The Journal of Organic Chemistry
Article
Bis(3-methoxyphenyl)amine (8l).19g Following the GP, 3-anisidine
6f (53 mg, 0.43 mmol, 1 equiv) and 3-iodoanisole 7i (151 mg, 0.65
mmol, 1.5 equiv) afforded 8l as a brownish white solid (74 mg, 76%).
1H NMR (400 MHz, CDCl3): 7.16 (t, 2H, J = 8.1 Hz), 6.67−6.64 (m,
4H), 6.48(dd, 2H, J = 6.6, 1.4 Hz), 5.72 (br s, 1H), 3.77 (s, 6H). 13C
NMR (100 MHz, CDCl3): 160.8, 144.4, 130.2, 110.8, 106.6, 103.9,
55.3. HRMS (ESI) calcd for C14H16NO2 [M + H]+: 230.1181, found
230.1147.
125−127 °C. 1H NMR (500 MHz, CDCl3): 7.67 (d, 1H, J = 7.6 Hz),
7.45 (d, 1H, J = 8.2 Hz), 7.40 (dd, 2H, J = 5.7 Hz, 4.0 Hz), 7.27 (d,
1H, J = 6.3 Hz), 7.18 (t, 1H, J = 6.9 Hz), 7.15 (t, 1H, J = 7.0 Hz), 7.03
(dd, 2H, J = 8.2 Hz, 7.0 Hz), 6.64 (d, 2H, J = 7.6 Hz), 3.87 (s, 3H).
13C NMR (100 MHz, CDCl3): 158.4, 136.5, 133.0, 129.1, 128.4, 126.2,
122.3, 121.2, 120.2, 114.9, 110.5, 103.0, 55.7. HRMS (ESI) calcd for
C15H14NO [M + H]+: 224.1075, found 224.1068.
9-(4-Methoxyphenyl)-9H-carbazole (10f).6a Following the GP,
carbazole 9f (84 mg, 0.5 mmol, 1 equiv) and 4-iodoanisole 7a (175
mg, 0. 75 mmol, 1.5 equiv) afforded 10f as a white solid (91.6 mg,
78%). Mp: 155−156 °C. 1H NMR (500 MHz, CDCl3): 8.14 (d, 2H, J
= 7.6 Hz), 7.45 (d, 2H, J = 7.6 Hz), 7.39 (t, 2H, J = 7.6 Hz), 7.32 (d,
2H, J = 8.4 Hz), 7.11 (d, 2H, J = 8.4 Hz), 3.91 (s, 3H). 13C NMR (125
MHz, CDCl3): 159.1, 141.6, 130.5, 128.8, 126.0, 123.3, 120.4, 119.8,
115.3, 109.8, 55.8. HRMS (ESI) calcd for C19H16NO [M + H]+:
274.1232, found 274.1241.
1-(4-((4-Methoxyphenyl)amino)phenyl)ethanone (8m).19h Fol-
lowing the GP, 4-aminoacetophenone 6g (50 mg, 0.4 mmol, 1
equiv) and p-iodoanisole 7a (140 mg, 0.6 mmol, 1.5 equiv) afforded
1
8m as a white solid (28.9 mg, 30%). H NMR (500 MHz, CDCl3):
7.83 (d, 2H, J = 8.4 Hz), 7.14 (d, 2H, J = 8.4 Hz), 6.91(d, 2H, J = 9.2
Hz), 6.81 (d, 2H, J = 8.4 Hz), 5.89 (br s, 1H), 3.82 (s, 3H), 2.51 (s,
3H). 13C NMR (100 MHz, CDCl3): 196.5, 156.9, 150.3, 133.3, 130.9,
128.4, 124.8, 114.9, 113.3, 55.7, 26.2. HRMS (ESI) calcd for
C15H16NO2 [M + H]+: 242.1181, found 242.1179.
