The Journal of Organic Chemistry
Article
2-(o-Tolyl)ethan-1,1,2,2-d4-1-amine Hydrochloride20 (2h,
Scheme 3). According to the general procedure, the reaction of 2-
(o-tolyl)acetonitrile (26.2 mg, 0.200 mmol), samarium(II) iodide
(0.100 M in THF; 18.0 mL, 1.80 mmol), triethylamine (0.66 mL, 4.8
mmol), and D2O (0.43 mL, 24 mmol) afforded 31.3 mg of 2h in 89%
of 2-(4-fluorophenyl)acetonitrile (27.0 mg, 0.200 mmol), samarium-
(II) iodide (0.100 M in THF; 18.0 mL, 1.80 mmol), triethylamine
(0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24 mmol) afforded 27.3 mg
of 2o in 76% yield as a white solid: 1H NMR (300 MHz, DMSO-d6):
δ 8.13 (br, 3H), 7.30 (m, 2H), 7.15 (m, 2H); 13C{1H} NMR (75
MHz, DMSO-d6): δ 161.6 (d, JC−F = 242.2 Hz), 133.5 (d, JC−F = 3.1
Hz), 130.6 (d, JC−F = 8.0 Hz), 115.3 (d, JC−F = 21.2 Hz), 40.6 (m),
31.2 (m); HRMS (ESI-TOF) m/z: M+ calcd for C8H7D4FN,
144.1121; found, 144.1121.
1
yield as a white solid: H NMR (300 MHz, DMSO-d6): δ 8.26 (br,
3H), 7.19−7.11 (m, 4H), 2.28 (s, 3H); 13C{1H} NMR (75 MHz,
DMSO-d6): δ 136.0, 135.5, 130.2, 129.0, 126.7, 126.1, 38.2 (m), 29.5
(m), 18.8.
2-(3-Fluorophenyl)ethan-1,1,2,2-d4-1-amine Hydrochloride18
(2p, Scheme 3). According to the general procedure, the reaction
of 2-(3-fluorophenyl)acetonitrile (27.0 mg, 0.200 mmol), samarium-
(II) iodide (0.100 M in THF; 18.0 mL, 1.80 mmol), triethylamine
(0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24 mmol) afforded 35.2 mg
of 2p in 98% yield as a white solid: 1H NMR (300 MHz, DMSO-d6):
δ 8.17 (br, 3H), 7.37 (m, 1H), 7.18−7.03 (m, 3H); 13C{1H} NMR
2-(3,5-Dimethylphenyl)ethan-1,1,2,2-d4-1-amine Hydrochlor-
ide21 (2i, Scheme 3). According to the general procedure, the
reaction of 2-(3,5-dimethylphenyl)acetonitrile (29.0 mg, 0.200
mmol), samarium(II) iodide (0.100 M in THF; 18.0 mL, 1.80
mmol), triethylamine (0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24
mmol) afforded 34.5 mg of 2i in 91% yield as a white solid: 1H NMR
(300 MHz, DMSO-d6): δ 7.99 (br, 3H), 6.87 (m, 1H), 6.85 (m, 2H),
2.24 (s, 6H); HRMS (ESI-TOF) m/z: M+ calcd for C10H12D4N,
154.1528; found, 154.1528.
(75 MHz, DMSO-d6): δ 162.2 (d, JC−F = 243.4 Hz), 140.2 (d, JC−F
=
7.7 Hz), 130.4 (d, JC−F = 8.4 Hz), 124.8 (d, JC−F = 2.8 Hz), 115.4 (d,
JC−F = 21.3 Hz), 113.5 (d, JC−F = 20.9 Hz), 40.0 (m), 31.4 (m);
HRMS (ESI-TOF) m/z: M+ calcd for C8H7D4FN, 144.1121; found,
144.1121.
