4
H.-J. Du et al. / Tetrahedron xxx (xxxx) xxx
(300 MHz, CDCl3)
d
7.49e7.25 (m, 4H), 6.98 (s, 2H), 6.35 (s, 2H),
C
14H14ClNO3Na [MþNa]þ 302.05544, found 302.05670.
5.13e5.01 (m, 2H), 3.62 (br s, 1H), 1.26 (d, J ¼ 6.3 Hz, 3H), 1.14 (d,
2l, light yellow oil, 46 mg, 87% yield, 87% ee [Daicel CHIRALPAK
J ¼ 6.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
173.1, 140.3, 134.8, 129.1,
AD-H (0.46 cm ꢂ 25 cm); (n-hexane/2-propanol ¼ 95/5); flow
128.1, 127.5, 127.2, 123.1, 109.2, 70.4, 67.9, 21.5; HRMS (ESI): Exact
mass calcd. for C15H17NO3Na [MþNa]þ 282.11006, found 282.11092.
2f, colorless oil, 55 mg, 89% yield, 79% ee [Daicel CHIRALPAK AD-
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 13.43
20
(major), 14.90 (minor) min]. [
a
]
¼ þ90.7 (c 0.3, MeOH); 1H NMR
D
(300 MHz, CDCl3)
d
7.29 (dd, J ¼ 8.6, 5.2 Hz, 1H), 7.20e7.01 (m, 2H),
H
(0.46 cm ꢂ 25 cm);
(n-hexane/2-propanol ¼ 95/5);
flow
6.88 (s, 2H), 6.32 (s, 2H), 5.02 (d, J ¼ 3.7 Hz, 1H), 4.27e4.12 (m, 2H),
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 23.42
3.62 (s, 1H), 1.23 (t, J ¼ 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 173.0,
20
(major), 27.30 (minor) min]. [
(300 MHz, CDCl3)
a]
¼ þ183.0 (c 0.3, MeOH); 1H NMR
161.8 (d, J ¼ 248.3 Hz), 137.0 (d, J ¼ 7.6 Hz), 136.4 (d, J ¼ 3.2 Hz),
129.2 (d, J ¼ 8.5 Hz), 123.2, 116.1 (d, J ¼ 22.8 Hz), 114.6, 114.3 (d,
J ¼ 23.6 Hz), 109.8, 68.3, 63.0, 14.3; HRMS (ESI): Exact mass calcd.
for C14H14FNO3Na [MþNa]þ 286.08499, found 286.08578.
D
d
7.48e7.29 (m, 8H), 7.25e7.17 (m, 1H), 6.94e6.91
(m, 2H), 6.36e6.32 (m, 2H), 5.27e5.08 (m, 2H), 4.68 (s, 1H), 3.68 (br
s, 1H); 13C NMR (75 MHz, CDCl3)
d
173.3, 140.4, 134.8, 134.4, 129.3,
128.5, 128.4, 128.2, 128.0, 127.9, 127.4, 127.0, 123.1, 109.3, 68.2, 67.8;
HRMS (ESI): Exact mass calcd. for
330.11006, found 330.11111.
2m, colorless oil, 43 mg, 82% yield, 87% ee [Daicel CHIRALPAK
AD-H (0.46 cm ꢂ 25 cm); (n-hexane/2-propanol ¼ 90/10); flow
C
19H17NO3Na [MþNa]þ
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 8.40 (ma-
20
2g, colorless oil, 56 mg, 95% yield, 94% ee [Daicel CHIRALPAK
AD-H (0.46 cm ꢂ 25 cm); (n-hexane/2-propanol ¼ 95/5); flow
jor), 9.16 (minor) min]. [
a]
þ119.7 (c 0.3, MeOH); 1H NMR
D
(300 MHz, CDCl3)
d
7.41 (dd, J ¼ 8.4, 6.2 Hz, 1H), 7.20e7.01 (m, 2H),
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 28.79
6.96 (s, 2H), 6.35 (s, 2H), 5.11 (d, J ¼ 3.8 Hz, 1H), 4.41e4.08 (m, 2H),
20
(major), 19.49 (minor) min]. [
a
]
¼ þ203.7 (c 0.3, MeOH); 1H NMR
3.51 (d, J ¼ 4.1 Hz, 1H), 1.23 (t, J ¼ 7.1 Hz, 3H); 13C NMR (75 MHz,
D
(300 MHz, CDCl3)
d
7.97e7.89 (m, 2H), 7.54e7.47 (m, 3H), 7.29 (d,
CDCl3)
d
173.4, 162.3 (d, J ¼ 250.0 Hz), 141.7 (d, J ¼ 10.3 Hz), 130.4 (d,
J ¼ 8.3 Hz, 1H), 7.00 (d, J ¼ 1.2 Hz, 1H), 6.94 (s, 1H), 6.46 (s, 2H), 5.07
J ¼ 3.6 Hz), 129.5 (d, J ¼ 9.4 Hz), 122.9, 115.2 (d, J ¼ 21.3 Hz), 114.4 (d,
J ¼ 23.4 Hz), 109.8, 67.6, 62.5, 13.9; HRMS (ESI): Exact mass calcd.
for C14H14FNO3Na [MþNa]þ 286.08499, found 286.08608.