3-Methoxy-N-(4-methoxyphenyl)-4-methylaniline (8o). Following
the GP, 2-methoxy-4-methylaniline 6h (100 mg, 0.73 mmol, 1 equiv)
and iodobenzene 7b (0.12 mL, 1.09 mmol, 1.5 equiv) afford 8o as a
white solid (133 mg, 75%). 1H NMR (500 MHz, CDCl3): 7.24 (t, 2H,
J = 8.4 Hz), 7.19 (d, 1H, J = 7.6 Hz), 7.08 (d, 2H, J = 7.6 Hz), 6.89
(dd, 2H, J = 7.6 Hz, 5.9 Hz), 6.70 (t, 2H, J = 6.7 Hz), 5.99 (br s, 2H),
3.86 (s, 3H), 2.31(s, 3H). 13C NMR (125 MHz, CDCl3): 148.9, 143.6,
130.3, 130.2, 129.4, 128.9, 121.5, 121.1, 120.6, 117.8, 116.1, 111.9,
55.7, 21.3. HRMS (ESI) calcd for C14H16NO [M + H]+: 214.1232,
found 214.1236.
N-(4-Methoxyphenyl)benzo[d]thiazol-2-amine (10g).20a Follow-
ing the GP, benzo[d]thiazol-2-amine 9g (50 mg, 0.3 mmol, 1 equiv)
and p-iodoanisole 7a (116 mg, 0.5 mmol, 1.5 equiv) afforded 10g as a
1
white solid (59.6 mg, 70%). Mp: 159−161 °C. H NMR (500 MHz,
CDCl3): 7.39 (d, 1H, J = 7.6 Hz), 7.18 (t, 1H, J = 7.6 Hz), 7.13 (d,
2H, J = 8.4 Hz), 6.80 (d, 2H, J = 8.4 Hz), 6.73 (dd, 2H, J = 10.1, 7.6
Hz), 3.76 (s, 3H). 13C NMR (100 MHz, CDCl3):158.5, 148.2, 136.5,
130.5, 129.8, 127.0, 118.9, 116.9, 115.5, 115.0, 55.5. HRMS (ESI)
calcd for C14H13N2OS [M + H]+: 257.0749, found 257.0738.
4-((4-Methoxyphenyl)amino)pyrimidin-2(1H)-one (10h). Follow-
ing the GP, cytosine 9h (108 mg, 0.5 mmol, 1 equiv) and 4-
iodoanisole 7a (175 mg, 0. 75 mmol, 1.5 equiv) afforded 10h as a
gummy white solid (64 mg, 68%). 1H NMR (500 MHz, CDCl3): 8.37
(br s, 1H), 7.30 (d, 1H, J = 7.6 Hz), 7.25 (d, 2H, J = 7.6 Hz), 6.99 (d,
2H, J = 6.7 Hz), 5.80 (d, 1H, J = 7.6 Hz), 3.85 (s, 3H). 13C NMR (125
MHz, CDCl3): 162.9, 159.8, 150.4, 145.2, 131.4, 127.7, 115.0, 102.5,
55.8. HRMS (ESI) calcd for C11H12N3O2 [M + H]+: 218.0930, found
218.0922.
3,5-Dimethoxy-N-(4-methoxyphenyl)aniline (8p).19i Following
the GP, 3,5-dimethoxyaniline 6i (50 mg, 0.33 mmol, 1 equiv) and
p-iodoanisole 7a (114.6 mg, 0. 49 mmol, 1.5 equiv) afforded 8p as a
brown oil (60 mg, 70%). 1H NMR (400 MHz, CDCl3): 7.08 (d, 2H, J
= 8.8 Hz), 6.85 (d, 2H, J = 8.8 Hz), 6.77 (br s, 1H), 6.06 (d, 2H, J =
1.5 Hz), 5.98 (s, 1H), 3.80 (s, 3H), 3.74 (s, 6H). 13C NMR (100 MHz,
CDCl3): 161.9, 155.8, 147.6, 135.4, 123.3, 116.1, 114.9, 114.8, 94.2,
91.9, 55.7, 55.4. HRMS (ESI) calcd for C15H18NO3 [M + H]+:
260.1287, found 260.1272.
