5
1H), 5.85 (s, 1H), 4.23 (ddd,
(s, 1H), 3.98 (s, 1H), 3.91 (t,
3.0 Hz, 1H), 3.63 (s, 1H), 3.49 (s, 1H), 2.65 – 2.42 (m, 4H),
2.30 (s, 6H), 2.16 – 2.00 (m, 1H), 1.83 (t, = 13.5 Hz,
1H).13C NMR (101 MHz, Chloroform-
) δ 178.31, 138.79,
129.11, 128.30, 127.57, 92.68, 88.91, 80.50, 72.24, 70.29 (d,
J
= 15.1, 9.1, 4.7 Hz, 3H), 4.11
= 42.0min [major(S)-enantiomer], tr = 45.6min [minor(R)-
ACCEPTED MANUSCRIPT
J
= 2.6 Hz, 1H), 3.85 (d,
J
=
enantiomer].
)-3-[1-(2,3-Dichloro-phenyl)-2-nitro-ethyl]-pentane-
2,4-dione(11f),colorless oil, 95% yield, 87% ee.1H NMR
(400 MHz, Chloroform- ) δ 7.46 (dd, = 8.0, 1.5 Hz, 1H),
7.21 (t, = 7.9 Hz, 1H), 7.09 (dd, = 7.9, 1.5 Hz, 1H), 4.91
– 4.77 (m, 2H), 4.69 (dd, = 12.0, 3.4 Hz, 1H), 4.60 (d,
9.4 Hz, 1H), 2.32 (s, 3H), 2.09 (s, 3H).Chiralpak AD-H
column, Hex: -Pro =99.5:0.5, 0.6mL/min, wavelength=210
nm. tr = 52.2min [major( )-enantiomer], tr = 59.0min
[minor( )-enantiomer].
)-3-[1-(3-Bromo-phenyl)-2-nitro-ethyl]-pentane-2,4-
dione(11g),white solid, 86% yield, 89% ee.1H NMR (400
MHz, Chloroform- ) δ 7.45 (ddq, = 8.0, 2.3, 1.2 Hz, 1H),
7.38 (t, = 1.8 Hz, 1H), 7.23 (t, = 7.8 Hz, 1H), 7.14 (dt,
= 7.9, 1.3 Hz, 1H), 4.70 – 4.58 (m, 2H), 4.36 (d, = 10.6 Hz,
1H), 4.23 (ddd, = 10.7, 7.6, 4.9 Hz, 1H), 2.32 (s, 1H), 2.02
(s, 2H).Chiralpak AD-H column, Hex: -Pro=98:2, 1mL/min,
wavelength=210 nm. tr =22.9min [major( )-enantiomer], tr =
25.8min [minor( )-enantiomer].
)-3-[1-(3-Methoxy-phenyl)-2-nitro-ethyl]-pentane-2,4-
dione(11h),yellow oil, 86% yield, 95%ee.1H NMR (400
MHz, Chloroform- ) δ 7.29 – 7.20 (m, 1H), 6.86 – 6.76 (m,
1H), 6.73 (d, = 2.2 Hz, 1H), 4.71 – 4.57 (m, 2H), 4.39 (dd,
= 10.7, 1.7 Hz, 1H), 4.28 – 4.16 (m, 1H), 3.80 (d, = 1.7
Hz, 3H), 2.32 (d, = 1.7 Hz, 3H), 1.99 (d, = 1.7 Hz,
3H).ChiralpakAD-H column, Hex: -Pro =90:10, 1mL/min,
wavelength=210 nm. tr =12.5 min [major( )-enantiomer], tr
= 16.2min [minor( )-enantiomer].
