Multi-Functionalized Polyheterocyclic Benzopyran Derivatives
(6S,6aR,10aR)-2-Chloro-7-imino-10-methyl-6a-nitro-6,9-diphenyl-
1717, 1658, 1564, 1476, 767 cm–1. HRMS (ESI): calcd. for
6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-8-carbonitrile (5fa):
C28H23N3O4 + Na 488.1579; found 488.1588. [α]2D5 = –23.9 (c =
1
18.8 mg, 40% yield. H NMR (400 MHz, CDCl3): δ = 10.85 (s, 1 0.30, CH2Cl2), 91% ee; the enantiomeric ratio was determined by
H), 7.56–7.54 (m, 3 H), 7.40–7.36 (m, 5 H), 7.32–7.28 (m, 4 H),
HPLC on Chiralpak IC column (30% 2-propanol/hexane, 1 mL/
7.05–7.02 (m, 1 H), 6.09 (s, 1 H), 4.20 (d, J = 5.7 Hz, 1 H), 3.50– min), tminor = 11.87 min, tmajor = 14.46 min.
3.46 (m, 1 H), 1.21 (d, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz,
(6S,6aR,10aR)-7-Amino-10-methyl-6a-nitro-6-phenyl-9-(p-tolyl)-
CDCl3): δ = 165.7, 159.7, 151.7, 135.9, 131.1, 130.1, 129.3, 129.2,
128.1, 128.0, 127.8, 126.9, 119.3, 89.7, 41.4, 18.7 ppm. IR (KBr):
3338, 3241, 2937, 2197, 1713, 1658, 1560, 1472 cm–1. HRMS (ESI):
6a,10a-dihydro-6H-benzo[c]chromene-8-carbonitrile (4ab): 18.4 mg,
1
41% yield. H NMR (400 MHz, CDCl3): δ = 7.39–7.29 (m, 6 H),
7.20–7.18 (m, 3 H), 7.08–7.00 (m, 4 H), 5.96 (s, 1 H), 5.22 (s, 2 H),
4.16–4.11 (m, 1 H), 2.36 (s, 3 H), 1.94 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 152.7, 147.6, 137.6, 134.4, 133.7, 129.5,
129.5, 129.1, 129.0, 128.7, 128.3, 126.7, 126.2, 122.1, 117.0, 116.0,
29.6, 21.2, 14.1 ppm. IR (KBr): 3350, 3253, 2938, 2212, 1681, 1649,
1561, 1464 cm–1. HRMS (ESI): calcd. for C28H23N3O3 + Na
472.1633; found 472.1641. [α]2D5 = +29.1 (c = 0.27, CH2Cl2), 90%
ee; the enantiomeric ratio was determined by HPLC on Chiralpak
OD column (10% 2-propanol/hexane, 1 mL/min), tmajor = 7.50 min,
tminor = 9.20 min.
calcd. for C27H20ClN3O3 + Na 492.1085; found 492.1084. [α]2D5
=
+39.5 (c = 0.85, CH2Cl2), 84% ee; the enantiomeric ratio was deter-
mined by HPLC on Chiralpak OD column (30% 2-propanol/hex-
ane, 1 mL/min), tminor = 9.035 min, tmajor = 10.77 min.
(6S,6aR,10aR)-7-Amino-2-bromo-10-methyl-6a-nitro-6,9-diphenyl-
6a,10a-dihydro-6H-benzo[c]chromene-8-carbonitrile (4ha): 22.6 mg,
1
44% yield. H NMR (400 MHz, CDCl3): δ = 7.49–7.47 (m, 2 H),
7.42–7.29 (m, 5 H), 7.19–7.00 (m, 6 H), 5.89 (s, 1 H), 5.15 (s, 2 H),
4.17–4.11 (m, 1 H), 1.92 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 151.9, 136.4, 133.9, 132.6, 130.9, 129.8, 129.2, 129.1,
128.9, 128.5, 128.2, 128.0, 127.9, 126.9, 126.6, 125.8, 121.9, 117.9,
116.6, 114.6, 29.7, 18.6 ppm. IR (KBr): 3340, 3243, 2952, 2197,
1711, 1656, 1558, 1470, 762 cm–1. HRMS (ESI): calcd. for
C27H20BrN3O3 + Na 536.0581; found 536.0580. [α]2D5 = +9.3 (c =
0.42, CH2Cl2), 82% ee; the enantiomeric ratio was determined by
HPLC on Chiralpak OD column (10% 2-propanol/hexane, 1 mL/
min), tmajor = 8.79 min, tminor = 10.61 min.
