Scott E. Denmark et al.
FULL PAPERS
4.0 mmol) at À418C. The resulting mixture was stirred for
30 min, and a toluene solution (10 mL) of imine 9 (526 mg,
2.01 mmol) was added over a period of 5 min. The remain-
ing imine was washed in 5 mL of toluene, twice. This yellow
solution was stirred for 1 h at À418C and quenched with
MeOH (2 mL) at that temperature. The reaction mixture
was warmed to room temperature, and diluted with TBME
(20 mL) and water (20 mL). The mixture was extracted with
TBME (350 mL). The combined organic layers were
washed with brine (200 mL) and then dried over Na2SO4.
Concentration followed by SiO2 column chromatography
(hexane/EtOAc, 10:1) afforded recovered 12cc (746 mg,
98%). The desired amine 18 (yield: 531 mg, 95%) was ob-
tained by continued elution (hexane/EtOAc, 3:1). An ana-
lytical sample of 18 was obtained after Kugelrohr distilla-
tion: bp 190–1958C (0.4 mmHg); [a]2D3: À158.4 (c 0.87,
HC(6’)], 6.57 [d, J=16.0, 1H, HC(4)], 6.22 [dd, J=6.0 Hz,
16.0, 1H, HC(3)], 4.07 [dq, J=6.0, 6.6 Hz, 1H, HC(4)], 3.74
(s, 3H, OMe), 1.39 (d, J=6.6, 3H, Me); 13C NMR: d=152.0
[C(4’)], 141.49 [C(1’)], 136.94 [C(5)], 133.47 [C(4)], 129.14
[C(3)], 128.41 [C(7), C(9)], 127.21 [C(8)], 126.21 [C(6),
C(10)], 114.48 [C(3’), C(5’)], 114.26 [C(2’), C(6’)], 55.63
(OMe), 51.73 [C(2)], 22.00 [C(1)]; IR (KBr): n=3397(s),
3079 (m), 3057 (s), 3025 (s), 2966 (s), 2831 (s), 1627 (m),
1577 (s), 1494 (s), 1463 (s), 1447 (s), 1406 (m), 1370 (s), 1310
(s),1291 (s), 1233 (s), 1177 (s), 1159 (s), 1038 (s), 967 (s),
818 cmÀ1 (s); MS (70 eV): m/z=254 (M+ +1, 7.5), 253 (M+,
41), 238 (M+À15, 8), 206 (0.6), 160 (1), 146 (5), 131 (100),
108 (19), 91 (30), 77 (11), 62 (7); chiral HPLC: tR (S)-17,
27.07 (7.5%); tR (R)-17, 31.68 (92.5%) (Diacel AD column;
hexane/EtOH, 99.2/0.8, 0.5 mLminÀ1); anal. calcd. for
C17H19NO (227.31): C 80.60, H 7.56, N 5.53; found: C 80.56,
H 7.58, N, 5.50.
1
CHCl3); H NMR: d=8.17 (d, J=8.3 Hz, 1H, C10H7), 7.91
(d, J=8.9 Hz, 1H, C10H7), 7.75 (d, J=8.1 Hz, 1H, C10H7),
7.67 (d, J=7.0 Hz, 1H, C10H7), 7.49–7.60 [m, 2H, HC(8),
HC(9)], 7.42 [t, J=7.7 Hz, HC(5)], 6.64–6.69 [m, 2H,
(R)-N-(4-Methoxyphenyl)-a-
HC(3’), HC(5’)], 6.43–6.69 [m, 2H, HC(2’), HC(6’)], 5.23 [q, butylbenzenepropan
ACHTREaUGN mine (19). Stoichiometric with 4
J=6.6 Hz, 1H, HC(2)], 3.68 (s, 3H, OMe), 1.65 (d, J=
6.6 Hz, 3H, Me); 13C NMR: d=151.69, 141.27, 140.12,
133.98, 130.65, 129.02, 127.22, 125.91, 125.79, 125.29, 122.51,
122.20, 114.66, 114.18, 55.52, 49.91, 23.60; IR (KBr); n=
3400 (s), 3051 (s), 2900 (s), 2831 (s), 1766 (s), 1761 (s), 1754
(s), 1746 (s), 1743 (s), 1738 (s), 1733 (s), 1729 (s), 1717 (s),
1510 (s), 1463 (s), 1440 (s), 1291 (s), 1248 (s), 1204 (s), 1174
(s), 1038 (s), 818 (s), 800 cmÀ1 (s); MS (70 eV): m/z=278
(M+ +1, 5), 363 (M+, 26), 262 (M+À15, 9), 155
(C10H7CHMe+, 100), 123 (35), 108 (10, 84 (9), 77 (6); chiral
HPLC: tR (R)-18, 23.58 (92%); tR (S)-18, 24.72 (8%) (Diacel
OD column; hexane/EtOH, 99.5/0.5, 0.5 mLminÀ1); anal.
calcd. for C19H19NO (277.37): C 82.28, H 6.90, N 5.05;
found: C 82.31, H 6.89, N 5.04.
