10
Tetrahedron
7a), 2.82 (1H, dd, J 7a,8B = 5.0 Hz, J 8A,8B = 15.1 Hz, H-8B),
70 eV) 309 (27) [M-44]+, 294 (100), 173 (18), 159 (9), 145 (10),
ACCEPTED MANUSCRIPT
2.74 (1H, dd, J 4a,4 = 5.5 Hz, J 4a,7a = 12.8 Hz, H-4a), 2.51 (1H, dd,
131 (9), 118 (10), 107 (10), 91 (47), 77 (9), 59 (15), 42 (23).
J
7a,8A = 11.4 Hz, J 8A,8B = 15.1 Hz, H-8A), 2.19 (3H, s, CH3); 13
C
(4RS,4aRS,7aRS)-6-Benzyl-2-ethyl-5-oxo-4a,5,6,7,7a,8-
hexahydro-4H-furo[2,3-f]isoindole-4-carboxylic acid (14.20).
Yield: 74%; colorless plates; mp 219–221 °C (EtOAc); [Found:
C, 70.62; H, 6.15; N, 4.29. C20H21NO4 requires C, 70.78; H, 6.24;
NMR (100 MHz, DMSO-d6) δ (ppm) 172.5, 172.3 (CO2, C-5),
150.7, 148.9 (C-2, C-8a), 139.8 (C-1 C6H5), 128.7 (2C, C-3, C-5
C6H5), 123.6 (C-4 C6H5), 118.9 (2C, C-2, C-6 C6H5), 116.2 (C-
3a), 106.5 (C-3), 51.1 (C-7), 47.6 (C-4a), 36.8 (C-4), 32.1 (C-7a),
26.4 (C-8), 13.3 (CH3); m/z (APCI) = 312.2 [M+ H]+.
N, 4.13]; IR (KBr) 1731 (CO2H), 1643 (N-C=O) cm-1; H NMR
1
(600 MHz, DMSO-d6) δ (ppm) 12.38 (1H, br. s, CO2H), 7.32–
7.22 (5H, m, C6H5), 6.00 (1H, s, H-3), 4.42 (1H, d, J A,B = 15.1
Hz, NCH2), 4.33 (1H, d, J A,B = 15.1 Hz, NCH2), 3.61 (1H, dd, J
4,7a = 1.4 Hz, J 4a,4 = 5.5 Hz, H-4), 3.32 (1H, dd, J 7a,7B = 6.9 Hz, J
7A,7B = 8.9 Hz, H-7B), 3.05 (1H, dd, J 7a,7A = 10.3 Hz, J 7A,7B = 8.9
Hz, H-7A), 3.00–2.92 (1H, m, H-7a), 2.69 (1H, dd, J 7a,8B = 4.8
Hz, J 8A,8B = 15.1 Hz, H-8B), 2.53–2.42 (4H, m, CH2, H-4a, H-
8A), 1.18 (3H, t, J = 7.6 Hz, CH3); 13C NMR (151 MHz, DMSO-
d6) δ (ppm) 173.14, 173.11 (CO2, C-5), 156.6, 149.6 (C-2, C-8a),
137.7 (C-1 C6H5), 129.1 (2C, C-2, C-6 C6H5), 128.0 (2C, C-3, C-
5 C6H5), 127.7 (C-4 C6H5), 116.6 (C-3a), 105.6 (C-3), 50.0, 46.7,
45.9 (C-4a, C-7, NCH2), 37.2 (C-4), 33.6 (C-7a), 26.9 (C-8), 21.4
(CH2), 12.6 (CH3); m/z (EI, 70 eV) 295 (98) [M-44]+, 278 (15),
238 (9), 204 (9), 161 (10), 122 (15), 91 (100), 65 (13), 55 (11),
42 (17).
(4RS,4aRS,7aSR)-6-Benzyl-2,4-dimethyl-5-oxo-4a,5,6,7,7a,8-
hexahydro-4H-furo[2,3-f]isoindole-4-carboxylic acid (14.17).
