The Journal of Organic Chemistry
Note
stir bar and bis(cyclopentadienyl) zirconium chloride hydride (103
mg, 0.400 mmol, 1.00 equiv).28 THF (1.5 mL) and alkene (0.400
mmol, 1.00 equiv) were added. The vial was sealed with a cap
equipped with a PTFE-lined septum and stirred at room temperature.
After 0.5−4 h, the reaction mixture became homogeneous, and
hydroxylamine-O-sulfonic acid (67.9 mg, 0.600 mmol, 1.5 equiv) was
added. The vial was resealed, stirred at room temperature for 30 min,
and removed from the drybox. The reaction was diluted with wet THF
(5 mL) and concentrated in vacuo. The crude solids were dissolved in
aqueous 1 M HCl (5 mL), transferred to a separatory funnel, and
washed twice with Et2O. The combined washes were extracted once
more with 5 mL of 1 M HCl, and the combined aqueous phases were
basified to pH >8 with 1 M NaOH and extracted twice with Et2O. The
organic phases from the second extraction were washed with brine,
dried with Na2SO4, and concentrated in vacuo to yield the desired
product.
General Procedure C for the Hydrozirconation/Amination of
Alkenes. General Procedure A was followed until the workup step.
The crude solids were dissolved in aqueous 1 M NaOH (5 mL),
transferred to a separatory funnel, diluted with H2O, and extracted
twice with Et2O. The combined organic phases were washed with
brine, dried with Na2SO4, and concentrated in vacuo. The crude
residue was purified via column chromatography, eluting with 0.5%
NH4OH, 1−10% MeOH in DCM (v/v).
equiv) was added. The vial was resealed, removed from the drybox,
and heated at 50 °C for 30 min with stirring. The reaction was cooled
to room temperature, diluted with wet THF (2 mL), and concentrated
in vacuo. The crude solids were dissolved in aqueous 1 M HCl (5
mL), transferred to a separatory funnel, diluted with H2O, and washed
twice with Et2O. The combined washes were extracted once more with
5 mL of 1 M HCl, and the combined aqueous phases were basified to
pH >8 with aqueous 1 M NaOH and extracted twice with Et2O. The
organic phases from the second extraction were washed with brine,
dried with Na2SO4, and concentrated in vacuo to yield 82 mg of the
desired product as a white solid (92%). NMR analysis was performed
at 60 °C to minimize peak broadening, due to constrained rotation at
C9: 1H NMR (600 MHz, CDCl3) δ 8.74 (d, J = 4.4 Hz 1H), 8.03 (d, J
= 9.2 Hz, 1H), 7.55 (s, 1H), 7.47 (d, J = 4.2 Hz, 1H), 7.41−7.28 (m,
6H), 5.82−5.64 (m, 1H), 4.55−4.43 (m, 2H), 4.01 (s, 3H), 3.70−3.56
(m, 1H), 3.35−3.21 (m, 2H), 2.90−2.78 (m, 1H), 2.60 (m, 3H), 2.39
(s, 3H), 2.08−1.97 (m, 1H), 1.91−1.75 (m, 3H), 1.65−1.47 (m, 4H),
1.27 (br s, 1H); 13C NMR (151 MHz, CDCl3) δ 158.4, 150.4,
147.3(×2), 144.7, 137.4, 131.8, 128.5, 127.9, 127.7, 127.2, 122.4,
118.6, 101.2, 77.2, 71.3, 59.9, 57.5, 56.5, 48.6, 43.3, 34.8, 32.8, 32.4,
29.7, 25.7; HRMS (m/z + 1) Calc’d 446.2802 Found 446.2799;
HRMS−ESI (m/z) [M + H]+ calcd for C28H36N3O2, 446.2802; found
446.2799.
2-(3-Methylaminopropyl)phenyl-2,3,4,6-tetra-O-benzyl-α-D-
mannopyranoside. General Procedure C. 26 mg (colorless solid,
N-(3-Phenylpropyl)octylamine. In a drybox, an oven-dried, 1
dram vial was charged with a stir bar, and bis(cyclopentadienyl)
zirconium chloride hydride (51.6 mg, 0.200 mmol, 1.00 equiv),28 THF
(0.75 mL), and 1-octene (31.4 L, 0.200 mmol, 1.00 equiv) were added.
