Synthesis of Optically Pure trans-Aziridines
FIGURE 5. Molecular structures, representative distances (Å), dihedral angles (deg), and energies (kcal·mol-1) of possible transition states TS3a
and TS3b between model anion II and model imine (S)-III that would afford trans- and cis-aziridines, respectively, and TS4 that would afford
diastereomeric trans-aziridine. The first value indicates the relative energy, with ZPE correction included, between structures TS3a, TS3b, and TS4
separately. Free energy correction is indicated in brackets. In the second row, the activation barriers with respect to II and (R)-III in s-cis conformation
(ZPE correction included, free energy correction is indicated in brackets) are indicated.
139.3, 127.0, 133.8, 132.7, 131.2, 130.5, 127.9, 125.0, 43.6, 25.0,
24.7, and 21.2.
CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.93-7.35 (m, 11H), 7.54,
7.31, 7.18, and 6.99 (two AA′BB′ systems, 8H), 4.41 and 3.73 (2d,
2H, J ) 4.2 Hz), 2.36 and 2.19 (2s, 6H); 13C NMR (75 MHz,
CDCl3) δ 143.2, 142.6, 141.9, 141.3, 140.7, 134.2, 133.3, 132.8,
131.5, 130.0, 129.6, 129.3, 129.0, 128.9, 128.2, 128.0, 127.7, 127.0,
126.7, 126.3, 125.9, 125.0, 53,4, 39.6, 21.5, and 21.2; HRMS calcd
for C25H20NOS (M+ - SOTol) 382.1266, found 382.1252.
trans-(2S,3S)-2-(Phenyl)-3-[(S)-2-(p-toluenesulfinyl)phenyl]-1-
[(R)-(p-toluenesulfinyl)]aziridine, 8a: eluent for chromatography
hexane/Et2O 1:4; yield 69%; white solid; mp 118-119 °C (hexane/
General Procedure for Aziridination Reactions Summarized
in Tables 1 and 2. To a solution of sulfonium salt (S)-3 (0.13 mmol)
in THF (2 mL) under argon at -78 °C was added LiHMDS (1 M
in THF, 0.13 mL, 0.13 mmol). After 10 min of stirring, the solution
of N-sulfinylimine12 [(S)-5a-e and (R)-5a-g (0.15 mmol)] in THF
(1 mL) was added and the stirring continued for another 10 min.
Then the reaction was hydrolyzed at -78 °C with 2 mL of water,
and the mixture was extracted with CH2Cl2 (3 × 4 mL). The organic
layers were dried over anhydrous MgSO4, and the solvent was
removed under reduced pressure. The residue was purified by flash
column chromatography.
Et2O); [R]20 ) -145.5 (c 0.6, CHCl3); 1H NMR (300 MHz,
D
CDCl3) δ 8.04 (dd, 1H, J ) 7.8, 1.1 Hz), 7.56, 7.41, 7.24, and
7.10 (two AA′BB′ systems, 8H), 7.51 (dd, 1H, J ) 7.8, 1.1 Hz),
7.38-7.28 (m, 7H), 4.35 and 3.75 (2d, 2H, J ) 4.3 Hz), 2.37 and
2.29 (2s, 6H); 13C NMR (75 MHz, CDCl3) δ 144.4, 142.7, 141.8,
141.6, 141.0, 133.3, 131.2, 130.0, 129.5, 129.2, 128.5, 128.4, 127.8,
126.2, 124.9, 124.8, 45.6, 39.0, 21.4, and 21.3; HRMS calcd for
C21H18NOS (M+ - SOTol) 332.1109, found 332.1106.
trans-(2S,3S)-2-(Phenyl)-3-[(S)-2-(p-toluenesulfinyl)phenyl]-1-
[(S)-(p-toluenesulfinyl)]aziridine, 6a: eluent for chromatography
hexane/Et2O 1:4; yield 50%; white syrup; [R]20D ) -160.8 (c 0.6,
CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.88 (d, 1H, J ) 8.4 Hz),
7.54, 7.30, 7.20, and 7.07 (two AA′BB′ systems, 8H), 7.46-7.34
(m, 8H), 4.28 and 3.60 (2d, 2H, J ) 4.2 Hz), 2.37 and 2.28 (2s,
6H); 13C NMR (75 MHz, CDCl3) δ 143.4, 142.6, 141.9, 141.4,
140.8, 134.2, 131.8, 131.5, 130.0, 129.7, 129.5, 129.0, 128.9, 128.5,
127.0, 125.9, 125.1, 53.3, 39.4, 21.5, and 21.3; HRMS calcd for
C21H18NOS (M+ - SOTol) 332.1109, found 332.1106.
trans-(2S,3S)-2-(p-Methoxyphenyl)-3-[(S)-2-(p-toluenesulfinyl)phe-
nyl]-1-[(R)-(p-toluenesulfinyl)]aziridine, 8b: eluent for chromatog-
raphy hexane/Et2O 1:2; yield 67%; white solid; mp 120-121 °C
1
(hexane/Et2O); [R]20 ) -351.9 (c 0.2, CHCl3); H NMR (300
D
MHz, CDCl3) δ 8.01 (dd, 1H, J ) 7.8, 1.1 Hz), 7.56, 7.38, 7.28,
7.24, 7.09, and 6.88 (three AA′BB′ systems, 12H), 7.54-7.44 (m,
1H), 7.42-7.33 (m, 1H), 7.19-7.15 (m, 1H), 4.46 and 3.59 (2d,
2H, J ) 4.3 Hz), 3.83 (s, 3H), 2.38 and 2.29 (2s, 6H); 13C NMR
(75 MHz, CDCl3) δ 159.7, 144.2, 142.8, 141.8, 141.6, 141.1, 133.9,
131.2, 130.1, 129.9, 129.7, 129.5, 129.0, 127.5, 126.1, 124.8, 113.8,
55.2, and 21.4 (C-2 and C-3 are missing); HRMS calcd for
C22H20NO2S (M+ - SOTol) 362.1215, found 362.1225.