Yield: 49%; white powder; mp 226–228 °C (EtOAc–EtOH);
[Found: C, 70.63; H, 6.10; N, 3.89. C20H21NO4 requires C, 70.78;
H, 6.24; N, 4.13]; IR (KBr) 1726 (CO2H), 1646 (N-C=O) cm-1;
1H NMR (600 MHz, DMSO-d6) δ (ppm) 12.37 (1H, br. s, CO2H),
7.33–7.22 (5H, m, C6H5), 6.03 (1H, s, H-3), 4.42 (1H, d, J
=
A,B
14.9 Hz, NCH2), 4.29 (1H, d, J A,B = 14.9 Hz, NCH2), 3.29 (1H,
dd, J 7a,7B = 7.4 Hz, J 7A,7B = 9.1 Hz, H-7B), 3.00 (1H, dd, J 7A,7B
9.1 Hz, J = 9.9 Hz, H-7A), 2.96-2.88 (1H, m, H-7a), 2.66
=
7a,7A
(1H, dd, J 7a,8B = 4.9 Hz, J 8A,8B = 15.7 Hz, H-8B), 2.42 (1H, dd, J
= 11.6 Hz, J = 15.7 Hz, H-8A), 2.23 (1H, d, J
=
4a,7a
7a,8A
8A,8B
12.4 Hz, H-4a), 2.16 (3H, s, CH3), 1.57 (3H, s, CH3); 13C NMR
(151 MHz, DMSO-d6) δ (ppm) 175.1, 173.2 (CO2, C-5), 151.0,
148.7 (C-2, C-8a), 137.8 (C-1 C6H5), 129.0 (2C, C6H5), 128.0
(2C, C6H5), 127.7 (C-4 C6H5), 123.4 (C-3a), 105.6 (C-3), 52.7,
49.5, 45.7, 42.3 (C-4, C-4а, C-7, NCH2), 34.7 (C-7a), 26.9 (C-8),
24.7 (CH3), 13.9 (CH3); m/z (EI, 70 eV) 295 (100) [M-44]+, 280
(24), 278 (18), 252 (8), 204 (9), 174 (11), 147 (17), 133 (14), 122
(24), 119 (19), 105 (17), 95 (13), 91 (89), 90 (41), 65 (16).
(4RS,4aRS,7aSR)-6-Benzyl-2-ethyl-4-methyl-5-oxo-
4a,5,6,7,7a,8-hexahydro-4H-furo[2,3-f]isoindole-4-carboxylic
acid (14.21). Yield: 53%; colorless dendrites; mp 221–224 °C
(EtOAc); [Found: C, 71.44; H, 6.55; N, 3.82. C21H23NO4 requires
C, 71.37; H, 6.56; N, 3.96]; IR (KBr) 1723 (CO2H), 1629 (N-
1
C=O) cm-1; H NMR (600 MHz, DMSO-d6) δ (ppm) 12.37 (1H,
(4RS,4aRS,7aSR)-2,4-Dimethyl-5-oxo-6-phenyl-4a,5,6,7,7a,8-
hexahydro-4H-furo[2,3-f]isoindole-4-carboxylic acid (14.18).