The vial was sealed with a cap equipped with a PTFE-lined septum
and stirred at room temperature. After 1 h the reaction mixture
became homogeneous, and N-(3-phenylpropyl)hydroxylamine-O-
sulfonic acid (69.6 mg, 0.300 mmol, 1.5 equiv) was added. The vial
was resealed, removed from the drybox, and heated at 80 °C for 30
min with stirring. The reaction was cooled to room temperature,
diluted with wet THF (2 mL), and concentrated in vacuo. The crude
solids were dissolved in aqueous 1 M NaOH (5 mL), transferred to a
separatory funnel, diluted with H2O, and extracted twice with Et2O.
The combined organic phases were washed with brine, dried with
Na2SO4, and concentrated in vacuo. The crude residue was purified via
column chromatography eluting with 0.5% NH4OH, 1−10% MeOH
in DCM (v/v) to yield 37 mg of N-(3-phenylpropyl)octylamine (clear
1
66%): H NMR (500 MHz, CDCl3) δ 7.45−7.26 (m, 18H), 7.24−
7.08 (m, 5H), 6.94 (td, J = 7.3 Hz, 1.2 Hz, 1H), 5.58 (d, J = 1.8 Hz,
1H), 4.93 (d, J = 10.8 Hz, 1H), 4.80 (s, 1H), 4.80 (s, 1H), 4.71 (m,
2H), 4.67 (d, J = 12.0 Hz, 1H), 4.56 (d, J = 10.8 Hz, 1H), 4.48 (d, J =
11.9 Hz, 1H), 4.17 (t, J = 9.4 Hz, 1H), 4.07 (dd, J = 9.4 Hz, 3.0 Hz,
1H), 3.98−3.92 (m, 1H), 3.88−3.76 (m, 2H), 3.70 (d, J = 9.5 Hz,
1H), 2.56−2.47 (m, 4H), 2.35 (s, 3H), 1.75−1.67 (m, 2H); 13C NMR
(151 MHz, CDCl3) δ 154.3, 138.5, 138.38, 138.34, 138.2, 131.0, 129.9,
128.4, 128.4, 128.3, 128.2, 127.9, 127.8, 127.8, 127.74, 127.71, 127.68,
127.6, 127.4, 127.2, 122.1, 114.5, 96.5, 79.9, 75.1, 74.9, 74.8, 73.3,
72.73, 72.67, 72.4, 69.1, 51.8, 36.5, 30.3, 28.0; HRMS−ESI (m/z) [M
+ H]+ calcd for C44H50N1O6, 688.3633; found 688.3616.
(3,3-Dimethyl)butylmethylamine. General procedure A was
followed, using 1.10 equiv of 3,3-dimethyl-1-butene (56.7 μL, 0.400
mmol) to yield 42 mg (clear oil, 91%): 1H NMR (400 MHz, CDCl3) δ
2.63−2.52 (m, 2H), 2.44 (s, 3H), 2.21 (s, 2H), 1.45−1.32 (br s, 1H),
0.89 (s, 9H); 13C NMR (101 MHz, CDCl3) δ 48.2, 43.7, 36.4, 29.8,
29.5.
1
oil, 74%): H NMR (600 MHz, CDCl3) δ 7.34−7.27 (m, 2H), 7.25−
7.14 (m, 3H), 2.74−2.61 (m, 4H), 2.59 (t, J = 7.3 Hz, 2H), 1.89−1.75
(m, 2H), 1.47 (m, 2H), 1.36−1.18 (m, 10H), 0.88 (t, J = 6.9 Hz, 3H);
13C NMR (151 MHz, CDCl3) δ 142.2, 128.3, 128.3, 125.7, 50.0, 49.5,
(6-Chloro)hexylmethylamine. General procedure A. 50 mg
1
(clear oil, 83%): H NMR (600 MHz, CDCl3) δ 3.53 (t, J = 6.7
Hz, 2H), 2.59 (t, J = 7.2 Hz, 2H), 2.44 (s, 3H), 2.07 (br s, 1H), 1.81−
1.71 (m, 2H), 1.58−1.47 (m, 2H), 1.47−1.40 (m, 2H), 1.40−1.28 (m,
2H); 13C NMR (101 MHz, CDCl3) δ 51.8, 45.0, 36.3 32.4, 29.5, 26.7,
26.5; HRMS−ESI (m/z) [M + H]+ calcd for C7H17ClN, 150.1045;
found 150.1044.