(Table 13, entry 9)
To a solution of 4 (470 mg, 2.01 mmol) in Et2O (20 mL) in a
flame-dried, 250-mL, 3-necked, round-bottom flask
equipped with a stir bar, a thermometer, a septum and a ni-
trogen inlet was added n-BuLi (1.65 mL, 2.43M in Et2O,
4.01 mmol) at À948C. The resulting mixture was stirred for
30 min, and a Et2O solution (14 mL) of imine 11 (481 mg,
2.01 mmol) was added over a period of 5 min. The remain-
ing imine was washed in 3 mL of Et2O, twice. The resulting
yellow solution was stirred for 1 h at À948C and quenched
with MeOH (0.9 mL) at that temperature. The reaction mix-
ture was warmed to room temperature, and diluted with
TBME (20 mL) and water (15 mL). The mixture was ex-
tracted with TBME (350 mL). The combined organic
layers were washed with brine (200 mL) and then dried over
Na2SO4. Concentration followed by SiO2 column chromatog-
raphy (hexane/EtOAc, 15:1) afforded the amine 19 (yield:
539 mg, 90%) as a pale-yellow oil. An analytical sample of
19 was obtained after Kugelrohr distillation: bp 185–1908C
(0.15 mmHg); [a]24: +1.4 (c 2.15, CHCl3); 1H NMR: d=
7.15–7.30 [m, 5HD, HC(Ar)], 6.48–6.77 [m, 2H, HC(3’),
HC(5’)], 6.48–6.51 [m, 2H, HC(2’), HC(6’)], 3.15 (s, 3H,
OMe), 3.27 [quint, J=5.7 Hz, 1H, HC(5)], 3.15 (br. s, 1H,
NH), 2.62–2.78 [m, 2H, H2C(7)], 1.73–1.86 [m, 2H, H2C(6)],
1.48–1.55 [m, 2H, H2C(4)[, 1.29–1.37 [m, 4H, H2C(3),
CH2C(2)], 0.88 [t, J=6.9 Hz, 3H, H3C(1)]; 13C NMR: d=
151.63 [C(4’)], 142.34 [C(1’)], 142.34 [C(8)], 128.48 [C(10),
C(12)], 128.39 [C(9), C(13)], 125.81 [C(11)], 114.98 [C(3’),
C(5’)], 114.39 [C(2’), C(6’)], 55.86 (OMe), 53.34 [C(5)],
36.69 [C(7)], 34.69 [C(6)], 32.37 [C(4)], 28.14 [C(3)], 22.92
[C(2)], 14.19 [C(1)]; IR (CCl4): n=3420 (br., w), 3027 (m),
2932 (s), 2852 (m), 2832 (m), 1603 (w), 1512 (s), 1464 (m),
1455 (m), 1441 (m), 1406 (m), 1379 (w), 1242 (s), 1181 (m),
1046 (s), 818 cmÀ1 (s); MS (70 eV): m/z=299 (4), 298 (27),
297 (M+, 76), 240 (M+ÀC4H9, 92), 192 (M+ÀC6H5CH2CH2,
100), 162 (3), 149 (35), 136 (13), 134 (18), 122(10), 117(6),
108 (8), 105 (6), 91 (42), 79 (5), 65 (8); chiral HPLC tR (S)-
19, 20.36 (4.5%); tR (R)-19, 23.33 (95.5%) (Diacel OD
column; hexane/EtOH, 99.5/0.5, 0.5 mLminÀ1); anal. calcd.
for C20H27NO (297.44): C 80.76, H 9.15, N 4.71; found: C
80.89, H 9.10, N, 4.71.
(R)-N-(4-Methoxyphenyl)-a-
methylbenzenepropenACHTREaUGN mine (17). Stoichiometric with
12bc (Table 5, entry 2)
To a solution of 12bc (649 mg, 2.01 mmol) in toluene
(20 mL) in a flame-dried, 250-mL, 3-necked, round-bottom
flask equipped with a stir bar, a thermometer, a septum and
a nitrogen inlet was added MeLi (2.70 mL, 1.50m in Et2O,
4.0 mmol) at À638C. The resulting mixture was stirred for
30 min, and a toluene solution (10 mL) of imine 10 (526 mg,
2.01 mmol) was added over a period of 5 min. The remain-
ing imine was washed in 5 mL of toluene, twice. This yellow
solution was stirred for 1 h at À638C and quenched with
MeOH (2 mL) at that temperature. The reaction mixture
was warmed to room temperature, and diluted with TBME
(20 mL) and water (10 mL). The mixture was extracted with
TBME (350 mL). The combined organic layers were
washed with brine (200 mL) and then dried over Na2SO4.
Concentration followed by SiO2 column chromatography
(hexane/EtOAc, 20:1) afforded the amine 17 (yield: 394 mg,
79%) as a yellow oil and 12bc (yield: 602 mg, 91%) was re-
covered by continued elution (hexane/EtOAc, 3:1). An ana-
lytical sample of 17 was obtained after Kugelrohr distilla-
tion: bp 210–2208C (0.4 mmHg); [a]2D4: +110.1 (c 1.05,
1
CHCl3); H NMR: d=7.19–7.37 [m, 5H, HC(Ar)], 6.74–6.78
[m, 2H, HC(3’), HC(5’)], 6.61–6.65 [m, 2H, HC(2’),
1042
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 1023 – 1045