(s, 1H), 4.32e3.99 (m, 2H), 3.72 (br s, 1H), 1.22 (t, J ¼ 7.1 Hz, 3H); 13
C
NMR (75 MHz, CDCl3) d 173.6, 136.5, 133.6, 133.3, 131.8, 129.3, 127.7,
127.5, 127.1, 124.8, 123.8, 123.4, 109.1, 108.8, 68.4, 62.4, 14.0; HRMS
(ESI): Exact mass calcd. for C18H17NO3Na [MþNa]þ 318.11006, found
318.11054.
2n, brown oil, 28 mg, 50% yield, 86% ee [Daicel CHIRALPAK AD-H
(0.46 cm ꢂ 25 cm);
(n-hexane/2-propanol ¼ 95/5);
flow
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 29.71
¼ þ133.7 (c 0.3, MeOH); 1H NMR
20
2h, colorless oil, 50 mg, 96% yield, 91% ee [Daicel CHIRALPAK
AD-H (0.46 cm ꢂ 25 cm); (n-hexane/2-propanol ¼ 95/5); flow
(major), 27.60 (minor) min]. [
a]
D
(300 MHz, CDCl3)
d
7.33 (d, J ¼ 8.7 Hz, 1H), 7.02e6.92 (m, 3H), 6.86
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 18.37
(d, J ¼ 2.2 Hz, 1H), 6.34 (s, 2H), 5.05 (s, 1H), 4.21e4.14 (m, 2H), 3.84
20
(major), 17.33 (minor) min]. [
a
]
D
¼ þ127.7 (c 0.3, MeOH); 1H NMR
(s, 3H), 3.48 (br s, 1H), 1.23 (t, J ¼ 7.1 Hz, 3H); 13C NMR (75 MHz,
(300 MHz, CDCl3)
d
7.31 (d, J ¼ 7.6 Hz, 1H), 7.21 (d, J ¼ 7.9 Hz, 1H),
CDCl3) d 173.8, 160.0, 141.4, 128.9, 126.6, 123.0, 114.3, 112.2109.3,
7.15 (s, 1H), 6.95 (d, J ¼ 1.7 Hz, 2H), 6.33 (d, J ¼ 1.7 Hz, 2H), 5.08 (s,
67.8, 62.3, 55.5, 14.0; HRMS (ESI): Exact mass calcd. for C15H18NO
1H), 4.30e4.04 (m, 2H), 3.54 (br s, 1H), 2.39 (s, 3H), 1.26e1.18 (m,
[MþH]þ 276.12303, found 276.12439.
3H); 13C NMR (75 MHz, CDCl3)
d
174.1, 140.6, 139.9, 132.0, 129.4,
2o, colorless oil, 26 mg, 41% yield, 53% ee [Daicel CHIRALPAK
AD-H (0.46 cm ꢂ 25 cm); (n-hexane/2-propanol ¼ 95/5); flow
128.3, 128.1, 123.5, 109.6, 68.4, 62.7, 21.4, 14.4; HRMS (ESI): Exact
mass calcd. for C15H17NO3Na [MþNa]þ 282.11006, found 282.11097.
2i, colorless oil, 42 mg, 81% yield, 89% ee [Daicel CHIRALPAK AD-
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 31.35
20
(major), 46.64 (minor) min]. [
a
]
D
¼ þ80.0 (c 0.3, MeOH); 1H NMR
H
(0.46 cm ꢂ 25 cm);
(n-hexane/2-propanol ¼ 99/1);
flow
(300 MHz, CDCl3)
d
7.56 (d, J ¼ 7.8 Hz, 2H), 7.49e7.30 (m, 7H), 7.19 (t,
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 43.42
J ¼ 7.3 Hz, 1H), 7.00e6.91 (m, 1H), 6.64 (dd, J ¼ 2.6, 1.8 Hz, 1H), 5.20
20
(major), 39.91 (minor) min]. [
(300 MHz, CDCl3)
a
]
¼ þ107.0 (c 0.1, MeOH); 1H NMR
(s, 1H), 4.32e3.90 (m, 2H), 3.52 (br s, 1H), 1.23 (t, J ¼ 7.1 Hz, 3H); 13
C
D
d
7.22 (s, 1H), 7.20 (s, 2H), 6.91 (d, J ¼ 1.8 Hz, 2H),
NMR (75 MHz, CDCl3) d 173.0, 139.7, 134.9, 134.0, 128.9, 128.2, 127.9,
6.31 (d, J ¼ 1.8 Hz, 2H), 5.05 (s, 1H), 4.25e4.13 (m, 2H), 3.47 (br s,
127.4, 126.7, 125.2, 124.6, 123.7, 119.3, 107.1, 67.5, 62.0, 13.5; HRMS
(ESI): Exact mass calcd. for C20H20NO3Na [MþNa]þ 322.14377,
found 322.14264.
