Naffziger et al.
7.02 (m, 2H), 6.83 (d, J ) 8.4 Hz, 1H), 6.40 (d, J ) 2.4 Hz, 1H),
6.39 (dd, J ) 8.4, 2.4 Hz, 1H), 4.99 (d, J ) 12.4, 1H), 4.87 (d, J
) 12.4, 1H), 3.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.7,
156.8, 151.2, 144.6, 140.1, 137.0, 133.9, 131.5, 131.1, 129.2, 128.4,
127.8, 127.7, 127.6, 127.0, 126.7, 122.5, 117.5, 104.8, 99.9, 70.0,
55.2; HRMS (FAB+) calcd for C26H21NO4 (M+) 411.1471, found
411.1462.
5.12 (s, 2H), 3.88 (s, 3H), 3.85 (broad s, 2H); 13C NMR (75 MHz,
CDCl3) δ 160.5, 156.9, 142.0, 140.2, 137.2, 132.4, 130.7, 129.5,
129.4, 128.8, 128.5, 127.8, 127.7, 127.1, 126.9, 125.0, 122.0, 117.9,
106.0, 101.3, 70.7, 55.5; HRMS (EI+) calcd for C26H23NO2 (M +
H) 382.1729, found 381.1728.
Representative Procedure for Hydrogenation with Pd/C. To
a stirred solution of benzylated nitro arene 34 or 37 (0.1 mmol)
and EtOH (0.28 M, absolute) was added Pd/C (475 mg/mmol, 10%
Pd). After being stirred under an atmosphere of H2 for 21 h, the
mixture was filtered over a pad of Celite with EtOAc and
concentrated in vacuo. The product was purified via flash chro-
matography over silica gel, eluting with 15-20% EtOAc/hexanes
to give the anilino phenol 60 or 61 (67-85%).
Representative Procedure for Palladium Couplings with (t-
Bu3P)2Pd: Synthesis of Triaryl 37. To a pressure vessel containing
30 (552 mg, 1.49 mmol) was sequentially added KF (783 mg, 13.5
mmol), C6H5-B(OH)2 (732 mg, 6.00 mmol), (t-Bu3P)2Pd (38.4 mg,
0.0750 mmol), and NMP (15.0 mL). The solution was sealed under
Ar and heated to 80 °C. After 48 h, the reaction was quenched
with saturated aq NH4Cl (15 mL), diluted with EtOAc (100 mL),
and washed with H2O (50 mL) and saturated aq NaCl (50 mL).
The dried extract (MgSO4) was concentrated in vacuo and purified
by chromatography over silica gel, eluting with 5-25% EtOAc/
hexanes to give 37 (582 mg, 1.42 mmol, 95%) as a yellow
crystalline solid. Mp 107-108 °C; IR (neat) 3063, 2930, 1608,
60 (67%): IR (neat) 3472, 3382, 3187, 3057, 2959, 1621, 1573,
1
1265, 1161, 1039 cm-1; H NMR (400 MHz, CDCl3) δ 7.30 (t, J
) 7.9 Hz, 1H), 7.25-7.10 (m, 5H), 6.95 (dd, J ) 7.6, 1.0 Hz,
1H), 6.86 (dd, J ) 8.0, 1.0 Hz, 1H), 6.80 (d, J ) 8.5 Hz, 1H), 6.54
(d, J ) 2.5 Hz, 1H), 6.38 (dd, 8.5, 2.5 Hz, 1H), 3.78 (s, 3H), 4.70-
3.40 (br, 3H); 13C NMR (100 MHz, CDCl3) δ 160.7, 154.7, 144.7,
144.0, 141.3, 132.6, 129.1, 129.1, 127.7, 126.5, 121.4, 120.6, 115.9,
114.9, 107.3, 101.6, 55.2; HRMS (EI+) calcd for C19H17NO2
291.1259, found 291.1251.
1
1534 cm-1; H NMR (400 MHz, CDCl3) δ 7.57 (t, J ) 7.6 Hz,
1H), 7.46-7.42 (m, 7H), 7.37-7.30 (m, 5H), 7.22 (d, J ) 8.0 Hz,
1H), 6.60-6.57 (m, 2H), 5.08 (s, 2H), 3.82 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 161.2, 156.9, 150.4, 137.2, 137.0, 134.6, 131.8,
131.6, 130.9, 129.9, 129.7, 128.7, 128.5, 128.3, 128.1, 127.7, 126.8,
118.6, 105.3, 100.7, 70.5, 55.4; HRMS (FAB+) calcd for C26H21-
NO4 (M + H) 411.1471, found 411.1491.
