Benzopyran Derivatives
FULL PAPER
Michael/aldol condensation product 3 was determined by chiral-phase
HPLC or GC analysis.
Compound3h : trans-Hept-2-enal (4 equiv, 0.325 mmol, in 0.875 mL tol-
uene) was added by syringe pump overnight at room temperature to a
stirred solution of catalyst (20 mol%, 0.05 mmol), 2-nitrobenzoic acid
(20 mol%, 0.05 mmol), and salicylaldehyde (0.25 mmol) in toluene
(0.5 mL). The product was purified by silica gel chromatography (pure
toluene) to give chromene-3-carbaldehyde 3h in 67% yield and with
87% ee as a clear oil. The enantiomeric excess was determined by HPLC
with a Daicel Chiralpak ODH column (n-hexane/iPrOH 99.2:0.8, l =
254 nm), 0.5 mLminÀ1; tR minor enantiomer = 16.7 min; tR major enan-
Compound3a : HPLC (Daicel Chiralpak AD, isohexanes/iPrOH 96:4,
flow rate 0.5 mLminÀ1, l = 254 nm): tR major isomer = 18.21 min; tR
minor isomer = 20.51 min; [a]2D5 = À65.1 (c = 0.4, CHCl3); 1H NMR
(400 MHz, CDCl3): d = 6.34 (s, 1H), 6.88 (d, J = 8.2 Hz, 1H), 6.95 (dt,
J = 7.4, 1.1 Hz, 1H), 7.28 (m, 3H), 7.34 (m, 2H), 7.41 (s, 1H), 7.46 (m,
2H), 9.65 ppm (s, 1H); 13C NMR (100 MHz, CDCl3): 74.6, 117.4, 120.2,
122.0, 127.0, 128.0, 128.8, 128.9, 129.4, 129.6, 133.9, 141.0 153.0,
190.2 ppm; HRMS (ESI): m/z: calcd for C16H13O2: 237.0910; found:
237.0913 [M+H]+.
1
tiomer = 17.0 min; [a]D = +31.9 (c = 0.7, CHCl3); H NMR (400 MHz,
CDCl3): d = 0.87 (t, J = 7.2 Hz, 3H), 1.25–1.56 (m, 7H), 1.70–1.80 (m,
1H), 5.27 (dd, J = 9.3, 3.1 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 6.97 (dt, J
= 7.5, 1.1 Hz, 1H), 7.19–7.21 (m, 2H), 7.30 (ddd, J = 8.2, 7.5, 1.5 Hz,
1H), 9.55 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): 14.1, 22.4, 27.3, 33.6,
73.5, 117.4, 120.5, 121.8, 129.3, 133.5, 135.8, 140.7, 154.8, 190.3 ppm;
HRMS (ESI): m/z: calcd for C14H17O2: 217.1223; found: 217.1222
[M+H]+.
Compound3b : HPLC (Daicel Chiralpak AS, isohexanes/iPrOH 80:20,
flow rate 0.5 mLminÀ1, l = 254 nm): tR major isomer = 46.97 min; tR
minor isomer = 74.27 min; [a]D = À70.6 (c = 1.0, CHCl3); 1H NMR
(400 MHz, CDCl3): d = 6.33 (s, 1H), 6.86 (d, J = 8.3 Hz, 1H), 6.96 (dt,
J = 7.4, 1.0 Hz, 1H), 7.23 (dd, J = 7.7, 1.6 Hz, 1H), 7.28 (dt, J = 7.9,
1.6 Hz, 1H), 7.56 (d, J = 8.8 Hz, 2H), 7.82 (s, 1H), 8.14 ppm (d, J =
8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): 74.0, 117.2, 119.9, 122.5, 122.6,
124.1, 128.2, 129.8, 133.8, 136.9, 146.2, 148.3 153.7, 170.0 ppm; HRMS
(ESI): m/z: calcd for C16H12NO4: 282.0761; found: 282.0753 [M+H]+.
Compound3i : This compound was prepared by the procedure used for
3h. The enantiomeric excess was determined by HPLC with an Daicel
Chiralpak ODH column (n-hexane/iPrOH 99.1:0.9,
l
=
254 nm),
0.5 mLminÀ1; tR minor enantiomer = 15.3 min, tR major enantiomer =
16.9 min; [a]D = +32.8 (c = 1.3, CHCl3); 1H NMR (300 MHz, CDCl3):
d = 0.91 (t, J = 7.2 Hz, 3H), 1.34–1.60 (m, 3H), 1.69–1.81 (m, 1H), 5.28
(dd, J = 9.6, 3.1 Hz, 1H), 6.88 (d, J = 8.1 Hz, 1H), 6.94 (dt, J = 7.4,
1.1 Hz, 1H), 7.19–7.21 (m, 2H), 7.30 (ddd, J = 8.1, 7.5, 1.7 Hz, 1H),
9.55 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d = 13.8, 18.5, 35.9, 73.3,
117.4, 120.5, 121.7, 129.3, 133.5, 135.7, 140.7, 154.8, 190.3 ppm; HRMS
(ESI): m/z: calcd for C13H15O2: 203.1067; found: 203.1076 [M+H]+.
