LETTER
Novel Synthesis of Chiral Unactivated 2-Aryl-1-benzylaziridines
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t-Bu
S
t-Bu
O
R
SR
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Jarvis, A. N.; Osborn, H. M. I.; Raphy, J.; Sweeney, J. B.
Chem. Commun. 1996, 2631.
1) NaBH4 (2 equiv)
MeOH (2 equiv)
THF, –78 °C, 1 h
N
O
N
S
Cl
2) KOH (3 equiv)
H2O–THF (1:1)
reflux, 16 h
R
R
1c R = F
1d R = Me
9a R = F 86%, 97% de
9b R = Me 76%, 95% de
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61, 8443.
1) dioxane⋅HCl
2) PhCHO (1 equiv)
Et3N (1.1 equiv)
MgSO4 (1.5 equiv)
CH2Cl2, 0 °C, 7 h
(10 equiv)
dioxane, r.t., 1 h
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2008, 2986.
H
N
Cl
NaBH4 (1 equiv)
MeOH, reflux, 3 h
S
N
R
R
R
11a 86%, 85% ee
11b 87%, 83% ee
10a 74%, 85% ee
10b 80%, 83% ee
Scheme 4
In conclusion, a short synthesis of the unactivated (R)- and
(S)-2-aryl-1-benzylaziridines 8 and 11 was developed in
high yield and good to excellent enantiomeric purity via a
three-step sequence from the activated (RS,R)- and (RS,S)-
N-(tert-butylsulfinyl)-2-arylaziridines 1 and 9. The enan-
tiomeric purity of the intermediate N-(benzylidene)-b-
aryl-b-chloroamines and aziridines was influenced by the
para-substituent of the aryl group. The synthesis of chiral
N-unactivated aziridines 8 and 11 is complementary to the
access towards chiral N-activated aziridines 2 and 9.
(12) Li, A.-H.; Dai, L.-X.; Aggarwal, V. K. Chem. Rev. 1997, 97,
2341.
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Acknowledgment
(14) (a) Cossy, J.; Bellosta, V. FR 2821354, 2002, Chem. Abstr.
2003, 138, 169957. (b) Allan, R. D.; Tran, H. W. Aust. J.
Chem. 1990, 43, 1123. (c) Ghorai, M. K.; Das, K.; Shukla,
D. J. Org. Chem. 2007, 72, 5859. (d) Ghorai, M. K.; Ghosh,
K. Tetrahedron Lett. 2007, 48, 3191. (e) Ghorai, M. K.;
Das, K.; Kumar, A.; Ghosh, K. Tetrahedron Lett. 2005, 46,
4103.
The authors are indebted to Ghent University (GOA) and the Re-
search Foundation-Flanders (FWO-Vlaanderen) for financial sup-
port of this research.
The authors are indebted to Prof. D. M. Hodgson for addressing im-
portant suggestions regarding the ring opening of chiral aziridines 2.
(15) For some reviews on the importance of phenylethylamines,
see: (a) Smith, T. A. Phytochemistry 1977, 16, 9.
(b) Juaristi, E.; Léon-Romo, J. L.; Reyes, A.; Escalante, J.
Tetrahedron: Asymmetry 1999, 10, 2441. (c) Juaristi, E.;
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References and Notes
(1) Postdoctoral Fellow of the Research Foundation-Flanders
(FWO).
(2) Aziridines and Epoxides in Organic Synthesis; Yudin, A. K.,
Ed.; Wiley-VCH: Weinheim, 2006.
(3) For selected examples with N-nucleophiles, see:
(a) Karikomi, M.; De Kimpe, N. Tetrahedron Lett. 2000, 41,
10295. (b) D’hooghe, M.; Van Speybroeck, V.; Van
Nieuwenhove, A.; Waroquier, M.; De Kimpe, N. J. Org.
Chem. 2007, 72, 4733.
(4) For a recent example of enzymatic resolution of unactivated
aziridines and their study in nucleophilic ring opening
reactions, see: Moran-Ramallal, R.; Liz, R.; Gotor, V. Org.
Lett. 2007, 9, 521.
(16) (RS,R)-N-(tert-Butylsulfinyl)-2-(4-methylphenyl)-
aziridine (2d)
Prepared according to a previously described method, see
ref. 11a. 1H NMR (300 MHz, CDCl3): d = 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): d = 21.2, 22.8, 28.6, 34.7, 57.4, 126.3,
129.2, 134.6, 137.5. IR (ATR): nmax = 1063, 1362, 1457,
1681, 2960, 3346 cm–1. MS (ES, pos. mode): m/z (%) =
238(100) [M + H+]. [a]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.
(5) (a) Gabriel, S. Ber. Dtsch. Chem. Ges. 1888, 21, 1049.
(b) Wenker, H. J. Am. Chem. Soc. 1935, 57, 2328.
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(6) Sinou, D.; Emziane, M. Tetrahedron Lett. 1986, 27, 4423.
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