LETTER
Ylide Azirination of Chiral Sulfinyl Imines
1987
(5) Representative Procedure as follows: To a solution of pre-
washed sodium hydride, (pentane, 3 equiv, 60% in mineral
oil), in DMSO, dry, (3 mL), was added trimethylsulfonium
iodide, (3 equiv). This was stirred at ambient temperature
under argon, and stirred for 10 min, until the cloudy mixture
went clear. At this point a solution of sulfinylimine, (1
equiv), in dry DMSO, (2 mL), was added dropwise to the
mixture. The reaction was then stirred at r.t. and the progress
monitored by thin layer chromatography. Once complete,
ice-cold brine (3 mL) was added, and the reaction stirred for
5 min. The resulting mixture was filtered through a pad of
celite, and the solution extracted with EtOAc (5 × 20 mL),
and concentrated under reduced pressure. The residue was
partitioned between 1:1 hexanes–Et2O and H2O, and the
organic fraction dried over Na2SO4, and concentrated under
reduced pressure. Purification by column chromatography
on alumina (Brockmann grade 3) eluting with hexanes–
EtOAc gave the products.
imines gave slightly decreased yields, which may be at-
tributable to their ability to enolise under the basic
reaction conditions. The increased steric bulk of the cy-
clohexyl imine is probably responsible for the higher
selectivity in this case (Table 2, entry 5).
In conclusion, the tert-butylsulfinyl group is a successful
acivating group/directing group for the synthesis of aziri-
dines from imines. Electron rich, electron poor, sterically
hindered and primary alkyl imines are all successful
substrates. Reports of our findings on the conversion of
these aziridines into functionalised heterocyclic scaffolds
will be reported in due course.
(6) Data for aziridines: N-[tert-Butyl-(R)-sulfinyl]-2-(S)-
phenylaziridine: [a]D20 +298 (c 0.88, CHCl3). IR: 1080,
2330, 2350, 2923 cm–1. MS: m/z (%) = [M + H ] 224.1(5),
104.0(100). HRMS: Calcd for C12H17NOS [M + H]
224.1109. Found: 224.1111. 1H NMR (400 MHz, CDCl3):
d = 1.18 (s, 9 H), 2.18 (d, 1 H, J = 3.6 Hz), 2.46 (d, 1 H,
J = 6.8 Hz), 3.61 (dd, 1 H, J = 3.6, 6.8 Hz), 7.30 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 22.9, 31.5, 31.9, 57.0,
126.9, 128.0, 128.8, 137.2. N-[tert-Butyl-(R)-sulfinyl]-2-
(S)-(2¢-phenylvinyl)-aziridine: [a]D20 +185 (c 0.5, CHCl3).
IR: 1070, 2360, 2918 cm–1. MS: m/z (%) = [M + H]
250.0(42), 96.1(100). HRMS: Calcd for C14H19NOS [M +
H]: 250.1256. Found: 250.1263. 1H NMR (400 MHz,
CDCl3): d = 1.18 (s, 9 H), 2.17 (broad, 1 H), 2.35 (d, 1 H,
J = 9.0 Hz), 3.20–3.30 (m, 1 H), 5.80–6.00 (dd, 1 H,
J = 11.4, 21.2 Hz), 6.80 (d, 1 H, J = 21.2 Hz), 7.30 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 22.1, 29.9, 35.0, 57.2,
126.6, 128.2, 128.9, 136.5. N-[tert-Butyl-(R)-sulfinyl]-2-
(S)-(4¢-methoxyphenyl)-aziridine: [a]D20 +68 (c 0.5,
CHCl3). IR, 2924, 1516, 1449, 1250, 1086 cm–1. MS: m/z
(%) = [M + H] 254.2(82), 149.2(100). HRMS: Calcd for
C13H19NO2S [M + H]: 254.1209. Found: 254.1209. 1H NMR
(400 MHz, CDCl3): d = 1.20 (s, 9 H), 2.08 (d, 1 H, J = 4 Hz),
2.36 (d, 1 H, J = 6.8 Hz), 3.50 (dd, 1 H, J = 4.0, 6.8 Hz), 3.74
(s, 3 H), 6.80 (s, 2 H), 7.12 (s, 2 H). 13C NMr (101 MHz,
CDCl3): d = 23.1, 31.4, 31.9, 55.5, 57.1, 114.2, 114.3, 128.0.
