Efficient Asymmetric Synthesis of 4H-Chromene Derivatives
n-hexane = 10:90, flow rate = 1.0 mL/min, λ = 254 nm): tR = 12.57
(major), 15.68 (minor) min.
[M]+ 390.1661; found 390.1704. HPLC (Daicel Chiralcel AD, 2-
propanol/n-hexane = 20:80, flow rate = 1.0 mL/min, λ = 254 nm):
tR = 8.74 (major), 12.17 (minor) min.
5i: Purified by flash chromatography (petroleum/EtOAc, 2:1) to af-
ford a white solid (27.4 mg, 79%, 81%ee). [α]22.6 = 51.5 (c = 0.132,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.14–1.18 (t, J =
6.8 Hz, 3 H), 1.93–2.08 (m, 2 H), 2.30–2.40 (m, 2 H), 2.55–2.63 (m,
2 H), 4.00–4.09 (m, 2 H), 4.71 (s, 1 H), 6.22 (s, 2 H), 6.18–7.24 (m,
4 H) ppm. HPLC (Daicel Chiralcel AD, 2-propanol/n-hexane =
20:80, flow rate = 1.0 mL/min, λ = 254 nm): tR = 6.45 (major), 9.36
(minor) min.
5p: Purified by flash chromatography (petroleum/EtOAc, 2:1) to
afford a white solid (23.2 mg, 64%, 81%ee). [α]23.0 = 46.7 (c = 0.12,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.11–1.14 (t, J =
7.2 Hz, 3 H), 1.92–2.04 (m, 2 H), 2.30–2.32 (m, 2 H), 2.52–2.59 (m,
2 H), 3.93–4.05 (m, 2 H), 4.90 (s, 1 H), 6.25 (s, 2 H), 7.36–7.44 (m,
3 H), 7.68–7.73 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
14.21, 20.22, 26.99, 34.01, 36.86, 59.67, 80.65, 118.03, 125.15,
125.57, 126.73, 127.00, 127.37, 127.46, 127.82, 132.26, 133.33,
143.49, 158.42, 163.04, 169.11, 196.48 ppm. HRMS: calcd. for
C22H21NO4 [M]+ 364.1504; found 364.1542. HPLC (Daicel Chi-
5j: Purified by flash chromatography (petroleum/EtOAc, 2:1) to af-
ford a white solid (28.6 mg, 80%, 77%ee). [α]23.1 = 61.8 (c = 0.110,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.11–1.14 (t, J =
6.8 Hz, 3 H), 1.92–2.08 (m, 2 H), 2.33–2.36 (m, 2 H), 2.57–2.65 (m, ralcel AD, 2-propanol/n-hexane = 30:70, flow rate = 1.0 mL/min,
2 H), 3.98–4.06 (m, 2 H), 4.82 (s, 1 H), 6.28 (s, 2 H), 7.44–7.46 (d, J λ = 254 nm): tR = 5.23 (major), 9.65 (minor) min.
= 8.8 Hz, 2 H), 8.07–8.09 (d, J = 8.4 Hz, 2 H) ppm. HPLC (Daicel
5q: Purified by flash chromatography (petroleum/EtOAc, 2:1) to
afford a white solid (23.9 mg, 75%, 69%ee). [α]23.0 = 52.5 (c =
0.099, CH2Cl2). H NMR (400 MHz, CDCl3): δ = 1.19–1.22 (t, J
= 7.2 Hz, 3 H), 1.98–2.04 (m, 2 H), 2.33–2.58 (m, 4 H), 4.09–4.15
(m, 2 H), 5.10 (s, 1 H), 6.23 (s, 2 H), 6.82–6.86 (m, 2 H), 7.03–7.04
(d, J = 4.8 Hz, 1 H) ppm. HPLC (Daicel Chiralcel AD, 2-propanol/
n-hexane = 20:80, flow rate = 1.0 mL/min, λ = 254 nm): tR = 7.46
(major), 10.35 (minor) min.
Chiralcel AD, 2-propanol/n-hexane = 20:80, flow rate = 1.0 mL/
min, λ = 254 nm): tR = 8.71 (major), 13.66 (minor) min.