)-3-[1-(3,5-Dichloro-phenyl)-2-nitro-ethyl]-pentane-
2,4-dione(11i),colorless oil, 87%yield, 80% ee.1H NMR
(400 MHz, Chloroform- ) δ 7.33 (t, = 1.8 Hz, 1H), 7.12 (d,
= 1.8 Hz, 2H), 4.70 – 4.58 (m, 2H), 4.34 (d, = 10.4 Hz,
= 10.4, 7.6, 4.8 Hz, 1H), 2.33 (s, 3H), 2.09
-Pro=95:5, 1mL/min,
wavelength=210nm. tr=12.6min [major( )-enantiomer], tr =
14.9min [minor( )-enantiomer].
)-3-[1-(4-Fluoro-phenyl)-2-nitro-ethyl]-pentane-2,4-
dione(11j), white solid, 78% yield, 90% ee.1H NMR (400
MHz, Chloroform- ) δ 7.23 – 7.16 (m, 2H), 7.09 – 7.01 (m,
2H), 4.66 – 4.60 (m, 2H), 4.36 (d, = 10.8 Hz, 1H), 4.30 –
4.22 (m, 1H), 2.32 (s, 3H), 1.99 (s, 3H).Chiralpak AD-H
column, Hex: -Pro =85:15, 1mL/min, wavelength=210 nm.
(S
J
d
d
J
J
J
J
= 23.5 Hz), 67.69, 67.43, 65.66, 65.04, 60.32, 57.71, 45.13.
J
J =
HRMS(ESI) Calcd for C24H29F6FeN3OS+H (M+H)+:
464.1459, Found: 464.1446.
i
General procedure for asymmetric Michael addition
The catalyst 3a(5.55 mg, 0.01 mmol) was added to a vial
containing 2,4-pentanedione (0.4 mmol) and nitroolefin (0.2
mmol) in 1 mL of dried toluene. After 48 hours of stirring at
room temperature, TLC analysis indicated completion of the
reaction. The reaction mixture wasconcentrated and purified
by column chromatography to afford the Michael addition
S
R
(S
d
J
J
J
J
J
products 11a
-
11p. Spectral data match those previously
J
reported16.
i
(
S
)-3-(2-Nitro-1-phenyl-ethyl)-pentane-2,4-dione(11a)
white solid, 85%yield, 86% ee.1H NMR (400 MHz,
Chloroform- )δ7.35 – 7.29 (m, 3H), 7.19 (d, = 7.2 Hz,
2H), 4.68 – 4.59 (m, 2H), 4.38 (d, = 10.8 Hz, 1H), 4.29 –
4.21 (m, 1H), 2.29 (s, 3H), 1.94(s, 3H). ChiralpakAD-H
column, Hex: -Pro =90:10, 1mL/min, wavelength=210 nm.
tr =10.6 min [major( )-enantiomer], tr = 14.0 min [minor
,
S
R
d
J
(S
J
d
i
J
S
J
J
(R
)-enantiomer].
J
J
(S
)-3-[1-(2-Fluoro-phenyl)-2-nitro-ethyl]-pentane-2,4-
i
dione(11b),white solid, 90% yield, 91%ee.1H NMR (400
S
MHz, Chloroform-
1.9 Hz, 1H), 7.15 – 7.06 (m, 2H), 4.79 – 4.72 (m, 1H), 4.68
– 4.62 (m, 1H), 4.50 (q, = 3.3, 2.8 Hz, 2H), 2.32 (s, 3H),
2.04 (s, 3H).Chiralpak AD-H column, Hex: -Pro =95:5,
1mL/min, wavelength=210 nm. tr =15.0min [major( )-
enantiomer], tr = 17.5min [minor( )-enantiomer].
)-3-[1-(2-Chloro-phenyl)-2-nitro-ethyl]-pentane-2,4-
dione(11c), White solid, 89% yield, 97% ee.1H NMR (400
MHz, Chloroform- ) δ 7.49 – 7.44 (m, 1H), 7.31 – 7.25 (m,
2H), 7.20 – 7.15 (m, 1H), 4.86 (dd, = 12.2, 6.6 Hz, 1H),
4.77 (ddd, = 10.4, 6.6, 3.9 Hz, 1H), 4.68 (dd, = 12.2, 4.0
Hz, 1H), 4.62 (d, = 10.0 Hz, 1H), 2.31 (s, 3H), 2.06 (s,
3H).ChiralpakAD-H column, Hex: -Pro =98:2, 1mL/min,
wavelength=210nm.tr=16.1 min [major( )-enantiomer], tr =
17.6min [minor( )-enantiomer].
