the next step without further purification to avoid the racem-
ization: [R]20D ) -19.9 (c 0.96, CCl4), lit.21 [R]24D ) -19.5 (c 2.6,
CCl4).
enantiomers of 1,2-cyclohexane-linked bis-oxazolines. The
results are in good agreement with the observation in
the asymmetric cyclization-carbonylation of 2-propargyl-
1,3-dione,14 and similar to the results of 4,5-dioxolane-
1,2-linked bis-oxazoline-catalyzed asymmetric cyclopro-
panation and aziridination of olefins.2
After successful asymmetric aziridination of chalcones,
we attempted to apply the CuOTf-cHBOX complexes to
the aziridination of styrene under the optimized condi-
tions. The aziridinated products were obtained in 78-
88% yields, with only 6-15% ee values. S-cHBOX still
gave the highest enantioselectivity in the aziridination
of styrene.
In summary, three enantiomers of cHBOXes were
synthesized in one-pot reactions by using the correspond-
ing diacids and L-phenylglycinol as starting materials,
and were applied in the asymmetric aziridination of
chalcones with PhIdNTs as a nitrene precursor. The
results indicate that highly enantioselective aziridination
of chalcones with up to >99% ee has been achieved under
catalysis of (S,S)-1,2-bis[(S)-(4-phenyl)oxazolin-2-yl]cy-
clohexane, which is the most matched stereoisomer
among cyclohexane-linked bis-oxazolines. The results also
indicate that the enantioselectivity is not substituent-
dependent with respect to chalcones in the present case,
unlike AnBOXes.
General Procedure for the Synthesis of 1,2-Bis[(S)-(4-
phenyl)oxazolin-2-yl]cyclohexane. A 50 mL flask fitted with
a magnetic stirring bar was charged with a solution of L-
phenylglycinol (0.517 g, 3.77 mmol) and Et3N (1.40 mL, 9.42
mmol) in 5 mL of dry CH2Cl2. The solution was cooled in an ice
bath, and a solution of (S,S)-1,2-cyclohexanedicarboxylic dichlo-
ride (0.394 g, 1.89 mmol) in 19 mL of dry CH2Cl2 was added
dropwise. The resulting mixture was allowed to warm to room
temperature, and was stirred for 22 h. After addition of TsCl
(0.718 g, 3.77 mmol), DMAP (0.023 g, 0.189 mmol), and ad-
ditional Et3N (1.20 mL, 8.29 mmol), the resulting mixture was
stirred for 27 h at room temperature. The reaction was then
quenched with 16 mL of saturated aqueous NH4Cl, and a white
solid formed. Water (6 mL) was added to dilute the solution,
and the layers were separated after filtration to remove the
white solid. The aqueous layer was back-extracted with CH2Cl2
(2 × 8 mL). The combined organic layer was washed successively
with 30 mL of saturated aqueous NaHCO3 and brine, dried over
anhydrous Na2SO4, filtered, and concentrated to give crude
product, which was purified by column chromatography (silica
gel, acetone:petroleum ether, 1:7, v/v) to afford colorless crystals
of product. Although (R,R)- and (S,S)-1,2-bis[(S)-(4-phenyl)-
oxazolin-2-yl]cyclohexanes were prepared previously,14 no char-
acteristic data were reported. Their analytical data are given
here.
(S,S)-1,2-Bis[(S)-(4-phenyl)oxazolin-2-yl]cyclohexane (S-
cHBOX): colorless crystals, yield 53%, mp 122-122.5 °C; Rf )
0.09 (acetone:petroleum ether 1:4, v/v, silica gel plate); [R]20
)
D
+11.4 (c 0.58, CH2Cl2); IR (KBr, cm-1) v 1663 (CdN); H NMR
(400 MHz, CDCl3) δ 1.37-1.42 (m, 2H), 1.57-1.66 (m, 2H), 1.83-
1.84 (m, 2H), 2.13-2.17 (m, 2H), 2.84-2.86 (m, 2H), 4.02 (dd, J
) 8.4, 8.4 Hz, 2H), 4.55 (dd, J ) 8.4, 10.0 Hz, 2H), 5.15 (dd, J )
8.4, 10.0 Hz, 2H), 7.21-7.30 (m, 10H); 13C NMR (100.6 MHz,
CDCl3) δ 25.1, 30.2, 39.8, 69.4, 74.5, 126.6, 127.3, 128.5, 142.7,
170.5; MS (EI) m/z (relative intensity, %) 374 (M+, 94), 297 (M+
- Ph, 2), 256 (87), 228 (100, M+ - Ph - oxazolinyl), 120 (51),
104 (85), 91 (60). Anal. Cacld for C24H26N2O2: C, 76.98; H, 7.00;
N, 7.48. Found: C, 76.85; H, 6.96; N, 7.55.
1
Experimental Section
Synthesis of Chiral Ligand 1,2-Bis[(S)-(4-phenyl)oxazo-
lin-2-yl]cyclohexane (cHBOXes). trans-1,2-Cyclohexane-
dicarboxylic acid was prepared from cis-1,2-cyclohexanedicar-
boxylic anhydride as starting material according to the literature
procedure.18 (S,S)-Cyclohexane-1,2-dicarboxylic acid was ob-
tained via chemical resolution of trans-cyclohexane-1,2-dicar-
boxylic acid with optically pure R-phenylethylamine.19
(R,R)-1,2-Bis[(S)-(4-phenyl)oxazolin-2-yl]cyclohexane
Preparation of (S,S)-1,2-Cyclohexanedicarboxylic Acid.