Phenol 61: mp 87-89 °C; IR (neat) 3394, 3301, 2921, 1731,
1
1617, 1160 cm-1; H NMR (400 MHz, CDCl3) δ 7.55-7.50 (m,
4H), 7.45 (m, 1H), 7.29 (d, J ) 2.0 Hz, 1H), 7.26 (dd, J ) 1.6, 7.6
Hz, 1H), 7.23 (dd, J ) 1.6, 8.4 Hz, 1H), 7.05 (t, J ) 7.6 Hz, 1H),
6.69 (m, 2H), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.1,
154.9, 139.0, 138.9, 131.9, 131.1, 129.9, 129.8, 129.3, 129.1, 127.7,
126.3, 120.6, 118.8, 107.9, 103.1 55.4; HRMS (EI+) calcd for
C19H17NO2 (M + H) 291.1259, found 291.126.
Representative Procedure for Debenzylation with BCl3. To
a stirred solution of benzyl ether 34 or 37 (0.1 mmol) in CH2Cl2
(1.2 M) was added BCl3 (5.45 equiv, 1.0 M in heptane) at 0 °C.
After 4 h, the reaction was quenched with MeOH, concentrated in
vacuo, and purified via flash chromatography over silica gel, eluting
with 10-30% EtOAc/hexanes to give the phenol 56 or 57 (82-
92%).
Representative Procedure Cadogan Cyclization with PPh3.
To a pressure vessel containing 20, 21, 22, or 32 (0.1 mmol) and
o-C6H4Cl2 (0.5 M) was added PPh3 (2.5 equiv) at rt. The mixture
was heated to 180 °C. After 24 h, the reaction was cooled to rt and
purified via flash chromatography over silica gel, eluting with 10-
30% EtOAc/hexanes, and recrystalization affored the carbazole 62,
63, 64, or 65 (65-89%) as an off-white solid.
56 (92%): IR (neat) 3522, 1620, 1592, 1526, 1360, 1264, 1040,
1
877, 764 cm-1; H NMR (400 MHz, CDCl3) δ 7.85 (dd, J ) 8.0,
1.4 Hz, 1H), 7.68 (dd, J ) 8.0,1.4 Hz, 1H), 7.60 (t, J ) 8.0 Hz,
1H), 7.28-7.21 (m, 3H), 7.19-7.12 (m, 2H), 6.77(d, J ) 8.0 Hz,
1H), 6.41-6.32 (m, 2H), 4.95 (br, 1H), 3.65 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 160.8, 154.0, 151.7, 145.2, 139.5, 134.1,
131.5, 129.7, 129.1, 128.5, 128.0, 127.4, 122.6, 115.0, 106.7, 101.7,
55.2; HRMS (EI+) calcd for C19H15NO4 321.1001, found 321.0999.
57 (82%): mp 166-167 °C; IR (neat) 3409, 2921, 1617, 1530
62 (75%): mp 158-160 °C; IR (thin film) 3387, 1177 cm-1
;
1H NMR (400 MHz, CDCl3) δ 8.48 (d, J ) 8.7 Hz, 1H), 8.02 (br
s, 1H), 7.52 (d, J) 7.2 Hz, 2H), 7.45 (t, J ) 7.2 Hz, 2H), 7.38 (t,
J ) 7.2 Hz, 1H), 7.33-7.18 (m, 3 H), 7.03 (dd, J ) 8.7, 2.2 Hz,
1H), 6.97 (d, J ) 0.9 Hz, 1H), 5.19 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 158.5, 140.8, 140.6, 137.0, 128.7, 128.0, 127.8, 127.5,
125.0, 123.9, 120.9, 120.3, 116.4, 109.3, 108.6, 95.7, 70.4; HRMS
(EI+) calcd for C19H14NOCl (M+) 307.0764, found 307.0775.
63 (89%): mp 222-224 °C°C; IR (KBr) 3390, 2916, 1624, 1225,
1
cm-1; H NMR (400 MHz, MeOD) δ 7.62 (t, J ) 7.7 Hz, 1H),
7.46-7.38 (m, 7H), 7.05 (d, J ) 8.0 Hz, 1H), 6.50-6.47 (m, 2H),
3.81 (s, 3H); 13C NMR (100 MHz, MeOD) δ 161.3, 155.6, 152.8,
150.5, 137.4, 134.4, 132.0, 131.5, 130.5, 129.5, 128.2, 127.9, 127.8,
116.6, 104.7, 101.0, 54.3; HRMS (EI+) calcd for C19H15NO4 (M
+ H) 321.1001, found 321.1004.