4-(Phenylamino)pyrimidin-2(1H)-one (10i). Following the GP,
cytosine 9h (108 mg, 0.5 mmol, 1 equiv) and iodobenzene 7b (78 μL,
0.75 mmol, 1.5 equiv) afforded 10i as a white solid (61 mg, 66%). Mp:
N-(4-Methoxybenzyl)aniline (10a).19e Following the GP, benzyl-
amine 9a (54 mg, 0.5 mmol, 1 equiv) and 4-iodoanisole 7a (175 mg,
0.75 mmol, 1.5 equiv) afforded 10a as a white solid (73 mg, 79%). 1H
NMR (125 MHz, CDCl3): 7.37−7.31 (m, 4H), 7.25 (dd, 1H, J = 7.4,
7.3 Hz), 6.76 (d, 2H, J = 9.8 Hz), 6.59 (d, 2H, J = 9.2 Hz), 4.27 (s,
2H), 3.73 (s, 3H). 13C NMR (125 MHz, CDCl3): 152.4, 142.6, 139.8,
128.7, 127.7, 127.3, 115.1, 114.3, 55.9, 49.4. HRMS (ESI) calcd for
C14H16NO [M + H]+: 214.1232, found 214.1246.
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238−242 °C. H NMR (500 MHz, CDCl3): 8.51 (br s, 1H), 7.50 (t,
2H, J = 8.4 Hz), 7.45 (d, 2H, J = 7.6 Hz), 7.36−7.33 (m, 3H), 5.82 (d,
1H, J = 8.4 Hz); 13C NMR (125 MHz, CDCl3): 163.2, 150.2, 144.8,
138.5, 129.8, 129.2, 126.4, 102.8. HRMS (ESI) calcd for C10H10N O
3
[M + H]+: 188.0824, found 188.0813.
1-(4-Methoxyphenyl)pyrimidine-2,4(1H,3H)-dione (10j).20b Fol-
lowing the GP, uracil 9i (109 mg, 0.43 mmol, 1 equiv) and 4-
iodoanisole 7a (175 mg, 0. 75 mmol, 1.5 equiv) afforded 10j as a white
solid (62 mg, 66%). Mp: 229−231 °C. 1H NMR (500 MHz): 8.35 (br
s, 1H), 7.29 (d, 1H, J = 7.9 Hz), 7.25−7.23 (m, 2H), 6.98 (d, 2H, J =
8. Hz), 3.84 (3H, s); 13C NMR (125 MHz): 163.2, 159.1, 150.1, 145.2,
1-(4-Methoxyphenyl)piperidine (10b).19f Following the GP,
piperidine 9b (42 mg, 0.5 mmol, 1 equiv) and 4-iodoanisole 7a
(175 mg, 0. 75 mmol, 1.5 equiv) afforded 10b as a yellow oil (55 mg,
67%). 1H NMR (500 MHz, CDCl3): 6.9 (d, 2H, J = 8.8 Hz), 6.82 (d,
2H, J = 8.2 Hz), 3.76 (s, 3H), 3.03 (t, 4H, J = 5.7 Hz); 1.75−1.70 (m,
4H), 1.57−1.53 (m, 2H). 13C NMR (125 MHz, CDCl3): 153.8, 147.1,
118.9, 114.5, 55.7, 52.5, 26.3, 24.3. HRMS (ESI) calcd for C12H18NO
[M + H]+: 192.1388, found 192.1367.
131.3, 127.7, 115.1, 102.5, 55.8. HRMS (ESI) calcd for C11H11N O3
2
[M + H]+: 219.0770, found 219.0794.
