4
C. Zhang et al. / Tetrahedron xxx (2014) 1e5
6.88 (d, J¼8.4 Hz, 2H), 6.65 (d, J¼8.3 Hz, 1H), 6.27 (d, J¼1.7 Hz,
1H), 6.07 (dd, J¼8.3, 1.8 Hz, 1H), 5.85 (s, 2H), 4.18 (s, 2H), 3.81
(s, 3H); 13C NMR (100 MHz, CDCl3):
158.96, 148.41, 144.12,
d
139.74, 131.49, 128.93, 128.93, 114.12, 114.12, 108.73,
104.50, 100.67, 96.11, 55.41, 48.84; MS (ESI): m/z 258 [MþH]þ;
HRMS (ESI): calcd for
258.1120.
C
15H16NO3 [MþH]þ 258.1125, found
4.2.8. N-(4-Methoxybenzyl)quinolin-4-amine (3h). Yellow solid;
mp 116.7e117.5 ꢀC; 1H NMR (400 MHz, CDCl3):
d
8.56 (d, J¼5.3
Hz, 1H), 8.00 (d, J¼8.7 Hz, 1H), 7.74 (d, J¼8.5 Hz, 1H), 7.64 (t,
J¼8.0 Hz, 1H), 7.43 (t, J¼7.6 Hz, 1H), 7.33 (d, J¼8.6 Hz, 2H), 6.92
(d, J¼8.5 Hz, 2H), 6.48 (d, J¼5.3 Hz, 1H), 5.24 (brs, 1H), 4.46 (s,
1H), 4.45 (s, 1H), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
159.41, 151.23, 149.53, 148.53, 130.13, 129.57, 129.16, 129.10,
124.84, 119.45, 118.83, 114.44, 99.44, 55.47, 47.21; MS (ESI): m/z
265 [MþH]þ; HRMS (ESI): calcd for C17H17N2O [MþH]þ
265.1335, found 265.1341.
Scheme 3. The probable mechanism of CuI/Met-catalyzed Ullmann-type CeN cou-
pling reaction.
4.2.9. N-(4-Methoxybenzyl)pyridin-3-amine (3i). White solid; mp
150.6e150.9 ꢀC; 1H NMR (400 MHz, CDCl3):
d8.07 (d, J¼2.7 Hz, 1H),
7.97 (d, J¼4.6 Hz, 1H), 7.28 (d, J¼8.5 Hz, 2H), 7.08 (dd, J¼8.1, 4.4 Hz,
1H), 6.90e6.87 (m,3H), 4.27 (s, 2H), 3.81 (s, 3H); MS (ESI): m/z 215
[MþH]þ.
was concentrated under reduced pressure and the crude product
was purified by column chromatography to afford the corre-
sponding product 3.
4.2.10. N-Benzylaniline (3j). Yellow oil; 1H NMR (400 MHz, CDCl3):
4.2.1. N-(4-Methoxybenzyl)aniline
(3a). White
solid;
mp
d7.42e7.32 (m, 4H), 7.30e7.27 (m, 1H), 7.22e7.14 (m, 2H), 6.72 (t,
44.5e45.3 ꢀC; 1H NMR (400 MHz, CDCl3):
d7.30 (d, J¼8.4 Hz, 2H),
J¼7.3 Hz, 1H), 6.65 (d, J¼8.2 Hz, 2H), 4.34 (s, 2H), 4.03 (brs, 1H); MS
7.19 (t, J¼7.9 Hz, 2H), 6.89 (d, J¼8.6 Hz, 2H), 6.72 (t, J¼7.3 Hz, 1H),
6.65 (d, J¼7.8 Hz, 2H), 4.26 (s, 2H), 3.96 (brs, 1H), 3.81 (s, 3H); MS
(ESI): m/z 214 [MþH]þ.
(ESI): m/z 184 [MþH]þ.
4.2.11. (S)-N-(1-Phenylethyl)aniline (3k). Yellow oil; 1H NMR
(400 MHz, CDCl3): d 7.40e7.29 (m, 4H), 7.25e7.20 (m,1H), 7.12e7.06
4.2.2. 4-Methoxy-N-(4-methoxybenzyl)aniline (3b). White solid;
(m, 2H), 6.68e6.61 (m,1H), 6.53e6.50 (m, 2H), 4.49 (q, J¼6.7 Hz,1H),
mp 97.9e98.7 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.29 (d, J¼8.6 Hz,
4.03 (brs, 1H), 1.52 (d, J¼6.7 Hz, 3H); MS (ESI): m/z 198 [MþH]þ.
2H), 6.88 (d, J¼8.6 Hz, 2H), 6.78 (d, J¼8.9 Hz, 2H), 6.61 (d, J¼8.9 Hz,
2H), 4.21 (s, 2H), 3.81 (s, 3H), 3.75 (s, 3H); MS (ESI): m/z 244
[MþH]þ.
