The Journal of Organic Chemistry
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6.6 Hz, 0.5H), 4.29−4.19 (m, 1H), 4.01−3.92 (m, 1H), 3.77−3.69 (m,
0.5H), 3.66−3.59 (m, 1H), 3.43 (dd, J = 8.5, 6.6 Hz, 0.5H), 3.08 (dd, J
= 14.9, 7.4 Hz, 1H), 2.94 (t, J = 8.1 Hz, 0.5H), 2.80 (t, J = 8.1 Hz,
0.5H), 2.33 (s, 0.5H), 2.30 (s, 0.5H), 2.28 (s, 1H), 2.26 (s, 0.5H), 2.18
(s, 0.5H), 2.00 (d, J = 4.4 Hz, 1.5H), 1.95 (s, 0.8H), rotamers; 13C
NMR (75 MHz, CDCl3) δ 170.9, 170.7, 170.6, 170.6, 136.4, 136.3,
135.8, 135.6, 135.5, 135.4, 135.1, 131.6, 131.3, 131.0, 130.7, 130.4,
130.4, 130.3, 130.1, 129.9, 129.3, 129.1, 128.4, 127.9, 127.7, 127.6,
127.5, 127.1, 127.1, 126.5, 126.3, 126.2, 125.8, 125.8, 125.7, 122.4,
122.3, 122.2, 122.1, 122.0, 119.6, 119.6, 119.4, 119.3, 118.9, 118.8,
118.3, 118.2, 113.3, 113.1, 112.1, 112.0, 111.6, 111.5, 111.3, 111.2,
54.5, 51.8, 49.8, 49.1, 48.6, 47.9, 47.2, 46.9, 43.0, 29.1, 27.2, 24.9, 24.5,
23.9, 23.6, 21.9, 21.8, 21.5, 21.4, 20.1, 20.0, 19.9, rotamers; HRMS
(ESI) m/z calcd for C22H25N2O [M + H]+ 333.1967, found 333.1960.
N-Acetyl-N-3-(3,5-dimethoxyphenyl)prop-2-enyl-1-tryptamine
(SI6). Following general procedure VIII, the reaction of N-acetyl-N-3-
bromoprop-2-enyl-1-tryptamine (96 mg, 0.30 mmol), 3,5-dimethox-
yphenylboronic acid (70 mg, 0.39 mmol), Pd2(dba)3 (13.1 mg, 0.014
mmol), P(t-Bu)3 (1.0 M in THF, 40 μL), and KF (59.3 mg, 1.02
mmol) gave, after flash column chromatography (Et3N/MeOH/
CH2Cl2, 1:1:98), the title compound as an orange solid (101 mg,
90%): mp 116−117 °C; Rf = 0.48 (MeOH/CH2Cl2 (1:9), PMA, UV);
HPLC purity >95% (tR = 7.94, 7.95, 7.96 min); IR (neat) cm−1 3233,
2930, 1589, 1419, 1152, 735; 1H NMR (300 MHz, CDCl3) δ 8.61 (m,
0.9H), 7.65 (d, J = 7.8 Hz, 0.2H), 7.54 (dd, J = 16.6, 7.8 Hz, 0.5H),
7.41−7.31 (m, 1.2H), 7.24−6.86 (m, 3H), 6.63−6.32 (m, 3H), 6.28
(d, J = 2.2 Hz, 0.6H), 6.24−6.13 (m, 0.3H), 6.09−5.98 (m, 0.2H),
5.72−5.53 (m, 0.5H), 4.39 (dd, J = 6.5, 1.7 Hz, 0.5H), 4.17 (d, J = 6.2
Hz, 0.5H), 4.10 (dd, J = 6.3, 1.9 Hz, 0.5H), 3.00 (d, J = 3.9 Hz, 0.4H),
3.78 (s, 6H), 3.76− 3 0.68 (m, 0.7H), 3.60−3.56 (m, 1H), 3.52−3.42
(m, 0.6H), 3.11−2.84 (m, 2H), 2.16 (s, 0.7H), 2.03 (s, 0.8H), 1.99 (d,
J = 4.2 Hz, 1.5H), rotamers; 13C NMR (75 MHz, CDCl3) δ 170.9,
170.8, 170.6, 161.0, 161.0, 160.8, 160.7, 138.7, 138.6, 138.2, 138.0,
136.4, 136.3, 132.8, 132.1, 131.8, 131.6, 129.3, 128.5, 127.5, 127.1,
127.1, 125.7, 124.9, 122.5, 122.4, 122.2, 122.2, 122.1, 122.0, 121.9,
119.6, 119.5, 119.4, 119.3, 118.9, 118.8, 118.3, 118.3, 113.2, 113.1,
112.0, 112.0, 111.6, 111.5, 111.4, 111.2, 107.0, 107.0, 104.5, 104.5,
100.3, 100.2, 99.5, 55.5, 54.5, 51.4, 49.3, 48.7, 47.6, 47.6, 47.2, 43.5,
29.1, 24.8, 24.6, 23.8, 23.6, 22.0, 21.9, 21.5, 21.4, rotamers; HRMS
(ESI) m/z calcd for C23H27N2O3 [M + H]+ 379.2022, found 379.2021.