(6S,6aR,10aR)-7-Imino-10-methyl-6a-nitro-6-phenyl-9-(p-tolyl)-
6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-8-carbonitrile (5ab):
1
16.2 mg, 36% yield. H NMR (400 MHz, CDCl3): δ = 10.76 (s, 1
H), 7.36–7.33 (m, 10 H), 7.10–7.05 (m, 3 H), 6.10 (s, 1 H), 4.23 (d,
J = 5.8 Hz, 1 H), 3.55–3.51 (m, 1 H), 2.44 (s, 3 H), 1.21 (d, J =
7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.4, 160.3,
153.1, 141.6, 133.2, 130.0, 130.0, 129.2, 129.1, 128.3, 128.1, 128.0,
127.0, 122.0, 117.9, 90.3, 41.4, 29.7, 21.5, 21.3, 18.8 ppm. IR (KBr):
3351, 3255, 2963, 2206, 1715, 1664, 1545, 1471 cm–1. HRMS (ESI):
(6S,6aR,10aR)-2-Chloro-7-imino-10-methyl-6a-nitro-6,9-diphenyl-
6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-8-carbonitrile (5ha):
calcd. for C28H23N3O3 + Na 472.1633; found 472.1632. [α]2D5
=
1
+11.3 (c = 0.22, CH2Cl2), 89% ee; the enantiomeric ratio was deter-
mined by HPLC on Chiralpak IC column (30% 2-propanol/hex-
ane, 1 mL/min), tminor = 11.49 min, tmajor = 14.27 min.
11.8 mg, 23% yield. H NMR (400 MHz, CDCl3): δ = 10.82 (s, 1
H), 7.53–7.52 (m, 2 H), 7.42–7.34 (m, 8 H), 7.31–7.30 (m, 2 H),
6.96 (d, J = 8.6 Hz, 1 H), 6.07 (s, 1 H), 4.18 (d, J = 5.9 Hz, 1
H), 3.49–3.42 (m, 1 H), 1.19 (d, J = 7.2 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 165.7, 159.6, 152.1, 133.0, 131.0, 129.3,
129.2, 128.1, 128.0, 127.8, 126.9, 119.7, 114.1, 89.7, 42.9, 41.4,
18.6 ppm. IR (KBr): 3345, 3247, 2954, 2199, 1715, 1660, 1562,
1473, 765 cm–1. HRMS (ESI): calcd. for C27H20BrN3NaO3
536.0581; found 536.0585. [α]2D5 = +24.9 (c = 0.39, CH2Cl2), 81%
ee; the enantiomeric ratio was determined by HPLC on Chiralpak
IC column (30% 2-propanol/hexane, 1 mL/min), tminor = 9.69 min,
tmajor = 11.75 min.
(6S,6aR,10aR)-7-Amino-2-chloro-9-(4-chlorophenyl)-10-methyl-
6a-nitro-6-(p-tolyl)-6a,10a-dihydro-6H-benzo[c]chromene-8-carbo-
nitrile (4gc): 22.2 mg, 43% yield. 1H NMR (400 MHz, CDCl3): δ
= 7.37–7.34 (m, 2 H), 7.29–7.26 (m, 1 H), 7.19–6.92 (m, 8 H), 5.89
(s, 1 H), 5.26 (s, 2 H), 4.13–4.04 (m, 1 H), 2.34 (s, 3 H), 1.93 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 150.4, 131.8, 130.7,
130.6, 130.2, 130.1, 129.8, 129.6, 128.9, 128.8, 127.1, 127.1, 29.7,
21.2 ppm. IR (KBr): 3351, 3249, 2955, 2186, 1709, 1656, 1564,
1471 cm–1. HRMS (ESI): calcd. for C28H21Cl2N3O3 + Na
540.0855; found 540.0853. [α]2D5 = +9.5 (c = 0.43, CH2Cl2), 86% ee;
the enantiomeric ratio was determined by HPLC on Chiralpak OD
column (10 % 2-propanol/hexane, 1 mL/min), tmajor = 6.99 min,
tminor = 8.09 min.