2-(4-Isopropylphenyl)ethan-1,1,2,2-d4-1-amine Hydrochloride22
(2j, Scheme 3). According to the general procedure, the reaction of 2-
(4-isopropylphenyl)acetonitrile (31.8 mg, 0.200 mmol), samarium(II)
iodide (0.100 M in THF; 18.0 mL, 1.80 mmol), triethylamine (0.66
mL, 4.8 mmol), and D2O (0.43 mL, 24 mmol) afforded 35.9 mg of 2j
in 88% yield as a white solid: 1H NMR (300 MHz, DMSO-d6): δ 8.22
(br, 3H), 7.20−7.14 (m, 4H), 2.84 (m, 1H), 1.17 (d, J = 6.9 Hz, 6H);
13C{1H} NMR (75 MHz, DMSO-d6): δ 146.7, 134.6, 128.5, 126.4,
2-(2,4-Difluorophenyl)ethan-1,1,2,2-d4-1-amine Hydrochloride26
(2q, Scheme 3). According to the general procedure, the reaction of
2-(2,4-difluorophenyl)acetonitrile (30.6 mg, 0.200 mmol), samarium-
(II) iodide (0.100 M in THF; 18.0 mL, 1.80 mmol), triethylamine
(0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24 mmol) afforded 34.4 mg
of 2q in 87% yield as a white solid: 1H NMR (300 MHz, DMSO-d6):
δ 8.18 (br, 3H), 7.41 (m, 1H), 7.23 (m, 1H), 7.07 (m, 1H); 13C{1H}
NMR (75 MHz, methanol-d4): δ 163.8 (dd, JC−F = 247.0, 12.1 Hz),
162.6 (dd, JC−F = 247.1, 12.1 Hz), 133.3 (dd, JC−F = 9.7, 6.1 Hz),
120.8 (dd, JC−F = 16.1, 3.8 Hz), 112.7 (dd, JC−F = 21.3, 3.8 Hz), 104.8
(dd, JC−F = 26.1, 26.1 Hz), 40.1 (m), 26.9 (m).
40.0 (m), 33.0, 31.6 (m), 23.8; HRMS (ESI-TOF) m/z: M+ calcd for
C11H10D4N, 168.1685; found, 168.1684.
2-(4-(tert-Butyl)phenyl)ethan-1,1,2,2-d4-1-amine Hydrochlor-
ide23 (2k, Scheme 3). According to the general procedure, the
reaction of 2-(4-(tert-butyl)phenyl)acetonitrile (34.7 mg, 0.200
mmol), samarium(II) iodide (0.100 M in THF; 18.0 mL, 1.80
mmol), triethylamine (0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24
mmol) afforded 42.7 mg of 2k in 98% yield as a white solid: 1H NMR
(300 MHz, DMSO-d6): δ 8.21 (br, 3H), 7.33 (m, 2H), 7.17 (m, 2H),
1.25 (s, 9H); 13C{1H} NMR (75 MHz, DMSO-d6): δ 148.9, 134.3,
128.2, 125.2, 40.0 (m), 34.1, 31.5 (m), 31.1; HRMS (ESI-TOF) m/z:
M+ calcd for C12H16D4N, 182.1841; found, 182.1840.
2-(4-Chloro-3-fluorophenyl)ethan-1,1,2,2-d4-1-amine Hydro-
chloride27 (2r, Scheme 3). According to the general procedure, the
reaction of 2-(4-chloro-3-fluorophenyl)acetonitrile (33.9 mg, 0.200
mmol), samarium(II) iodide (0.100 M in THF; 18.0 mL, 1.80 mmol),
triethylamine (0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24 mmol)
1
afforded 36.4 mg of 2r in 85% yield as a white solid: H NMR (300
2-(3-Methoxyphenyl)ethan-1,1,2,2-d4-1-amine Hydrochloride18
(2l, Scheme 3). According to the general procedure, the reaction of
2-(3-methoxyphenyl)acetonitrile (29.4 mg, 0.200 mmol), samarium-
(II) iodide (0.100 M in THF; 18.0 mL, 1.80 mmol), triethylamine
(0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24 mmol) afforded 34.5 mg
of 2l in 90% yield as a white solid: 1H NMR (300 MHz, DMSO-d6): δ
8.19 (br, 3H), 7.22 (m, 1H), 6.86−6.77 (m, 3H), 3.73 (s, 3H);
13C{1H} NMR (75 MHz, DMSO-d6): δ 159.4, 138.9, 129.6, 120.7,
MHz, DMSO-d6): δ 8.19 (br, 3H), 7.53 (m, 1H), 7.38 (m, 1H), 7.15
(m, 1H); 13C{1H} NMR (75 MHz, DMSO-d6): δ 157.1 (d, JC−F
=
246.1 Hz), 139.2 (d, JC−F = 7.2 Hz), 130.5, 126.2 (d, JC−F = 3.4 Hz),
117.6 (d, JC−F = 17.4 Hz), 117.2 (d, JC−F = 20.8 Hz), 38.3 (m), 31.2
(m).
2-Phenylpropan-1,1,2-d3-1-amine Hydrochloride17 (2s, Scheme
3). According to the general procedure, the reaction of 2-
phenylpropanenitrile (26.2 mg, 0.200 mmol), samarium(II) iodide
(0.100 M in THF; 18.0 mL, 1.80 mmol), triethylamine (0.66 mL, 4.8
mmol), and D2O (0.43 mL, 24 mmol) afforded 29.3 mg of 2s in 84%
114.2, 112.2, 55.0, 40.5 (m), 32.0 (m); HRMS (ESI-TOF) m/z: M+
calcd for C9H10D4NO, 156.1321; found, 156.1320.