Compound3c : HPLC (Daicel Chiralpak AS, isohexanes/iPrOH 80:20,
flow rate 0.5 mLminÀ1, l = 254 nm): tR major isomer = 46.11 min; tR
minor isomer
=
59.1 min; [a]D
=
À44.4 (c
=
1, CHCl3); 1H NMR
(400 MHz, CDCl3): d = 6.37 (s, 1H), 6.92 (d, J = 8.3 Hz, 1H), 6.99 (t, J
= 7.5 Hz, 1H), 7.28 (m, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.46
(d, J
= 8.4 Hz, 2H), 7.97, (d, J = 8.3 Hz, 2H), 9.66 ppm (s, 1H);
13C NMR (100 MHz, CDCl3): 73.5, 117.3, 118.7, 119.8, 122.6, 127.5, 129.3,
130.0, 132.6, 133.0, 134.0, 141.6, 144.5, 154.7, 190.1 ppm; HRMS (ESI):
m/z: calcd for C17H12NO2: 262.0863; found: 262.0859 [M+H]+.
Compound3j : The enantiomeric excess was determined by HPLC on
Daicel Chiralpak ODH with isohexanes/iPrOH 85:15 as the eluent: tR
Compound3d : HPLC (Daicel Chiralpak OD-H, isohexanes/iPrOH 95:5,
flow rate 0.5 mLminÀ1, l = 254 nm): tR major isomer = 26.32 min; tR
minor isomer = 29.52 min; [a]D = À60.6 (c = 0.9, CHCl3); 1H NMR
(300 MHz, CDCl3): d = 6.30 (s, 1H), 6.87 (d, J = 8.2 Hz, 1H), 6.97 (dt,
J = 7.4, 1.1 Hz, 1H), 7.22–7.34 (m, 6H), 7.43 (s, 1H), 9.65 ppm (s, 1H);
13C NMR (75 MHz, CDCl3): 73.6, 117.3, 120.0, 122.1, 128.3, 128.9, 129.6,
133.5, 134.0, 134.7, 137.7, 141.1, 154.7, 190.0 ppm; HRMS (ESI): m/z:
calcd for C16H12ClO2: m/z: 271.0520; found: 271.0518 [M+H]+.
major isomer
= 22.980 min; tR minor isomer = =
26.878 min; [a]2D5
À113.4 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d = 1.17 (t, J =
7.2 Hz, 3H), 3.75 (s, 3H), 4.11 (dq, J = 7.2, 4.4 Hz, 2H), 5.75 (s, 1H),
6.75 (d, J = 2.8 Hz, 1H), 6.91 (dd, J = 8.8, 2.8 Hz, 1H), 6.96 (d, J =
8.8 Hz, 1H), 7.29 (s, 1H), 9.62 ppm (s, 1H); 13C NMR (100 MHz,
CDCl3): d = 14.0, 55.7, 61.8, 70.3, 113.2, 117.8, 119.99, 120.02, 130.5,
140.7, 148.9, 154.7, 168.8, 188.8 ppm; HRMS (ESI): m/z: calcd for
C14H15O5: 262.0914; found: 263.0905 [M+H]+.
Compound3e : HPLC (Daicel Chiralpak OD-H, isohexanes/iPrOH 95:5,
flow rate 0.5 mLminÀ1, l = 254 nm): tR major isomer = 28.41 min; tR
minor isomer = 38.74 min; [a]D = À27.6 (c = 1, CHCl3); 1H NMR
(400 MHz, CDCl3): d = 6.30 (s, 1H), 6.80 (d, J = 8.2 Hz, 1H), 6.90 (t, J
= 7.7 Hz, 1H), 7.22 (d, J = 8.2 Hz, 2H), 7.24 (m, 1H), 7.31 (t, J =
7.9 Hz, 1H), 7.39 (d, J = 8.5 Hz, 2H), 7.42, (s, 1H), 9.64 ppm (s, 1H);
13C NMR (100 MHz, CDCl3): 73.8, 117.4, 119.7, 122.3, 123.0, 128.8, 129.8,
132.0, 133.6, 134.2, 138.3, 141.2, 154.7, 190.1 ppm; HRMS (ESI): m/z:
calcd for C16H12BrO2: 315.0015; found: 315.0009 [M+H]+.
Compound3k : The enantiomeric excess was determined by HPLC on
Daicel Chiralpak As with isohexanes/iPrOH 90:10 as the eluent: tR major
isomer = 40.857 min; tR minor isomer = 51.317 min; [a]2D5 = À109.3 (c
= 1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d = 1.20 (t, J = 6.8 Hz,
3H), 3.82 (s, 3H), 4.13 (dq, J = 6.8, 3.2 Hz, 2H), 5.81 (s, 1H), 6.54–6.58
(m, 2H), 7.16 (d, J
=
8.4 Hz, 1H), 7.30 (s, 1H), 9.57 ppm (s, 1H);
14.1, 55.7, 61.9, 70.8, 101.9, 109.9,
13C NMR (100 MHz, CDCl3): d
=
113.0, 127.0, 131.0, 141.2, 157.0, 164.7, 169.0, 188.6 ppm; HRMS (ESI):
m/z: calcd for C14H15O5: 263.0914; found: 263.0904 [M+H]+.