N-Acetyl-N-3-(4-nitrophenyl)prop-2-enyl-1-tryptamine (SI7). Fol-
lowing general procedure VIII, the reaction of N-acetyl-N-3-
bromoprop-2-enyl-1-tryptamine (87 mg, 0.27 mmol), 4-nitrophenyl-
boronic acid (59.7 mg, 0.36 mmol), Pd2(dba)3 (19.6 mg, 0.021 mmol),
P(t-Bu)3 (1.0 M in THF, 40 μL), and KF (64.1 mg, 1.10 mmol) gave,
after flash column chromatography (Et3N/MeOH/CH2Cl2, 1:1:98),
the title compound as an orange solid (76.1 mg, 77%): mp 116−117
°C; Rf = 0.50 (MeOH/CH2Cl2 (1:9), PMA, UV); HPLC purity >95%
(tR = 7.85, 7.92 min); IR (neat) cm−1 3246, 2925, 1622, 1512, 1338,
the title compound as an orange solid (77 mg, 78%): mp 124−125 °C;
Rf = 0.48 (MeOH/CH2Cl2 (1:9); PMA, UV); HPLC purity >95% (tR
= 7.80, 7.91 min); IR (neat) cm−1 3283, 2919, 1615, 1627, 1347, 749;
1H NMR (300 MHz, CDCl3) δ 8.35 (t, J = 29.5 Hz, 0.9H), 8.17−7.99
(m, 1.6H), 7.88−7.84 (m, 0.2H), 7.65−7.53 (m, 0.8H), 7.51−7.28 (m,
3H), 7.24−6.88 (m, 3H), 6.58 (dd, J = 11.7, 4.8 Hz, 0.5H), 6.47−6.22
(m, 0.7H), 6.09 (dt, J = 16.0, 5.2 Hz, 0.2H), 5.89−5.65 (m, 0.6H),
4.26 (dd, J = 6.4, 1.9 Hz, 0.7H), 4.17 (d, J = 5.7 Hz, 0.5H), 3.95 (ddd,
J = 6.7, 5.7, 1.8 Hz, 0.8H), 3.73 (t, J = 7.2 Hz, 0.4H), 3.63 (td, J = 7.2,
3.3 Hz, 1H), 3.52 (t, J = 7.2 Hz, 0.8H), 3.07 (dd, J = 14.6, 7.2 Hz, 1H),
2.97 (t, J = 7.3 Hz, 0.5H), 2.90 (t, J = 7.2 Hz, 0.7H), 2.15 (s, 0.6H),
2.03 (dd, J8.0, 4.7 = Hz, 2H), rotamers; 13C NMR (75 MHz, CDCl3)
δ 170.9, 170.8, 170.5, 148.6, 148.2, 138.5, 138.1, 138.0, 137.4, 136.5,
136.4, 134.8, 134.6, 132.4, 132.2, 131.9, 131.1, 130.1, 129.7, 129.6,
129.5, 129.3, 129.3, 129.2, 128.6, 128.0, 127.5, 127.3, 127.1, 126.9,
123.4, 123.2, 122.5, 122.4, 122.4, 122.3, 122.2, 122.1, 121.1, 120.9,
119.7, 119.6, 119.5, 119.4, 118.8, 118.5, 118.3, 118.0, 113.2, 113.0,
112.0, 111.8, 111.7, 111.5, 111.4, 111.3, 54.5, 51.4, 49.3, 49.0, 47.7,
47.5, 47.2, 43.8, 27.2, 27.1, 25.0, 25.0, 23.9, 23.8, 22.0, 21.9, 21.4, 21.4,
rotamers; HRMS (ESI) m/z calcd for C21H22N3O3 [M + H]+
364.1661, found 364.1658.
