C. Bolm et al.
hyde (1 f, 0.054 g, 0.4 mmol), o-methoxyaniline (0.049 g, 0.4 mmol,
1.0 equiv)and phenylacetylene (0.123 g, 1.2 mmol, 3.0 equiv). Purification
by flash column chromatography (n-pentane/diethyl ether 10:1)afforded
pure (À)-4k (0.071 g, 0.21 mmol, 52%)as a yellow oil that solidified
upon standing. [a]2D0 =À89.1 (c=0.60, CHCl3); HPLC (Chiralcel OD-H,
254 nm, heptane/iPrOH 98:2, flow rate=0.6 mLminÀ1): tr (À, major)=
13.6 min, tr (+, minor)=15.5 min; ee=87%; 1H NMR (300 MHz,
CDCl3): d=3.85 (s, 3H), 3.86 (s, 3H), 4.74 (d, J=5.5 Hz, 1H), 5.47 (d,
J=5.5 Hz, 1H), 6.73–6.85 (m, 2H), 6.88–7.00 (m, 4H), 7.27–7.35 (m,
3H), 7.40–7.48 (m, 2H), 7.57–7.66 (m, 2H); 13C NMR (75 MHz, CDCl3):
d=49.8, 55.36, 55.41, 84.6, 89.0, 109.6, 111.7, 114.1, 117.6, 121.1, 123.0,
128.2, 128.2, 128.6, 131.8, 132.1, 136.5, 147.2, 159.4; IR (KBr): n˜ =3426,
2944, 1601, 1508, 1451, 1243, 1220, 1169 cmÀ1; MS (EI, 70 eV): m/z: 343
[M]+, 236, 221 [MÀC7H8NO]+, 206, 178, 152, 92, 77; elemental analysis
calcd (%)for C 23H21NO (343.42): C 80.44, H 6.16, N 4.08; found: C
80.43, H 6.00, N 4.16.
(À)-N-(2-Methoxyphenyl)-3-amino-3-(2-naphthyl)-1-phenylprop-1-yne
(4o): Prepared according to GP 4 starting from 2-naphthaldehyde (1j,
0.062 g, 0.4 mmol), o-methoxyaniline (0.049 g, 0.4 mmol, 1.0 equiv)and
phenylacetylene (0.123 g, 1.2 mmol, 3.0 equiv). Purification by flash
column chromatography (n-pentane/diethyl ether 18:1)afforded pure
(À)-4o (0.113 g, 0.31 mmol, 78%)as a yellow oil that solidified upon
standing. [a]2D0 =À69.9 (c=0.85, CHCl3); HPLC (Chiralcel OD-H,
254 nm, heptane/iPrOH 95:5, flow rate=0.6 mLminÀ1): tr (+, minor)=
1
11.4 min, tr (À, major)=16.1 min; ee=81%; H NMR (400 MHz, CDCl3):
d=3.76 (s, 3H), 4.80 (brs, 1H), 5.58 (s, 1H), 6.63–6.82 (m, 4H), 7.17–
7.24 (m, 3H), 7.32–7.44 (m, 4H), 7.67 (dd, J=8.7, 1.7 Hz, 1H), 7.74–7.83
(m, 3H), 8.05 (s, 1H); 13C NMR (100 MHz, CDCl3): d=50.7, 55.5, 85.2,
88.7, 109.6, 111.7, 117.8, 121.1, 122.9, 125.4, 126.1, 126.2, 127.7, 128.15,
128.21, 128.3, 128.6, 131.8, 133.1, 133.4, 136.5, 137.3, 147.2; IR (neat): n˜ =
3391, 2936, 2854, 1598, 1505, 1455, 1235, 1123, 1026 cmÀ1; MS (EI,
70 eV): m/z: 363 [M]+, 241 [MÀC7H8NO]+, 226, 139, 115, 77; elemental
analysis calcd (%)for C 26H21NO (363.45): C 85.92, H 5.82, N 3.85; found:
C 86.14, H 5.99, N 3.92.