Yield: 64%; thin transparent needles; mp 220 °C (EtOH);
[Found: C, 70.31; H, 6.08; N, 4.50. C19H19NO4 requires C, 70.14;
H, 5.89; N, 4.31]; IR (KBr) 1730 (CO2H), 1655 (N-C=O) cm-1;
1H NMR (600 MHz, DMSO-d6) δ (ppm) 12.40 (1H, s, CO2H),
7.61 (2H, d, J 2(6),3(5) = 8.2 Hz, H-2 and H-6 C6H5), 7.31 (2H, br. t,
br. s, CO2H), 7.32–7.21 (5H, m, H C6H5), 6.03 (1H, s, H-3), 4.43
(1H, d, J
= 15.1 Hz, NCH2), 4.29 (1H, d, J
= 15.1 Hz,
A,B
A,B
NCH2A), 3.29 (1H, dd, J
= 6.9 Hz, J
= 8.2 Hz, H-7B),
7a,7B
7A,7B
3.00 (1H, dd, J 7A,7B = 8.2 Hz, J 7a,7A = 10.3 Hz, H-7A), 2.97−2.90
(1H, m, H-7a), 2.66 (1H, dd, J 7a,8B = 4.8 Hz, J 8A,8B = 15.1 Hz, H-
8B), 2.50 (2H, q, J = 7.6 Hz, CH2), 2.42 (1H, dd, J
= 11.0
7a,8A
Hz, J 8A,8B = 15.1 Hz, H-8A), 2.23 (1H d, J 4a,7a = 12.0 Hz, H-4a),
1.60 (3H, s, CH3), 1.09 (3H, t, J = 7.6 Hz, CH3); 13C NMR (151
MHz, DMSO-d6) δ (ppm) 175.1, 173.2 (CO2, C-5), 156.6, 148.7
(C-2, C-8a), 137.8 (C-1 C6H5), 129.0 (2C, C6H5), 128.0 (2C,
C6H5), 127.7 (C-4 C6H5), 123.2 (C-3a), 104.1 (C-3), 52.7, 49.5,
45.8, 42.4 (C-4, C-4а, C-7, NCH2), 34.7 (C-7a), 27.0 (C-8), 24.7
(CH3), 21.4 (CH2), 12.6 (CH2-CH3); m/z (EI, 70 eV) 309 (100)
[M-44]+, 294 (48), 252 (10), 173 (8), 161 (12), 133 (13), 111
(18), 91 (86), 58 (34), 42 (64), 33 (74).
J 3(5),2(6) = J 3(5),4 = 8.2 Hz, H-3 and H-5 C6H5), 7.06 (1H, t, J 4,3(5)
=
8.2 Hz, H-4 C6H5), 6.03 (1H, s, H-3), 3.87 (1H, dd, J 7a,7B = 7.6
Hz, J 7A,7B = 8.9 Hz, H-7B), 3.58 (1H, dd, J 7A,7B = 8.9 Hz, J 7a,7A
10.3 Hz, H-7A), 3.04–2.96 (1H, m, H-7a), 2.77 (1H, dd, J 7a,8B
=
=
4.8 Hz, J 8A,8B = 15.1 Hz, H-8B), 2.54 (1H, dd, J 7a,8A = 11.7 Hz, J
8A,8B = 15.1 Hz, H-8A), 2.47 (1H, d, J 4a,7a = 13.1 Hz, H-4a), 2.16
(3H, s, CH3), 1.57 (3H, s, CH3); 13C NMR (100 MHz, DMSO-d6)
δ (ppm) 175.1, 173.0 (CO2, C-5), 151.2, 148.4 (C-2, C-8a), 140.4
(C-1 C6H5), 129.2 (2С, C-3, C-5 C6H5), 124.1 (C-4 C6H5), 123.4
(C-3a), 119.5 (2C, C-2, C-6 C6H5), 105.6 (C-3), 53.9, 51.1 (C-4a,
C-7), 42.6 (C-4), 33.7 (C-7a), 26.9 (C-8), 24.7 (CH3), 13.9 (CH3);
m/z (APCI) 326.1 [M + H]+.
(4RS,4aRS,7aSR)-6-Benzyl-5-oxo-2-propyl-4a,5,6,7,7a,8-
hexahydro-4H-furo[2,3-f]isoindole-4-carboxylic acid (14.22).