(6S,6aR,10aR)-7-Amino-3-methoxy-10-methyl-6a-nitro-6,9-di-
phenyl-6a,10a-dihydro-6H-benzo[c]chromene-8-carbonitrile (4ia):
20.0 mg, 43% yield. 1H NMR (400 MHz, CDCl3): δ = 7.40–7.32
(m, 7 H), 7.19–7.14 (m, 4 H), 6.65–6.63 (m, 1 H), 6.54 (d, J =
2.5 Hz, 1 H), 5.91 (s, 1 H), 5.10 (s, 2 H), 4.15–4.10 (m, 1 H), 3.83
(s, 3 H), 1.91 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
160.7, 153.6, 134.3, 129.7, 129.2, 128.8, 128.5, 128.0, 127.1, 109.4,
55.4, 29.7 ppm. IR (KBr): 3349, 3253, 2962, 2205, 1713, 1656, 1567,
1479 cm–1. HRMS (ESI): calcd. for C28H23N3O4 + Na 488.1579;
found 488.1581. [α]2D5 = +7.1 (c = 0.17, CH2Cl2), 91% ee; the enan-
tiomeric ratio was determined by HPLC on Chiralpak OD column
(6S,6aR,10aR)-2-Chloro-9-(4-chlorophenyl)-7-imino-10-methyl-
6a-nitro-6-(p-tolyl)-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-
8-carbonitrile (5gc): 12.9 mg, 25 % yield. 1H NMR (400 MHz,
CDCl3): δ = 10.69 (s, 1 H), 7.54–7.52 (m, 2 H), 7.44–7.39 (m, 2 H),
7.26–7.13 (m, 6 H), 7.02–6.99 (m, 1 H), 6.04 (s, 1 H), 4.14 (d, J =
6.7 Hz, 1 H), 3.52–3.49 (m, 1 H), 2.34 (s, 3 H), 1.20 (d, J = 7.2 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.3, 160.0, 151.5,
138.9, 130.9, 129.2, 129.0, 128.6, 128.6, 127.9, 127.9, 127.0, 126.9,
119.1, 91.9, 89.9, 42.5, 41.8, 21.2, 18.4 ppm. IR (KBr): 3351, 3249,
2961, 2203, 1709, 1658, 1549, 1469, 771 cm–1. HRMS (ESI): calcd.
for C28H21Cl2N3O3 + Na 540.0852; found 540.0851. [α]2D5 = +32.2
(c = 0.18, CH2Cl2), 88% ee; the enantiomeric ratio was determined
by HPLC on Chiralpak IC column (30% 2-propanol/hexane, 1 mL/
min), tminor = 8.04 min, tmajor = 9.00 min.
(10 % 2-propanol/hexane, 1 mL/min), tmajor = 9.56 min, tminor
=
12.72 min.
(6S,6aR,10aR)-7-Imino-3-methoxy-10-methyl-6a-nitro-6,9-diphen-
yl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-8-carbonitrile (5ia):
1
14.0 mg, 30% yield. H NMR (400 MHz, CDCl3): δ = 10.83 (s, 1
H), 7.52–7.51 (m, 3 H), 7.39–7.31 (m, 7 H), 7.21–7.19 (m, 1 H),
6.63–6.59 (m, 2 H), 6.11 (s, 1 H), 4.17 (d, J = 5.5 Hz, 1 H), 3.80
(s, 3 H), 3.54–3.47 (m, 1 H), 1.17 (d, J = 7.2 Hz, 3 H) ppm. 13C (6S,6aR,10aR)-7-Amino-9-(4-chlorophenyl)-10-methyl-6a-nitro-6-
NMR (100 MHz, CDCl3): δ = 166.2, 160.9, 159.9, 154.0, 130.9,
129.2, 129.1, 128.1, 128.0, 127.9, 127.0, 113.7, 110.9, 109.4, 102.1,
90.0, 55.5, 41.6, 29.7, 18.6 ppm. IR (KBr): 3348, 3248, 2956, 2198,
phenyl-6a,10a-dihydro-6H-benzo[c]chromene-8-carbonitrile (4ac):
21.6 mg, 46% yield. 1H NMR (400 MHz, CDCl3): δ = 7.38–7.32
(m, 7 H), 7.19–7.03 (m, 6 H), 6.00 (s, 1 H), 5.43 (s, 2 H), 4.17–4.13
Eur. J. Org. Chem. 2012, 6924–6932
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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