1
5k: Purified by flash chromatography (petroleum/EtOAc, 2:1) to
afford a white solid (26.8 mg, 81%, 77%ee). [α]23.1 = 68.1 (c =
1
0.091, CH2Cl2). H NMR (400 MHz, CDCl3): δ = 1.12–1.15 (t, J
= 7.2 Hz, 3 H), 1.92–2.06 (m, 2 H), 2.27–2.38 (m, 2 H), 2.53–2.62
(m, 2 H), 4.00–4.06 (q, J = 7.2 Hz, 2 H), 4.70 (s, 1 H), 6.18 (s, 2
H), 6.86–6.91 (t, J = 8.8 Hz, 2 H), 7.21–7.25 (dd, J = 5.6, 8.4 Hz,
2 H) ppm. HPLC (Daicel Chiralcel AD, 2-propanol/n-hexane =
20:80, flow rate = 1.0 mL/min, λ = 254 nm): tR = 6.24 (major), 7.99
(minor) min.
5r: Purified by flash chromatography (petroleum/EtOAc, 3:1) to
afford a white solid (21.2 mg, 71%, 73%ee). [α]29.1 = 14.1 (c =
1
0.075, CH2Cl2). H NMR (600 MHz, CDCl3): δ = 1.90–2.04 (m, 2
H), 2.16–2.43 (m, 2 H), 2.44–2.59 (m, 2 H), 3.58 (s, 3 H), 4.73 (s,
1 H), 6.18 (br. s, 2 H), 7.10–7.13 (t, J = 7.2 Hz, 1 H), 7.19–7.22 (t,
J = 7.2 Hz, 2 H), 7.26–7.27 (d, J = 7.2 Hz, 2 H) ppm. 13C NMR
(150 MHz, CDCl3): δ = 20.18, 26.95, 33.54, 36.85, 50.97, 80.57,
118.27, 126.11, 127.93, 128.04, 145.87, 158.56, 163.04, 169.49,
196.48 ppm. HPLC (Daicel Chiralcel AD, 2-propanol/n-hexane =
10:90, flow rate = 1.0 mL/min, λ = 254 nm): tR = 14.60 (major),
21.08 (minor) min.
5l: Purified by flash chromatography (petroleum/EtOAc, 2:1) to af-
ford a white solid (29.7 mg, 76%, 74%ee). [α]19.7 = 13.5 (c = 0.104,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.14–1.17 (t, J =
7.2 Hz, 3 H), 1.94–2.07 (m, 2 H), 2.28–2.40 (m, 2 H), 2.50–2.65 (m,
2 H), 4.01–4.06 (q, J = 7.2 Hz, 2 H), 4.68 (s, 1 H), 6.20 (s, 2 H),
7.06–7.09 (t, J = 8.0 Hz, 1 H), 7.21–7.25 (t, J = 7.6 Hz, 2 H), 7.38
(s, 1 H) ppm. HPLC (Daicel Chiralcel AD, 2-propanol/n-hexane =
20:80, flow rate = 1.0 mL/min, λ = 254 nm): tR = 6.24 (major), 7.99
(minor) min.
5s: Purified by flash chromatography (petroleum/EtOAc, 3:1) to
afford a white solid (23.5 mg, 72%, 69%ee). [α]22.3 = 52.3 (c =
0.153, CH2Cl2). 1H NMR (600 MHz, CDCl3): δ = 0.94 (d, J =
6.2 Hz, 3 H), 1.21 (d, J = 6.2 Hz, 3 H), 1.91–2.04 (m, 2 H), 2.28–
2.36 (m, 2 H), 2.49–2.61 (m, 2 H), 4.70 (s, 1 H), 4.85–4.89 (m, 1
H), 6.16 (br. s, 1 H), 7.08–7.11 (t, J = 7.3 Hz, 1 H), 7.18–7.21 (t, J
= 7.4 Hz, 2 H), 7.26 (d, J = 7.1 Hz, 2 H) ppm. 13C NMR
(150 MHz, CDCl3): δ = 20.22, 21.58, 22.17, 26.97, 33.89, 36.88,
66.89, 81.12, 118.03, 125.98, 127.68, 128.39, 146.08, 158.13, 162.93,
168.67, 196.60 ppm. HPLC (Daicel Chiralcel AD, 2-propanol/n-
hexane = 10:90, flow rate = 1.0 mL/min, λ = 254 nm): tR = 10.11
(major), 13.81 (minor) min.