1H), 2.39 (s, 3H), 1.22 (t, J ¼ 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
173.6, 138.1, 134.3, 129.9, 128.0, 127.1, 123.1, 109.0, 67.9, 62.2, 20.9,
13.9; HRMS (ESI): Exact mass calcd. for C15H17NO3Na [MþNa]þ
2p, colorless oil, 42 mg, 80% yield, 84% ee/86% ee (2/1 dr) [Daicel
CHIRALPAK OJ-H (0.46 cm ꢂ 25 cm); (n-hexane/2-propanol ¼ 98.5/
1.5); flow rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm;
tR ¼ 11.75 (major), 27.09 (minor) min (tR ¼ 15.89 (major), 51.81
282.11006, found 282.11138.
2j, colorless oil, 49 mg, 88% yield, 87% ee [Daicel CHIRALPAK AD-
H
(0.46 cm ꢂ 25 cm);
(n-hexane/2-propanol ¼ 95/5);
flow
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 12.63
(minor) min)]; 1H NMR (300 MHz, CDCl3)
d 7.40e7.30 (m, 4H),
20
(major), 10.86 (minor) min]. [
(300 MHz, CDCl3)
a
]
D
¼ þ151.7 (c 0.3, MeOH); 1H NMR
7.25e7.10 (m, 2H)*, 5.55 (s, 1H), 5.37 (s, 0.5H)*, 4.35e4.05 (m, 3H),
3.55e3.25 (m, 3H), 2.82 (appq, J ¼ 9.0 Hz,1H), 2.70 (appq, J ¼ 9.0 Hz,
0.5 H)*, 2.25e1.80 (m, 5H), 1.70e1.50 (m, 2H), 1.23 (t, J ¼ 7.1 Hz,
4.5H), 1.05 (d, J ¼ 6.0 Hz, 1.5H)*, 0.99 (d, J ¼ 6.0 Hz, 3H)*.
d
7.38 (s, 2H), 7.36 (s,1H), 6.94 (s, 2H), 6.35 (s, 2H),
5.10 (d, J ¼ 4.2 Hz, 1H), 4.23e4.12 (m, 2H), 3.59 (d, J ¼ 4.3 Hz, 1H),
1.23 (t, J ¼ 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 175.8, 143.9,
137.2, 135.7, 131.7, 130.9, 130.0, 125.6, 112.4, 70.2, 65.1, 16.5; HRMS
(ESI): Exact mass calcd. for C14H14ClNO3Na [MþNa]þ 302.05544,
found 302.05676.
4.2. Transformation of 2 g
2k, colorless oil, 45 mg, 81% yield, 83% ee [Daicel CHIRALPAK
AD-H (0.46 cm ꢂ 25 cm); (n-hexane/2-propanol ¼ 90/10); flow
To a solution of 2g (590 mg, 2 mmol) in MeOH was added NaOH
(8.0 mL, 5% aq.), the mixture was stirred at room temperature until
complete consumption, then purified by flash chromatography
(petroleum ether/ethyl acetate ¼ 1/1) to give 3g as white solid.
487 mg, 91% yield, 95% ee. [Daicel CHIRALPAK AD-H
(0.46 cm ꢂ 25 cm); (n-hexane/2-propanol ¼ 95/5, 0.5% TFA); flow
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 8.62 (ma-
jor), 7.04 (minor) min]. [
a]
¼ þ96.3 (c 0.3, MeOH); 1H NMR
20
D
(300 MHz, CDCl3)
d
7.43 (s, 1H), 7.37 (d, J ¼ 8.1 Hz, 1H), 7.25 (d,
J ¼ 8.2 Hz, 1H), 6.90 (s, 2H), 6.33 (s, 2H), 5.06 (d, J ¼ 3.6 Hz, 1H),
4.40e4.08 (m, 2H), 3.57 (d, J ¼ 4.1 Hz,1H),1.23 (t, J ¼ 7.0 Hz, 3H); 13
C
rate ¼ 1.0 mL/min; detection wavelength ¼ 254 nm; tR ¼ 19.85
20
NMR (75 MHz, CDCl3)
d
173.4, 139.3, 136.7, 134.4, 129.8, 129.1, 128.4,
(major), 13.64 (minor) min]. [
a
]
¼ þ170.7 (c 0.3, MeOH); 1H NMR
D
123.5, 110.1, 68.2, 63.1, 14.4; HRMS (ESI): Exact mass calcd. for
(300 MHz, CDCl3) d 7.84 (s, 2H), 7.60e7.40 (m, 3H), 7.23 (m, 1H),
Please cite this article as: H.-J. Du et al., Copper-catalyzed intramolecular redox reaction: Asymmetric synthesis of chiral 2-(1H-pyrrol-1-yl)-