Yield: 27%; white powder; mp 203–205 °C (EtOAc/EtOH);
[Found: C, 71.24; H, 6.31; N, 4.00. C21H23NO4 requires C, 71.37;
H, 6.56; N, 3.96]; IR (KBr) 1731 (CO2H), 1640 (N-C=O) cm-1;
1H NMR (600 MHz, DMSO-d6) δ (ppm) 12.36 (1H, br. s, CO2H),
(4RS,4aSR,7aRS)-6-Benzyl-2,4,4a-trimethyl-5-oxo-
4a,5,6,7,7a,8-hexahydro-4H-furo[2,3-f]isoindole-4-carboxylic
acid (14.19). Yield: 51%; colorless prisms; mp 227–229 °C
(EtOAc–EtOH); [Found: C, 71.21; H, 6.72; N, 4.12. C21H23NO4
requires C, 71.37; H, 6.56; N, 3.96]; IR (KBr) 1730 (CO2H),
1626 (N-C=O) cm-1; 1H NMR (600 MHz, CDCl3) δ (ppm)
7.33−7.26 (5H, m, C6H5), 6.03 (1H, d, J 3,CH3 = 1.0 Hz, H-3), 4.56
7.31–7.22 (5H, m, C6H5), 6.00 (1H, s, H-3), 4.42 (1H, d, J A,B
=
15.1 Hz, NCH2), 4.33 (1H, d, J A,B = 15.1 Hz, NCH2), 3.61 (1H,
dd, J 4,7a = 2.1 Hz, J 4a,4 = 5.5 Hz, H-4), 3.31 (1H, dd, J 7a,7B = 7.6
Hz, J 7A,7B = 8.9 Hz, H-7B), 3.05 (1H, dd, J 7a,7A = 10.3 Hz, J 7A,7B
= 8.9 Hz, H-7A), 3.00–2.92 (1H, m, H-7a), 2.69 (1H, dd, J 7a,8B
=
(1H, d, J
= 14.8 Hz, NCH2), 4.34 (1H, d, J
= 14.8 Hz,
4.8 Hz, J 8A,8B = 15.1 Hz, H-8B), 2.50 (1H, dd, J 4,4a = 5.5 Hz, J
A,B
A,B
NCH2), 3.23 (1H, dd, J 7a,7B = 6.2 Hz, J
= 7.9 Hz, H-7B),
= 13.1 Hz, H-4a), 2.48–2.46 (2H, m, CH2), 2.43 (1H, dd, J
7A,7B
4a,7a
3.06−3.01 (2H, m, H-7a, H-7A), 2.58 (1H, dd, J 7a,8B = 4.5 Hz, J
= 15.5 Hz, H-8B), 2.37 (1H, dd, J 7a,8A = 11.3 Hz, J
= 11.0 Hz, J
= 15.1 Hz, H-8A), 1.52 (2H, seq, J = 7.6
7a,8A
8A,8B
=
8A,8B
Hz, CH2), 0.86 (3H, t, J = 7.6 Hz, CH3); 13C NMR (151 MHz,
DMSO-d6) δ (ppm) 173.17, 173.11 (CO2, C-5), 155.2, 149.7 (C-
2, C-8a), 137.7 (C-1 C6H5), 129.1 (2C, C6H5), 128.0 (2C, C6H5),
127.7 (C-4 C6H5), 116.6 (C-3a), 106.3 (C-3), 50.0, 46.7, 45.9 (C-
4a, C-7, NCH2), 37.2 (C-4), 33.7 (C-7a), 30.0 (CH2), 26.9 (C-8),
21.4 (CH2), 14.2 (CH3); m/z (EI, 70 eV) 309 (55) [M-44]+, 280
8A,8B
15.5 Hz, H-8A), 2.23 (3H, s, CH3), 1.77 (3H, s, CH3), 1.01 (3H,
s, CH3); 13C NMR (151 MHz, CDCl3) δ (ppm) 179.5, 178.1
(CO2, C-5), 151.5 (C-8a), 147.3 (C-2), 137.0 (C-1 C6H5), 128.7
(2C, C6H5), 128.1 (2C, C6H5), 127.5 (C-4 C6H5), 121.5 (C-3a),
105.9 (C-3), 47.9, 47.4, 47.2, 46.3 (C-4, C-4a, C-7, NCH2), 36.8
(C-7a), 22.8 (C-8), 18.9 (CH3), 13.8 (CH3), 11.7 (CH3); m/z (EI,