trans-(2S,3S)-2-(p-Cyanophenyl)-3-[(S)-2-(p-toluenesulfinyl)phe-
nyl]-1-[(S)-(p-toluenesulfinyl)aziridine, 6c: eluent for chromatog-
raphy hexane/Et2O 1:2; yield 56%; white syrup; [R]20 ) -55.4
D
1
(c 1.0, CHCl3); H NMR (300 MHz, CDCl3) δ 7.87 (dd, 1H, J )
6.8, 1.8 Hz), 7.58, 7.49, 7.38, 7.32, 7.18, and 7.13 (three AA′BB′
systems, 12H), 7.55-7.42 (m, 3H), 4.44 and 3.57 (2d, 2H, J ) 4.2
Hz), 2.38 and 2.31 (2s, 6H); 13C NMR (75 MHz, CDCl3) δ 143.2,
142.6, 141.9, 140.7, 140.6, 137.1, 134.0, 132.3, 131.8, 131.7, 130.3,
130.1, 129.6, 129.1, 127.3, 125.9, 125.0, 124.6, 51.8, 39.5, 21.5,
and 21.4; HRMS calcd for C22H17N2OS (M+ - SOTol) 357.1062,
found 357.1054.
trans-(2S,3S)-2-(p-Cyanophenyl)-3-[(S)-2-(p-toluenesulfinyl)phe-
nyl]-1-[(R)-(p-toluenesulfinyl)]aziridine, 8c: eluent for chromatog-
raphy hexane/Et2O/CH2Cl2 1.2:1:1; yield 76%; white syrup; [R]20
D
) -262.2 (c 0.9, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.99 (d,
1H, J ) 7.7 Hz), 7.60, 7.49, 7.42, 7.41, 7.22, and 7.18 (three
AA′BB′ systems, 12H), 7.57-7.52 (m, 1H), 7.29-7.22 (m, 2H),
4.26 and 3.90 (2d, 2H, J ) 4.0 Hz), 2.37 and 2.33 (2s, 6H); 13C
NMR (75 MHz, CDCl3) δ 144.3, 142.1, 142.0, 140.7, 139.5, 132.6,
118.5, 112.1, 132.2, 131.5, 130.1, 129.6, 129.5, 129.0, 128.3, 126.1,
125.9, 124.6 and 21.4 (C-2 and C-3 are missing); HRMS calcd for
C22H17N2OS (M+ - SOTol) 357.1062, found 357.1054.
trans-(2S,3S)-2-(o-Bromophenyl)-3-[(S)-2-p-toluenesulfinyl)phe-
nyl]-1-[(S)-(p-toluenesulfinyl)]aziridine, 6d: eluent for chromatog-
raphy hexane/Et2O 2:1; yield 36%; white syrup; [R]20 ) -26.3
D
1
(c 1.0, CHCl3); H NMR (300 MHz, CDCl3) δ 7.92 (dd, 1H, J )
7.0, 1.5 Hz), 7.59-7.48 (m, 4H), 7.43, 7.27, 7.20, and 7.08 (two
AA′BB′ systems, 8H), 7.35-7.18 (m, 3H), 4.22 and 3.80 (2d, 2H,
J ) 4.3 Hz), 2.38 and 2.28 (2s, 6H); 13C NMR (75 MHz, CDCl3)
δ 144.0, 142.2, 142.0, 140.8, 132.1, 132.6, 131.3, 130.0, 129.6,
129.3, 127.9, 127.1, 126.6, 126.1, 125.0, 124.7, 50.6, 41.2, 21.5,
and 21.3; HRMS calcd for C21H17BrNOS (M+ - SOTol) 410.0214,
found 410.0219.
trans-(2S,3S)-2-(o-Bromophenyl)-3-[(S)-2-(p-toluenesulfinyl)phe-
nyl]-1-[(R)-(p-toluenesulfinyl)]aziridine, 8d: eluent for chromatog-
raphy hexane/Et2O 1:1; yield 75%; white syrup; [R]20 ) -232.3
D
1
(c 0.9, CHCl3); H NMR (300 MHz, CDCl3) δ 8.00 (d, 1H, J )
trans-(2S,3S)-2-(2-Naphthyl)-3-[(S)-2-(p-toluenesulfinyl)phenyl]-
1-[(S)-(p-toluenesulfinyl)]aziridine, 6e: eluent for chromatography
hexane/Et2O 1:3; yield 48%; white syrup; [R]20D ) -110.0 (c 1.0,
7.8 Hz), 7.57-7.40 (m, 4H), 7.58, 7.45, 7.23, and 7.15 (two AA′BB′
systems, 8H), 7.25-7.15 (m, 3H), 4.21 and 4.09 (2d, 2H, J ) 4.0
Hz), 2.39 and 2.33 (2s, 6H); 13C NMR (75 MHz, CDCl3) δ 144.6,
J. Org. Chem. Vol. 74, No. 11, 2009 4223