4.2.12. Diphenylamine (3l). Yellow solid; mp 54.5e55.4 ꢀC; 1H NMR
(400 MHz, CDCl3):
d
7.28 (t, J¼7.6 Hz, 4H), 7.09 (d, J¼8.1 Hz, 4H), 6.94
(t, J¼7.3 Hz, 2H), 5.71 (brs, 1H); MS (ESI): m/z 170 [MþH]þ.
4.2.3. 3-Methoxy-N-(4-methoxybenzyl)aniline (3c). Yellow oil; 1H
NMR (400 MHz, CDCl3):
d
7.30 (d, J¼8.6 Hz, 2H), 7.09 (t, J¼8.1 Hz,
4.2.13. 4-Phenylmorpholine (3m). Yellow solid; mp 54.0e54.9 ꢀC;
1H), 6.89 (d, J¼8.6 Hz, 2H), 6.31e6.25 (m, 2H), 6.21 (t, J¼2.2 Hz, 1H),
4.25 (s, 2H), 3.98 (brs, 1H), 3.81 (s, 3H), 3.77 (s, 3H); MS (ESI): m/z
244 [MþH]þ.
1H NMR (400 MHz, CDCl3):
d7.32e7.26 (m, 2H), 6.95e6.85 (m,
3H), 3.90e3.82 (m, 4H), 3.21e3.10 (m, 4H); MS (ESI): m/z 164
[MþH]þ.
4.2.4. 2-Methoxy-N-(4-methoxybenzyl)aniline (3d). White solid;
mp 86.5e87.5 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.31 (d, J¼8.7 Hz,
4.3. Experimental procedure for the synthesis of 5
2H), 6.91e6.82 (m, 3H), 6.78 (dd, J¼7.8, 1.1 Hz, 1H), 6.69e6.65 (m,
1H), 6.62 (dd, J¼7.8, 1.3 Hz, 1H), 4.54 (brs, 1H), 4.28 (s, 2H), 3.84 (s,
A solution of the diamine 4 (2 mmol), iodobenzene 2a
(6 mmol), CuI (0.2 mmol, 10 mol %), metformin hydrochloride
(0.4 mmol, 20 mol %), Cs2CO3 (6 mmol, 3 equiv), EtOH (5 mL)
was heated to reflux under N2. The reaction mixture was
stirred for the appropriate time (Table 4), and the progress of
the reaction was followed by TLC. After completion of the
reaction, the mixture was cooled to room temperature, and
the solid was removed by filter. The filtrate was concentrated
under reduced pressure and the crude product was purified
by column chromatography to afford the corresponding
product 5.
3H), 3.81 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 158.90, 146.88,
138.30, 131.68, 128.94, 121.39, 116.67, 114.08, 110.15, 109.47, 55.51,
55.42, 47.64; MS (ESI): m/z 244 [MþH]þ; HRMS (ESI): calcd for
C
15H18NO2 [MþH]þ 244.1332, found 244.1328.
4.2.5. 4-Chloro-N-(4-methoxybenzyl)aniline (3e). White solid; mp
84.1e84.3 ꢀC; 1H NMR (400 MHz, CDCl3):
d
7.27 (d, J¼8.6 Hz, 2H),
7.11 (d, J¼8.8 Hz, 2H), 6.88 (d, J¼8.6 Hz, 2H), 6.55 (d, J¼8.8 Hz, 2H),
4.23 (s, 2H), 3.98 (brs, 1H), 3.81 (s, 3H); MS (ESI): m/z 248 [MþH]þ.
4.2.6. N-(4-Methoxybenzyl)-4-nitroaniline (3f). Yellow solid; mp
145.1e145.3 ꢀC; 1H NMR (400 MHz, CDCl3):
d
8.08 (d, J¼8.4 Hz, 2H),
4.3.1. N1,N3-Diphenylpropane-1,3-diamine (5a). Yellow oil; 1H NMR
(400 MHz, CDCl3): d7.21e7.15 (m, 4H), 6.74e6.68 (m, 2H),
7.26 (d, J¼7.6 Hz, 2H), 6.90 (d, J¼7.8 Hz, 2H), 6.56 (d, J¼8.1 Hz, 2H),
4.75 (brs, 1H), 4.36 (s, 1H), 4.35 (s, 1H), 3.81 (s, 3H); MS (ESI): m/z
259 [MþH]þ.
6.64e6.60 (m, 4H), 3.73 (brs, 2H), 3.27 (t, J¼6.7 Hz, 4H), 1.95 (p,
J¼6.7 Hz, 2H); MS (ESI): m/z 227 [MþH]þ.
4.2.7. N-(4-Methoxybenzyl)benzo[d][1,3]dioxol-5-amine (3g).
4.3.2. N1,N4-Diphenylbutane-1,4-diamine (5b). Yellow solid; mp
Yellow oil; 1H NMR (400 MHz, CDCl3):
d
7.28 (d, J¼8.3 Hz, 2H),
36.5e37.3 ꢀC; 1H NMR (400 MHz, CDCl3):
d7.22e7.14 (m, 4H),