N-(4-Methoxyphenyl)pyridin-2-amine (12).20c Following the GP,
p-anisidine 6a (50 mg, 0.4 mmol, 1 equiv) and 2-bromopyridine 11
(156 μL, 0.6 mmol, 1.5 equiv) afforded 12 as a white solid (56.8 mg,
4-Phenylmorpholine (10c).6a Following the GP, morpholine 9c
(50 μL, 0.6 mmol, 1 equiv) and iodobenzene 7b (100 μL, 0.86 mmol,
1
71%). H NMR (500 MHz, CDCl3): 8.14 (d, 1H, J = 4.2 Hz), 7.44−
1
1.5 equiv) afforded 10c as a white solid (85.7 mg, 74%). H NMR
7.41 (m, 1H), 7.23 (d, 2H, J = 9.2 Hz), 6.89 (d, 2H, J = 9.2 Hz), 6.66
(t, 2H, J = 8.4 Hz), 6.48 (br s, 1H), 3.81 (s, 3H). 13C NMR (100
MHz, CDCl3): 157.5, 156.5, 148.5, 137.8, 133.4, 124.3, 114.8, 114.4,
107.4, 55.7. HRMS (ESI) calcd for C12H13N2O [M + H]+: 201.1028,
found 201.1003.
9-(Pyridin-2-yl)-9H-carbazole (13). Following the GP, carbazole 9e
(84 mg, 0.5 mmol, 1 equiv) and 2-bromopyridine 11 (71 μL, 0. 75
mmol, 1.5 equiv) afforded 12 as a white solid (90.6 mg, 78%). Mp:
159−161 °C. 1H NMR (400 MHz, CDCl3): 8.73 (d, 1H, J = 4.9 Hz),
8.12 (d, 2H, J = 7.3 Hz), 7.95−7.91 (m, 1H), 7.83 (d, 2H, J = 8.6 Hz),
7.63 (d, 1H, J = 7.9 Hz), 7.44 (t, 2H, J = 7.3 Hz), 7.33−7.29 (m, 3H).
13C NMR (100 MHz, CDCl3):152.0, 149.8, 139.7, 138.6, 126.4, 124.5,
(400 MHz, CDCl3): 7.26 (t, 2H, J = 8.1 Hz), 6.87 (dd, 3H, J = 8.1, 7.4
Hz), 3.83 (t, 4H, J = 5.2 Hz), 3.12 (t, 4H, J = 4.4 Hz); 13C NMR (100
MHz, CDCl3):151.4, 129.2, 120.1, 115.7, 66.9, 49.4. HRMS (ESI)
calcd for C10H14NO [M + H]+: 164.1075, found 164.1082.
1-(4-Methoxyphenyl)pyrrolidine (10d).6a Following the GP,
pyrrolidine 9d (57 μL, 0.7 mmol, 1 equiv) and p-iodoanisole 7a
(246 mg, 1.05 mmol, 1.5 equiv) afforded 10d as a white solid (89.3
1
mg, 72%). H NMR (500 MHz, CDCl3): 6.86 (d, 2H, J = 8.4 Hz),
6.55 (d, 2H, J = 9.2 Hz), 3.77 (s, 3H), 3.25 (t, 4H, J = 6.7 Hz), 2.03−
1.98 (m, 4H). 13C NMR (100 MHz, CDCl3):151.1, 143.2, 115.1,
112.9, 56.1, 48.5, 25.5. HRMS (ESI) calcd for C11H16NO [M + H]+:
178.1232, found 178.1240.
121.3, 121.1, 120.3, 119.2, 111.3, . HRMS (ESI) calcd for C17H13N2
1-(4-Methoxyphenyl)-1H-indole (10e).6g Following the GP, indole
9e (60 mg, 0.5 mmol, 1 equiv) and 4-iodoanisole 7a (175 mg, 0. 75
mmol, 1.5 equiv) afforded 10e as a white solid (73.5 mg, 77%). Mp:
[M + H]+: 245.1079, found 245.1082.
Synthesis of Carbazole Natural Products. Gram-Scale Syn-
thesis of 8a. In a large sealed tube, catalyst Pro-1 (541 mg, 1.62
I
J. Org. Chem. XXXX, XXX, XXX−XXX