(S,S)-1,2-Cyclohexanedicarboxylic acid was resolved by a modi-
fied reported method.19 To a solution of (S)-1-phenylethylamine
(6.80 g, 56.0 mmol) in EtOH (100 mL) was added racemic trans-
1,2-cyclohexanedicarboxylic acid (9.60 g, 55.8 mmol) at room
temperature. The mixture first became clear, and then a white
solid formed. Toluene (100 mL) was added after the mixture was
allowed to stir for another 3 h, and the reaction mixture was
brought to reflux until the solid was dissolved completely. The
solution was cooled, and colorless needle crystals were formed
and filtered to give colorless crystals (6.10 g), which were
recrystallized from hot EtOH/toluene (1:1) twice. The product
obtained was dissolved in 1 mol/L aqueous HCl, and was
extracted three times with Et2O (80 mL). The combined organic
phase was dried over anhydrous Na2SO4 and evaporated under
reduced pressure, affording the enantiomerically pure (S,S)-1,2-
cyclohexanedicarboxylic acid as colorless crystals (1.85 g, yield
19%): [R]20 ) +18.3 (c 1.03, acetone), lit.19 [R]25 ) +18.3
(R-cHBOX): yellow viscous oil, yield 21%; Rf
) 0.16
(acetone:petroleum ether 1:4, v/v, silica gel plate); [R]20D ) -107
(c 0.94, CH2Cl2); IR (KBr, cm-1) v 1663 (CdN); 1H NMR (300
MHz, CDCl3) δ 1.35-1.43 (m, 2H), 1.62-1.66 (m, 2H), 1.83-
1.86 (m, 2H), 2.09-2.14 (m, 2H), 2.82-2.85 (m, 2H), 4.02 (dd, J
) 8.1, 8.4 Hz, 2H), 4.58 (dd, J ) 8.1, 10.2 Hz, 2H), 5.14 (dd, J )
8.4, 10.2 Hz, 2H), 7.19-7.32 (m, 10H); 13C NMR (75.5 MHz,
CDCl3) δ 25.1, 30.1, 40.3, 69.4, 74.5, 126.6, 127.3, 128.5, 142.5,
170.5; MS (EI) m/z (relative intensity, %) 374 (M+, 82), 297 (M+
- Ph, 2), 256 (57), 228 (60, M+ - Ph - oxalyl), 120 (51), 104
(89), 91 (100). Anal. Cacld for C24H26N2O2: C, 76.98; H, 7.00; N,
7.48. Found: C, 76.81; H, 6.83; N, 7.64.
cis-1,2-Bis[(S)-(4-phenyl)oxazolin-2-yl]cyclohexane
(cis-cHBOX): yellow viscous oil, yield 40%; Rf
) 0.26
(acetone:petroleum ether 1:4, v/v, silica gel plate); [R]20D ) -13.0
(c 1.02, CH2Cl2); IR (KBr, cm-1) v 1663 (CdN); 1H NMR (200
MHz, CDCl3) δ 1.39-1.43 (m, 2H), 1.59-1.65 (m, 2H), 1.83-
1.86 (m, 2H), 2.11-2.17 (m, 2H), 2.83-2.87 (m, 2H), 4.02 (dd, J
) 8.2, 8.2 Hz, 2H), 4.55 (dd, J ) 8.2, 10.2 Hz, 2H), 5.15 (dd, J )
8.4, 10.2 Hz, 2H), 7.20-7.33 (m, 10H); 13C NMR (50 MHz, CDCl3)
δ 25.1, 20.3, 39.8, 69.4, 74.5, 126.6, 127.3, 128.6, 142.7, 170.5;
D
D
(c 1.00, acetone).
General Procedure for the Synthesis of 1,2-Cyclohex-
anedicarboxylic Dichloride. 1,2-Cyclohexanedicarboxylic acid
(0.432 g, 2.51 mmol) was treated with SOCl2 (1.49 g, 12.6 mmol)
in the presence of a catalytic amount of dry DMF, and the
mixture was allowed to stir for 41 h to give a colorless solution.
The solution was evaporated in vacuo to remove the excess SOCl2
to afford the clear liquid.
Racemic trans-1,2-cyclohexanedicarboxylic dichloride (126 °C,
10 mmHg) and cis-1,2-cyclohexanedicarboxylic dichloride (112-
114 °C, 4 mmHg) were obtained in vacuo in yields of 77 and
78%, respectively.
MS (EI) m/z (relative intensity, %) 374 (M+, 100), 297 (M+
-
Ph, 3), 256 (86), 228 (69), 120 (65), 104 (96), 91 (84); HRMS Calcd
for C24H26N2O2 (M+) 374.1994, found 374.2007.
General Procedure for the Asymmetric Aziridination
of Chalcones. A three-necked flask (25 mL) was charged with
chalcone 6 or olefin (1.50 mmol), cHBOX or BOX (0.06 mmol),
(20) Suga, H.; Kakehi, A.; Ibata, T.; Fudo, T.; Watanabe, Y.;
Kinoshita, Y. Bull. Chem. Soc. Jpn. 2003, 76, 189-199.
(21) Overberger, C. G.; Okamoto, Y.; Bulacovschi, V. Macromolecules
1975, 8, 31-36.
(S,S)-1,2-Cyclohexanedicarboxylic dichloride was obtained
after removal of solvent and excessive SOCl2, and was used in
J. Org. Chem, Vol. 70, No. 24, 2005 10157