Compound3 f
:
HPLC (Daicel Chiralpak OD-H, isohexanes/iPrOH
254 nm): tR major isomer =
Compound3l : The enantiomeric excess was determined by HPLC on
Daicel Chiralpak ODH with isohexanes/iPrOH 85:15 as the eluent: tR
minor isomer
90:10, flow rate 0.5 mLminÀ1
,
l
=
= 35.808 min; tR major isomer = =
44.380 min; [a]2D5
22.62 min; tR minor isomer = 38.41 min; [a]D = À40.5 (c = 1, CHCl3);
1H NMR (400 MHz, CDCl3): d = 6.50 (s, 1H), 6.88 (d, J = 8.1 Hz, 1H),
6.95 (t, J = 7.8 Hz, 1H), 7.24 (s, 1H), 7.28 (d, J = 7.3 Hz, 2H), 7.43 (m,
2H), 7.45 (s, 1H), 7.50 (m, 2H), 7.80 (m, 2H), 9.71 ppm (s, 1H);
13C NMR (100 MHz, CDCl3): 74.5, 117.5, 120.5, 122.1, 125.0, 126.3, 126.4,
126.6, 127.8, 128.6, 128.8, 129.7, 131.1, 134.0, 141.3, 153.0, 190.2 ppm;
HRMS (ESI): m/z: calcd for C20H15O2: 287.1067; found: 286.1067
[M+H]+.
À225.1 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d = 1.13 (t, J =
7.2 Hz, 3H), 3.87 (s, 3H), 4.03–4.12 (m, 2H), 5.85 (s, 1H), 6.82–6.84 (m,
1H), 6.88–6.96 (m, 2H), 7.30 (s, 1H), 9.59 ppm (s, 1H); 13C NMR
(100 MHz, CDCl3): d = 13.9, 56.4, 61.8, 70.4, 116.5, 120.4, 121.4, 122.3,
129.9, 140.8, 144.2, 148.3, 168.5, 188.7 ppm; HRMS (ESI): m/z: calcd for
C14H15O5: 263.0914; found: 263.0920 [M+H]+.
Compound3m : The enantiomeric excess was determined by HPLC with
an ODH column (n-hexane/iPrOH 95:5, l = 254 nm), 1 mLminÀ1; tR
Compound3g : The enantiomeric excess was determined by HPLC on
Daicel Chiralpak ODH with isohexanes/iPrOH 90:10) as the eluent: tR
minor isomer = 24.53 min; tR major isomer = 26.54 min; [a]2D5 = À158.4
(c = 1.0, CHCl3); 1H NMR (300 MHz, CDCl3): d = 1.18 (t, J = 6.9 Hz,
3H), 4.12 (dq, J = 6.9, 2.1 Hz, 2H), 5.81 (s, 1H), 6.96–7.04 (m, 2H), 7.24
(dd, J = 7.2, 1.8 Hz, 1H), 7.32–7.37 (m, 2H), 9.63 ppm (s, 1H); 13C NMR
(75 MHz, CDCl3): d = 14.0, 61.9, 70.5, 117.1, 119.7, 122.6, 129.8, 130.0,
133.9, 140.8, 155.0, 168.7, 188.9 ppm; HRMS (ESI): m/z: calcd for
C13H13O4: 233.0808; found: 233.0808 [M+H]+; MALDI-TOF MS: m/z:
calcd fo C13H12O4: 255.0633; found: 255.0634 [M+Na]+.
minor enantiomer = 22.1 min, tR major enantiomer = 23.9 min; [a]D
=
À144.3 (c = 1, CHCl3); 1H NMR (400 MHz, CDCl3): d = 1.20 (t, J =
5.4 Hz, 3H), 4.54 (m, 2H), 5.89 (s, 1H), 6.94 (m, 1H), 7.05 (m, 1H), 7.16
(ddd, J
= 12.0, 8.3, 1.6 Hz, 1H), 7.36 (d, 1H), 9.66 ppm (s, 1H);
13C NMR (75 MHz, CDCl3): 13.9, 62.0, 70.5, 120.4 (d, J = 17.6 Hz), 121.8
(d, J = 1.9 Hz), 122.3 (d, J = 6.6 Hz), 124.7 (d, J = 3.6 Hz), 130.8, 139.6
(d, J = 4.0 Hz), 142.7 (d, J = 11.6 Hz), 151.1 (d, J = 247.4 Hz), 168.1,
188.5 ppm; HRMS (ESI): m/z: calcd for C13H12FO4: 251.0714; found:
251.0723 [M+H]+.
Chem. Eur. J. 2007, 13, 574 – 581
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
579