N-Methyl octylamine. General procedure A. 51 mg (clear oil,
89%): 1H NMR (400 MHz, CDCl3) δ 2.54 (t, J = 7.2 Hz, 2H), 2.41 (s,
3H), 1.62−1.53 (br s, 1H), 1.52−1.41 (m, 2H), 1.26 (m, 10H), 0.86
(t, J = 6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 52.1, 36.4, 31.8,
29.8, 29.5, 29.2, 27.3, 22.6, 14.0.30
33.7, 31.8, 31.7, 30.1, 29.5, 29.2, 27.4, 22.6, 14.1.
N-(tert-Butoxy-carbonyl)-(2,2-diphenyl-heptyl)-7-methyla-
mino)-methylamine. General procedure C. 120 mg (mixture of
1
rotamers, clear oil, 74%): H NMR (600 MHz, CDCl3) δ 7.34−7.20
(m, 5H), 7.18−7.13 (m, 5H), 4.09−3.88 (m, 2H), 2.54−2.42 (m, 2H),
2.38 (s, 3H), 2.18−1.87 (m, 6H), 1.41 (m, 9H), 1.34−1.17 (m, 2H),
1.11−0.94 (m, 2H); 13C NMR (151 MHz, CDCl3) δ 186.5, (186.1),
147.5, (146.5), 128.5, (128.3), 127.8, 126.0, (125.8), 79.8, (79.1), 57.9,
(56.6), 52.1, (51.8), 51.3, (51.0), 36.5, 36.4, (36.3), 29.8, (29.3), 28.4,
28.1, (27.8), 24.4, (24.1); HRMS−ESI (m/z) [M + H]+ calcd for
C26H39N2O2, 411.3007; found 411.2999.
N-Methyl(3-trimethylsilyl)propylamine. General procedure A.
1
48 mg (yellow oil, 83%): H NMR (500 MHz, CDCl3) δ 2.54 (t, J =
9-O-Benzyl-10,11-dihydro-11-methylamino-quinine. In a
drybox, an oven-dried, screw-top, 1 dram vial was charged with a
stir bar, and bis(cyclopentadienyl) zirconium chloride hydride (51.6
mg, 0.200 mmol, 1.00 equiv). THF-d8 (1.0 mL) and 9-O-benzyl
quinine (82.9 mg, 0.200 mmol, 1.00 equiv) were added, the vial was
sealed with a cap equipped with a PTFE-lined septum, and the
reaction was stirred at room temperature. After 30 min the reaction
mixture became homogeneous, and the solution was analyzed by
NMR spectroscopy. The amount of remaining olefin was determined
to be approximately 0.2 equiv, and a further portion of bis-
(cyclopentadienyl) zirconium chloride hydride (16.6 mg, 0.0640
mmol, 0.322 equiv) was added. The reaction was stirred for 1 h, at
which point the reaction mixture became homogeneous, and N-
methylhydroxylamine-O-sulfonic acid (38.1 mg, 0.300 mmol, 1.50
7.1 Hz, 2H), 2.41 (s, 3H), 2.13 (br s, 1H), 1.52−1.37 (m, 2H), 0.49−
0.42 (m, 2H), −0.04 (s, 9H).13C NMR (75 MHz, CDCl3) δ 55.5, 36.5,
24.3, 14.3, −1.5.
N-Methyl(3-phenyl)propylamine. General procedure A. 50 mg
(yellow oil, 83%): 1H NMR (400 MHz, CDCl3) δ 7.37−7.29 (m, 2H),
7.28−7.20 (m, 3H), 2.78−2.60 (m, 4H), 2.49 (s, 3H), 1.88 (m, 2H);
13C NMR (101 MHz, CDCl3) δ 142.1, 128.3, 128.3, 125.7, 51.5, 36.3,
33.6, 31.4.31
N-(2-Cyclohexyl)ethyl methylamine. General procedure A. 50
1
mg (yellow oil, 89%): H NMR (400 MHz, CDCl3) δ 2.62−2.49 (m,
2H), 2.40 (s, 3H), 1.78−1.52 (m, 4H), 1.35 (m, 2H), 1.28−1.00 (m,
5H), 0.88 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 49.7, 37.5, 36.5,
35.6, 33.4, 26.6, 26.3.32
8913
dx.doi.org/10.1021/jo401498w | J. Org. Chem. 2013, 78, 8909−8914