1
1176, 1027, 816, 728 cm-1; H NMR (400 MHz, d6-DMSO) δ
11.30 (s, 1H), 8.11 (s, 1H), 8.04 (d, J ) 7.8 Hz, 1H), 7.68-7.19
(m, 7H), 7.08 (s, 1H), 6.89 (d, J ) 7.8 Hz, 1H), 5.22 (s, 2H); 13C
NMR (100 MHz, d6-DMSO) δ 158.5, 142.2, 138.7, 137.7, 128.9,
128.3, 128.2, 124.5, 124.3, 123.4, 122.0, 119.4, 116.0, 112.5, 109.4,
96.2, 70.0; HRMS (EI+) calcd for C19H14NOCl (M+) 307.0764,
found 307.0764.
Representative Procedure for Nitro Reduction with Zn/
HOAc. To a stirred solution of nitroarene 34 or 37 (0.1 mmol) in
glacial HOAc (0.25 M) was added Zn dust (6.3 equiv) at rt. After
20 h, the mixture was quenched with saturated aq NaHCO3, diluted
with EtOAc, and washed with H2O and saturated aq NaCl. The
dried extract (Na2SO4) was concentrated in vacuo and purified via
flash chromatography over silica gel, eluting with 15-25% EtOAc/
hexanes to give the aniline 58 or 59 (90-97%).
64 (84%): mp 235-238 °C; IR (KBr) 3396, 2923, 1605, 1016,
1
797 cm-1; H NMR (400 MHz, d6-DMSO) δ 11.29 (s, 1H), 8.02
(d, J ) 3.3 Hz, 1H), 8.00 (d, J ) 3.7 Hz, 1H), 7.52 (d, J ) 7.2 Hz,
2H), 7.46 (d, J ) 1.8 Hz, 1H), 7.43 (t, J ) 7.1 Hz, 2H), 7.35 (t, J
) 7.3 Hz, 1H), 7.14 (dd, J ) 8.3, 1.9 Hz, 1H), 7.09 (d, J ) 2.3
Hz, 1H), 6.90 (dd, J ) 8.6, 2.3 Hz, 1H), 5.21 (s, 2H); 13C NMR
(100 MHz, d6-DMSO) δ 158.3, 141.9, 140.9, 137.7, 129.0, 128.9,
128.3, 128.2, 122.0, 121.6, 121.1, 119.1, 116.2, 110.8, 109.4, 96.4,
70.0; HRMS (EI+) calcd for C19H14NOCl (M+) 307.0764, found
307.0772.
58 (90%): IR (neat) 3471, 3379, 3058, 2835, 1609, 1580, 1266,
1
1044 cm-1; H NMR (400 MHz, CDCl3) δ 7.38-7.13 (m, 11H),
7.01 (d, J ) 9.0 Hz, 1H), 6.87 (dd, J ) 8.0,1.1 Hz, 1H), 6.83 (dd,
J ) 8.0, 1.1 H, 1H), 6.54-6.41 (m, 2H), 5.02 (d, J ) 12.8 Hz,
1H), 4.92 (d, J ) 12.8 Hz, 1H), 3.76 (s, 3H), 3.52 (br, 2H); 13C
NMR (100 MHz, CDCl3) δ 160.2, 157.2, 145.0, 143.2, 142.4, 137.4,
132.9, 129.3, 128.4, 128.1, 127.5, 127.4, 126.6, 126.0, 122.9, 120.2,
119.4, 114.3, 105.4, 100.6, 69.9, 55.3; HRMS (EI+) calcd for
C26H23NO2 381.1729, found 381.1721.
65 (65%): mp 145-146 °C; IR 3419, 2911, 1419, 735; 1H NMR
(400 MHz, CDCl3) δ 8.21 (br s, 1H), 7.96 (d, J ) 8.6 Hz, 1H),
7.89 (d, J ) 7.8 Hz, 1H), 7.52 (d, J ) 7.2 Hz, 2H), 7.45 (t, J )
7.1, 7.6 Hz, 2H), 7.38 (t, J ) 7.2, 7.8 Hz, 2 H), 7.18 (t, J ) 7.8
Hz, 1H), 7.07 (d, J ) 2.0 Hz, 1H), 7.00 (dd, J ) 2.2 Hz, 8.6 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 158.7, 140.5, 137.0, 136.7,
59 (97%): IR (neat) 3471, 3385, 3057, 2933, 1611, 1503, 1163
1
cm-1; H NMR (300 MHz, CDCl3) δ 7.56-7.48 (m, 4H), 7.41
(dt, J ) 1.5, 1.5, 7.2 Hz, 1H), 7.38-7.32 (m, 6H), 7.20 (dd, J )
1.2, 7.2 Hz, 2H), 6.93 (t, J ) 7.5 Hz, 1H), 6.71-6.67 (m, 2H),
9864 J. Org. Chem., Vol. 72, No. 26, 2007