5m: Purified by flash chromatography (petroleum/EtOAc, 2:1) to
afford a white solid (29.7 mg, 76%, 83%ee). [α]20.5 = –8 (c = 0.10,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.12–1.16 (t, J =
7.2 Hz, 3 H), 1.92–2.06 (m, 2 H), 2.27–2.38 (m, 2 H), 2.50–2.61 (m,
2 H), 3.98–4.07 (m, 2 H), 4.68 (s, 1 H), 6.20 (s, 2 H), 7.14–7.16 (d, J
= 8.4 Hz, 2 H), 7.31–7.33 (d, J = 8.0 Hz, 2 H) ppm. HPLC (Daicel
Chiralcel AD, 2-propanol/n-hexane = 20:80, flow rate = 1.0 mL/
min, λ = 254 nm): tR = 6.51 (major), 9.77 (minor) min.
5n: Purified by flash chromatography (petroleum/EtOAc, 2:1) to
afford a white solid (27.4 mg, 72%, 79%ee). [α]20.7 = –16 (c = 0.10,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.11–1.15 (t, J =
7.2 Hz, 3 H), 1.92–2.07 (m, 2 H), 2.32–2.36 (m, 2 H), 2.55–2.60 (m,
2 H), 3.98–4.06 (m, 2 H), 4.78 (s, 1 H), 6.24 (s, 2 H), 7.38–7.40 (d, J
= 8.0 Hz, 2 H), 7.45–7.47 (d, J = 8.4 Hz, 2 H) ppm. HPLC (Daicel
Chiralcel AD, 2-propanol/n-hexane = 20:80, flow rate = 1.0 mL/
min, λ = 254 nm): tR = 5.22 (major), 6.63 (minor) min.
5t: Purified by flash chromatography (petroleum/EtOAc, 3:1) to af-
ford a white solid (23.9 mg, 70%, 77%ee). [α]29.1 = 16.1 (c = 0.114,
1
CH2Cl2). H NMR (600 MHz, CDCl3): δ = 0.96 (s, 3 H), 1.09 (s,
3 H), 1.14–1.17 (t, J = 7.1 Hz, 3 H), 2.14–2.24 (dd, J = 16.2 Hz, 2
H), 2.42 (s, 2 H), 3.99–4.06 (m, 2 H), 4.69 (s, 1 H), 6.17 (br. s, 2
H), 7.10 (s, 1 H), 7.18–7.21 (t, J = 7.4 Hz, 2 H), 7.25–7.26 (d, J =
7.0 Hz, 2 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 14.20, 27.41,
29.09, 32.24, 33.83, 40.66, 50.72, 59.67, 80.84, 116.82, 126.03,
127.77, 128.24, 145.79, 158.32, 161.35, 169.14, 196.41 ppm. HPLC
(Daicel Chiralcel AD, 2-propanol/n-hexane = 10:90, flow rate =
1.0 mL/min, λ = 254 nm): tR = 10.11 (major), 13.81 (minor) min.
5o: Purified by flash chromatography (petroleum/EtOAc, 2:1) to
afford a white solid (28.4 mg, 73%, 89%ee). [α]20.9 = –3.8 (c =
1
0.106, CH2Cl2). H NMR (400 MHz, CDCl3): δ = 1.15–1.18 (t, J
= 7.2 Hz, 3 H), 1.98–2.01 (m, 2 H), 2.31–2.36 (m, 2 H), 2.53–2.57
(m, 2 H), 4.02–4.12 (m, 2 H), 4.77 (s, 1 H), 6.22 (s, 2 H), 7.25–7.45
(m, 7 H), 7.53–7.55 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 14.26, 20.24, 26.99, 33.51, 36.91, 59.73, 80.62, 118.03,
126.61, 126.92, 127.00, 128.64, 128.67, 138.87, 1414.18, 145.20,
158.40, 163.17, 169.12, 196.67 ppm. HRMS: calcd. for C24H23NO4
Supporting Information (see footnote on the first page of this arti-
1
cle): HPLC traces, H and 13C NMR spectra, mass spectra.
Eur. J. Org. Chem. 2011, 137–142
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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