)-3-[1-(2-Bromo-phenyl)-2-nitro-ethyl]-pentane-2,4-
dione(11d),white solid, 88% yield, 99% ee.1H NMR (400
MHz, Chloroform- ) δ7.65 (d, = 7.9 Hz, 1H), 7.32 (td,
7.5, 1.1 Hz, 1H), 7.23 – 7.14 (m, 2H), 4.86 (dd, = 12.0, 6.4
Hz, 1H), 4.79 – 4.73 (m, 1H), 4.69 (dd, = 12.2, 3.8 Hz,
1H), 4.63 (d, = 9.8 Hz, 1H), 2.31 (s, 3H), 2.06 (s, 3H).
Chiralpak AD-H column, Hex: -Pro =98:2, 1mL/min,
wavelength=210 nm. tr =20.7 min [major( )-enantiomer], tr
= 22.1 min [minor( )-enantiomer].
)-3-[2-Nitro-1-(2-nitro-phenyl)-ethyl]-pentane-2,4-
dione(11e),white solid, 67% yield, 91% ee.1H NMR (400
MHz, Chloroform- ) δ 7.96 (dd, = 8.1, 1.4 Hz, 1H), 7.64 –
7.48 (m, 2H), 7.38 (dd, = 7.8, 1.4 Hz, 1H), 5.00 (dd,
13.4, 7.1 Hz, 1H), 4.86 (dd, = 13.4, 3.7 Hz, 1H), 4.79 –
4.66 (m, 2H), 2.33 (s, 3H), 2.15 (s, 3H).Chiralpak AD-H
column, Hex: -Pro =98:2, 1mL/min, wavelength=210 nm. tr
d
) δ 7.36 – 7.29 (m, 1H), 7.19 (td,
J
= 7.7,
R
(S
J
i
d
J
S
J
J
R
1H), 4.22 (ddd, J
(s, 3H).Chiralpak AD-H column, Hex:i
(S
S
d
R
J
(S
J
J
J
d
i
J
S
R
i
(S
tr =9.8min [major(S)-enantiomer], tr = 18.0min [minor(R)-
enantiomer].
d
J
J
=
(S)-3-[1-(4-Chloro-phenyl)-2-nitro-ethyl]-pentane-2,4-
J
dione(11k),white solid, 85% yield, 87% ee.1H NMR (400
MHz, Chloroform-d) δ 7.36 – 7.30 (m, 2H), 7.19 – 7.13 (m,
J
J
2H), 4.68 – 4.59 (m, 2H), 4.35 (d,
4.20 (m, 1H), 2.32 (s, 3H), 2.00 (s, 3H).Chiralpak AD-H
column, Hex: -Pro =80:20, 1mL/min, wavelength=210 nm.
J = 10.7 Hz, 1H), 4.29 –
i
S
i
R
tr =8.5min [major(S)-enantiomer], tr = 20.8min [minor(R)-
(S
enantiomer].
(
S
)-3-[1-(4-Bromo-phenyl)-2-nitro-ethyl]-pentane-2,4-
dione(11l),white solid, 82% yield, 93%ee.1H NMR (400
MHz, Chloroform- ) δ 7.52 – 7.44 (m, 2H), 7.12 – 7.06 (m,
2H), 4.68 – 4.57 (m, 2H), 4.35 (d, = 10.7 Hz, 1H), 4.23
(ddd, = 10.7, 7.4, 5.2 Hz, 1H), 2.32 (s, 3H), 2.00 (s, 3H).
Chiralpak AD-H column, Hex: -Pro =80:20, 1mL/min,
d
J
J
J
=
d
J
J
J
i
i