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yield as a white solid: H NMR (300 MHz, DMSO-d6): δ 8.05 (br,
2-(3,5-Dimethoxyphenyl)ethan-1,1,2,2-d4-1-amine Hydrochlor-
ide24 (2m, Scheme 3). According to the general procedure, the
reaction of 2-(3,5-dimethoxyphenyl)acetonitrile (35.4 mg, 0.200
mmol), samarium(II) iodide (0.100 M in THF; 18.0 mL, 1.80
mmol), triethylamine (0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24
3H), 7.37−7.25 (m, 5H), 1.24 (s, 3H); 13C{1H} NMR (75 MHz,
DMSO-d6): δ 142.8, 128.6, 127.1, 126.8, 44.3 (m), 36.7 (m), 19.1.
2-(Benzo[b]thiophen-3-yl)ethan-1,1,2,2-d4-1-amine Hydrochlor-
ide17 (2t, Scheme 3). According to the general procedure, the
reaction of 2-(benzo[b]thiophen-3-yl)acetonitrile (34.6 mg, 0.200
mmol), samarium(II) iodide (0.100 M in THF; 18.0 mL, 1.80 mmol),
triethylamine (0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24. mmol)
1
mmol) afforded 43.5 mg of 2m in 98% yield as a white solid: H
NMR (300 MHz, DMSO-d6): δ 6.41 (d, J = 2.2 Hz, 2H), 6.35 (t, J =
2.2 Hz, 1H), 3.72 (s, 6H); 13C{1H} NMR (75 MHz, DMSO-d6): δ
160.5, 140.0, 106.6, 98.4, 55.1, 39.8 (m), 33.2 (m); HRMS (ESI-
TOF) m/z: M+ calcd for C10H12D4NO2, 186.1427; found, 186.1425.
2-(4-(Methylthio)phenyl)ethan-1,1,2,2-d4-1-amine Hydrochlor-
ide25 (2n, Scheme 3). According to the general procedure, the
reaction of 2-(4-(methylthio)phenyl)acetonitrile (32.6 mg, 0.200
mmol), samarium(II) iodide (0.100 M in THF; 18.0 mL, 1.80 mmol),
triethylamine (0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24 mmol)
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afforded 41.8 mg of 2t in 96% yield as a white solid: H NMR (300
MHz, DMSO-d6): δ 7.99 (m, 1H), 7.91 (m, 1H), 7.59 (s, 1H), 7.48−
7.33 (m, 2H); 13C{1H} NMR (75 MHz, DMSO-d6): δ 139.7, 138.3,
131.6, 124.4, 124.2, 123.8, 122.9, 121.6, 40.3 (m), 25.2 (m).
2-(5-Methoxy-1H-indol-3-yl)ethan-1,1,2,2-d4-1-amine Hydro-
chloride28 (2u, Scheme 3). According to the general procedure, the
reaction of 2-(5-methoxy-1H-indol-3-yl)acetonitrile (37.2 mg, 0.200
mmol), samarium(II) iodide (0.100 M in THF; 18.0 mL, 1.80 mmol),
triethylamine (0.66 mL, 4.8 mmol), and D2O (0.43 mL, 24 mmol)
1
afforded 40.7 mg of 2n in 98% yield as a white solid: H NMR (300
MHz, DMSO-d6): δ 8.24 (br, 3H), 7.24−7.17 (m, 4H), 2.44 (s, 3H);
1
13C{1H} NMR (75 MHz, DMSO-d6): δ 136.2, 134.0, 129.2, 126.4,
afforded 36.0 mg of 2u in 78% yield as a white solid: H NMR (300
39.8 (m), 31.4 (m), 14.9; HRMS (ESI-TOF) m/z: M+ calcd for
C9H10D4NS, 172.1093; found, 172.1091.
MHz, DMSO-d6): δ 10.86 (br, 1H), 7.25 (d, J = 8.7 Hz, 1H), 7.18 (d,
J = 1.7 Hz, 1H), 7.09 (d, J = 2.3 Hz, 1H), 6.73 (dd, J = 8.7, 2.3 Hz,
1H), 3.76 (s, 3H); 13C{1H} NMR (75 MHz, DMSO-d6): δ 153.1,
131.4, 127.2, 123.8, 112.1, 111.2, 109.5, 100.1, 55.4, 40.7 (m), 23.5
2-(4-Fluorophenyl)ethan-1,1,2,2-d4-1-amine Hydrochloride17
(2o, Scheme 3). According to the general procedure, the reaction
F
J. Org. Chem. XXXX, XXX, XXX−XXX