N-Acetyl-N-3-(4-(trifluoromethyl)phenyl)prop-2-enyl-1-trypt-
amine (SI9). Following general procedure VIII, the reaction of N-
acetyl-N-3-bromoprop-2-enyl-1-tryptamine (107 mg, 0.33 mmol), 4-
(trifluoromethyl)phenylboronic acid (79 mg, 0.41 mmol), Pd2(dba)3
(18.2 mg, 0.019 mmol), P(t-Bu)3 (1.0 M in THF, 50 μL), and KF (74
mg, 1.27 mmol) gave, after flash column chromatography (Et3N/
MeOH/CH2Cl2, 1:1:98), the title compound as an orange oil (106
mg, 82%): Rf = 0.59 (MeOH/CH2Cl2 (1:9); PMA, UV); HPLC purity
>95% (tR = 8.66, 8.72 min); IR (neat) cm−1 3271, 2927, 1614, 1322,
1110, 1065, 738; 1H NMR (300 MHz, CDCl3) δ 8.15 (t, J = 24.2 Hz,
0.9H), 7.66−7.52 (m, 2H), 7.49 −6.91 (m, 7.4H), 6.87 (s, 0.3H),
6.66−6.56 (m, 0.6H), 6.47−6.33 (m, 0.4H), 6.32−6.22 (m, 0.6H),
6.15−6.05 (m, 0.2H), 5.81−5.63 (m, 0.6H), 4.30 (dd, J = 6.5, 1.8 Hz,
0.8H), 4.17 (d, J = 6.2 Hz, 0.5H), 4.01 (dd, J = 6.3, 1.9 Hz, 0.6H), 3.93
(d, J = 4.2 Hz, 0.4H), 3.72 (t, J = 7.3 Hz, 0.4H), 3.62 (td, J = 7.5, 2.8
Hz, 1H), 3.48 (t, J = 4.5 Hz, 0.8H), 3.06 (q, J = 14.6, 7.4 Hz, 1H), 2,97
(t, J = 7.5 Hz, 0.6H), 2.88 (t, J = 7.5 Hz, 0.8H), 2.14 (s, 0.7H), 2.02 (s,
0.9H), 2.01 (s, 0.7H), 1.99 (s, 1H), rotamers; 13C NMR (75 MHz,
CDCl3) δ 1 171.1, 171.0, 170.9, 170.6, 140.3, 139.7, 136.5, 136.5,
131.3, 131.2, 130.9, 130.4, 130.4, 129.2, 129.1, 128.1, 127.7, 127.6,
127.4, 127.2, 127.1, 126.7, 125.7, 125.7, 125.6, 125.6, 125.5, 125.5,
125.4, 122.5, 122.5, 122.5, 122.4 (d, JC−F = 17.5 Hz), 122.3 (d, JC−F
=
22.7 Hz), 122.2, 122.2, 119.8, 119.8, 119.6, 119.5, 118.9, 118.8, 118.4,
118.2, 113.4, 113.2, 112.2, 112.1, 111.7, 111.6, 111.5, 111.4, 88.0, 54.7,
51.5, 49.4, 49.0, 47.8, 47.7, 47.5, 47.3, 43.8, 27.3, 25.1, 24.9, 24.0, 23.8,
22.1, 21.5, 21.5, rotamers; HRMS (ESI) m/z calcd for C22H22N2OF3
[M + H]+ 387.1679, found 387.1699.
N-Acetyl-N-3-(4-fluorophenyl)prop-2-enyl-1-tryptamine (SI10).
