.93 mmol) was added to a solution of (S)-2-chloro-2-(4-methylphenyl)ethylamine hydro-chloride (3d, 0.15 g, 0.88 mmol), MgSO4 (0.15 g, 1.27 mmol), and benzaldehyde (0.09 g, 0.88 mmol) in CH2Cl2 (15 mL). The reaction was stirred for 7 h at 0 ˚C. The suspension was subsequently filtered, and the solvent was evaporated. Diethyl ether (15 mL) was added and the obtained mixture was again filtered and evaporated, yielding 4d which was purified by recrystallization from Et2O (0.18 g); yield 83%. ¹H NMR (300 MHz, CDCl3): δ = 2.35 (s, 3 H), 4.02 (ddd, J = 12.5, 8.5, 1.1 Hz, 1 H), 4.21 (ddd, J = 12.5, 5.0, 1.7 Hz, 1 H), 5.24 (dd, J = 8.5, 5.0 Hz, 1 H), 7.16-7.45 and 7.72-7.76 (m, 9 H), 8.28 (s, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 21.2, 62.7, 69.0, 127.2, 128.3, 128.6, 129.3, 131.0, 135.8, 137.0, 138.3, 163.7. IR (ATR): νmax = 1449, 1514, 1645, 2361, 2916 cm-¹. MS (ES, pos. mode): m/z (%): 258/260(100) [M + H+]. [α]D +55.8 (c 0.70, CH2Cl2); mp 79.4-80.4 ˚C. Anal. Calcd for C16H16NCl: C, 74.55; H, 6.26; N, 5.43. Found: C, 74.89; H, 6.37; N, 5.20.

21

Ghorai and co-workers have concluded, based on experimental results, that the Lewis acid mediated nucleophilic ring opening of activated 2-phenylaziridines occurs via an SN2 pathway, see ref. 14c-e.

23

Preparation of ( R )-1-Benzyl-2-(4-methylphenyl)-aziridine (8d)
To a stirred solution of aldimine 4d (0.12 g, 0.47 mmol) in MeOH (15 mL) was added NaBH4 (0.02 g, 0.47 mmol), and the reaction mixture was brought to reflux for 3 h. Afterwards, a sat. soln of NaHCO3 (10 mL) was added, and the organic solvent was evaporated. The resulting mixture was extracted with CH2Cl2 (3 × 15 mL), and the combined organic layers were dried (MgSO4) and filtered to afford
1-benzyl-2-(4-methylphenyl)aziridine (8d, 0.09 g) in pure form after removal of the solvent in vacuo; yield 92%. ¹H NMR (300 MHz, CDCl3): δ = 1.82 (d, J = 6.6 Hz, 1 H), 1.97 (d, J = 3.3 Hz, 1 H), 2.32 (s, 3 H), 2.47 (dd, J = 6.6, 3.3 Hz, 1 H), 3.58 (d, J = 13.8 Hz, 1 H), 3.70 (d, J = 13.8 Hz, 1 H), 7.08-7.38 (m, 9 H). ¹³C NMR (75 MHz, CDCl3): δ = 21.1, 37.8, 41.4, 64.8, 126.1, 126.9, 127.8, 128.3, 129.0, 136.5, 137.1, 139.2. IR (ATR): νmax = 1026, 1452, 1517, 2826, 3028 cm-¹. MS (ES, pos. mode): m/z (%) = 224(100) [M + H+]. [α]D -55.8 (c 1.01, CH2Cl2). Anal. Calcd for C16H17N: C, 86.05; H, 7.67; N, 6.27. Found: C, 86.21; H, 7.83; N, 5.96.