N-[tert-Butyl-(R)-sulfinyl]-2-(S)-(2¢-pyridyl)-aziridine:
[a]D20 +102 (c 1, CHCl3). IR: 1080, 1450, 1475, 2923 cm–1.
MS: m/z (%) = [M + H] 225.0(100). HRMS: Calcd for
C11H16N2OS: 225.1056. Found: 225.1058. 1H NMR (400
MHz, CDCl3): d = 1.18 (s, 9 H), 2.417 (d, 1 H, J = 6.8 Hz),
2.443 (d, 1 H, J = 4.0 Hz), 3.70 (dd, 1 H, J = 4.0, 6.8 Hz),
7.14 (dd, 1 H, J = 4.8, 7.6 Hz), 7.22 (d, 1 H, J = 8.0 Hz), 7.60
(dd, 1 H, J = 7.6, 8.0 Hz), 8.52 (d, 1 H, J = 4.8 Hz). 13C NMR
(75 MHz, CDCl3): d = 21.9, 28.7, 29.4, 56.1, 121.1, 121.9,
135.8, 149.1, 155.5. N-[tert-Butyl-(R)-sulfinyl]-2-(S)-(3¢-
pyridyl)-aziridine: [a]D20 +116 (c 1, CHCl3). IR: 1078,
1455, 1585, 2910 cm–1. MS: m/z (%) = [M + H] 225.1(4),
106.1(100). HRMS: Calcd for C11H16N2OS [M + H]:
225.1061. Found: 225.1061. 1H NMR (400 MHz, CDCl3):
d = 1.18 (s, 9 H), 2.23 (d, 1 H, J = 4.0 Hz), 2.52 (d, 1 H,
J = 6.8 Hz), 3.66 (1 H, J = 4.0, 6.8 Hz), 7.32 (m, 1 H), 7.58
(m, 1 H), 8.60 (broad, 2 H). 13C NMR (75 MHz, CDCl3):
d = 23.0, 29.5, 32.1, 57.2, 134.2, 148.9, 149.4. N-[tert-
Butyl-(R)-sulfinyl]-2-(S)-(2¢-furyl)-aziridine: [a]D20 +66
(c 0.5, CHCl3). IR: 1089, 2338, 2358, 2920 cm–1. MS: m/z
(%) = [M + H] 214.2(100). HRMS: Calcd for C10H15NO2S
[M + H]: 214.0896. Found: 214.0896. 1H NMR (400 MHz,
CDCl3): d = 1.14 (s, 9 H), 2.35 (dd, 1 H, J = 1.2, 7.2 Hz),
Figure 1 X-ray crystal structure of 2b
Acknowledgement
The authors thank Millennium Pharmaceuticals and EPSRC for a
CASE award (DM), and the EPSRC Mass Spectrometry Service at
the University of Wales, Swansea for carrying out high resolution
mass spectra. The author also acknowledges the use of the EPSRC’s
Chemical Database Service at Daresbury.7 We thank Dr. David
Hughes, University of East Anglia, for X-ray crystal structure deter-
mination.
References
(1) (a) García Ruano, J. L.; Fernández, I.; Hamdouchi, C.
Tetrahedron Lett. 1995, 36, 295. (b) García Ruano, J. L.;
Fernández, I.; del Prado Catalina, M.; Cruz, A. A.
Tetrahedron: Asymmetry 1996, 7, 3407.
(2) Davis, F. A.; Zhou, P.; Liang, C.-H.; Reddy, R. E.
Tetrahedron: Asymmetry 1995, 6, 1511.
(3) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87,
1353.
(4) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J.
A. J. Org. Chem. 1999, 64, 1278.
Synlett 2003, No. 13, 1985–1988 © Thieme Stuttgart · New York