Following general procedure VIII, the reaction of N-acetyl-N-3-
bromoprop-2-enyl-1-tryptamine (93 mg, 0.29 mmol), 4-fluorophenyl-
boronic acid (45 mg, 0.32 mmol), Pd2(dba)3 (13.3 mg, 0.015 mmol),
P(t-Bu)3 (1.0 M in THF, 40 μL), and KF (60 mg, 1.03 mmol) gave,
after flash column chromatography (Et3N/MeOH/CH2Cl2, 1:1:98),
the title compound as a brown oil (78 mg, 80%): Rf = 0.53 (MeOH/
CH2Cl2 (1:9); PMA, UV); HPLC purity 89% (tR = 8.09 min); IR
(neat) cm−1 3270, 2925, 1615, 1454, 1224, 738; 1H NMR (300 MHz,
CDCl3) δ 8.71−8.44 (m, 1H), 7.70−7.53 (m, 0.7H), 7.48 (d, J = 7.9
Hz, 0.2H), 7.41−7.32 (m, 1.2H), 7.32−6.92 (m, 6H), 6.87 (d, J = 2.2
Hz, 0.2H), 6.57 (dd, J = 11.3, 9.5 Hz, 0.3H), 6.44−6.28 (m, 0.6H),
6.21 (q, J = 13.5, 6.5 Hz, 0.2H), 6.11 (t, J = 6.4 Hz, 0.1H), 6.04 (dt, J =
7.2, 6.3 Hz, 0.2H), 5.93 (dt, J = 15.8, 5.4 Hz, 0.2H), 5.70−5.52 (m,
0.3H), 4.33 (dd, J = 6.4, 1.8 Hz, 0.3H), 4.25 (dd, J = 6.5, 1.3 Hz,
0.4H), 4.14 (t, J = 7.1 Hz, 0.5H), 4.04 (dd, J = 6.2, 1.9 Hz,0.3H), 3.98
(dd, J = 6.1, 1.8 Hz, 0.3H), 3.90 (dd, J = 5.4, 1.5 Hz, 0.4H), 3.76−3.52
(m, 1.8H), 3.51−3.43 (m, 0.4H), 3.12−2.93 (m, 2H), 2.87 (t, J = 8.1
Hz, 0.5H), 2.15 (s, 0.5H), 2.13 (s, 0.4H), 2.05 (s, 0.3H), 2.03−1.97
(m, 1.5H), 1.92 (s, 0.5H), rotamers; 13C NMR (75 MHz, CDCl3) δ
171.0, 170.9, 170.8, 170.7, 170.6, 136.4, 131.5, 131.1, 130.9, 130.6 (d,
JC−F = 1.6 Hz), 130.6, 130.5, 130.5, 130.4 (d, JC−F = 8.0 Hz), 128.8,
1
738; H NMR (300 MHz, CDCl3) δ 8.25 (d, J = 19.1 Hz, 0.8H),
8.19−8.10 (m, 1.9H), 7.62 (d, J = 7.9 Hz, 0.2H), 7.55 (d, J = 7.8 Hz,
0.3H), 7.47−7.27 (m, 3H), 7.25−7.09 (m, 2H), 7.09−6.98 (m, 1H),
6.96−6.88 (m, 0.4H), 6.60 (d, J = 11.7 Hz, 0.5H), 6.48−6.28 (m,
0.8H), 6.17 (dt, J = 16.0, 5.1 Hz, 0.3H), 5.86−5.67 (m, 0.5H), 4.30−
4.14 (m, 1H), 4.00−3.90 (m, 0.8H), 3.73 (t, J = 7.3 Hz, 0.5H), 3.62
(td, J = 7.1, 3.8 Hz, 1H), 3.55−3.47 (m, 0.7H), 3.07 (dd, J = 14.1, 6.8
Hz, 1H), 2.94 (dt, J = 21.2, 7.1 Hz, 1H), 2.14 (s, 0.6H), 2.03 (s, 1H),
2.01 (s, 0.9H), rotamers; 13C NMR (75 MHz, CDCl3) δ 170.9, 170.8,
143.2, 136.4, 132.8, 132.0, 130.4, 130.2, 130.1, 129.7, 129.5, 129.4,
127.0, 127.0, 124.1, 124.1, 123.8, 123.7, 122.5, 122.4, 122.3, 122.2,
119.8, 119.7, 119.6, 119.5, 118.8, 118.6, 118.3, 118.1, 111.7, 111.6,
111.4, 54.6, 51.4, 49.3, 49.1, 47.8, 47.5, 44.0, 27.2, 25.1, 23.9, 22.0,
22.0, 21.4, 21.4, rotamers; HRMS (ESI) m/z calcd for C21H22N3O3 [M
+ H]+ 364.1661, found 364.1657.
N-Acetyl-N-3-(3-nitrophenyl)prop-2-enyl-1-tryptamine (SI8). Fol-
lowing general procedure VIII, the reaction of N-acetyl-N-3-
bromoprop-2-enyl-1-tryptamine (82 mg, 0.26 mmol), 3-nitrophenyl-
boronic acid (55 mg, 0.33 mmol), Pd2(dba)3 (13.4 mg, 0.015 mmol),
P(t-Bu)3 (1.0 M in THF, 40 μL), and KF (62 mg, 1.07 mmol) gave,
after flash column chromatography (Et3N/MeOH/CH2Cl2, 1:1:98),
12563
dx.doi.org/10.1021/jo402192s | J. Org. Chem. 2013, 78, 12545−12565