(À)-N-(2-Methoxyphenyl)-3-amino-3-(3-methoxyphenyl)-1-phenylprop-1-
yne (4l): Prepared according to GP 4 starting from m-methoxybenzalde-
hyde (1g, 0.054 g, 0.4 mmol), o-methoxyaniline (0.049 g, 0.4 mmol,
1.0 equiv)and phenylacetylene (0.123 g, 1.2 mmol, 3.0 equiv). Purification
by flash column chromatography (n-pentane/diethyl ether 15:1)afforded
pure (À)-4l (0.111 g, 0.32 mmol, 81%)as a yellow oil. [ a]2D0 =À75.2 (c=
0.94, CHCl3); HPLC (Chiralcel OD-H, 254 nm, heptane/iPrOH 95:5,
flow rate=0.6 mLminÀ1): tr (+, minor)=10.6 min, tr (À, major)=
(À)-N-(2-Methoxyphenyl)-3-amino-3-(1-naphthyl)-1-phenylprop-1-yne
(4p): Prepared according to GP 4 starting from 1-naphthaldehyde (1k,
0.062 g, 0.4 mmol), o-methoxyaniline (0.049 g, 0.4 mmol, 1.0 equiv)and
phenylacetylene (0.123 g, 1.2 mmol, 3.0 equiv). Purification by flash
column chromatography (n-pentane/diethyl ether 13:1)afforded pure
(À)-4p (0.090 g, 0.25 mmol, 62%)as a yellow oil. [ a]2D0 =À48.7 (c=0.96,
CHCl3); HPLC (Chiralcel OD-H, 254 nm, heptane/iPrOH 98:2, flow
rate=0.6 mLminÀ1): tr (+, minor)=13.0 min, tr (À, major)=14.9 min;
ee=86%; 1H NMR (400 MHz, CDCl3): d=3.70 (s, 3H), 4.78 (brs, 1H),
6.04 (s, 1H), 6.65–6.75 (m, 2H), 6.77–6.88 (m, 2H), 7.16–7.22 (m, 3H),
7.30–7.37 (m, 3H), 7.39–7.48 (m, 2H), 7.77 (d, J=8.5 Hz, 1H), 7.80–7.85
(m, 1H), 7.93 (d, J=6.9 Hz, 1H), 8.10–8.16 (m, 1H); 13C NMR
(100 MHz, CDCl3): d=48.1, 55.5, 85.3, 88.6, 109.6, 111.3, 117.6, 121.2,
123.0, 123.7, 125.4, 125.5, 125.8, 126.5, 128.18, 128.21, 128.8, 129.0, 130.9,
131.8, 134.1, 134.6, 136.5, 147.1; IR (neat): n˜ =3417, 3055, 2937, 2838,
1598, 1509, 1453, 1232, 1125, 1030 cmÀ1; MS (EI, 70 eV): m/z: 363 [M]+,
241 [MÀC7H8NO]+, 226, 115, 92, 65; elemental analysis calcd (%)for
C26H21NO (363.45): C 85.92, H 5.82, N 3.85; found: C 85.64, H 5.88, N
3.82.
1
14.0 min; ee=88%; H NMR (400 MHz, CDCl3): d=3.84 (s, 3H), 3.85 (s,
3H), 4.79 (brs, 1H), 5.48 (s, 1H), 6.73–6.78 (m, 1H), 6.80–6.93 (m, 5H),
7.23–7.37 (m, 6H), 7.39–7.47 (m, 2H); 13C NMR (100 MHz, CDCl3): d=
50.5, 55.4, 55.5, 84.8, 88.7, 109.6, 111.6, 113.0, 113.5, 117.7, 119.7, 121.1,
122.9, 128.17, 128.21, 129.7, 131.8, 136.4, 141.5, 147.1, 159.9; IR (neat):
n˜ =3418, 3060, 2937, 1600, 1511, 1490, 1456, 1432, 1249, 1124, 1032 cmÀ1
;
MS (EI, 70 eV): m/z: 343 [M]+, 312, 236 [MÀC7H7O]+, 221
[MÀC7H8NO]+, 178, 120, 77; HRMS (EI): m/z: calcd for C23H21NO2:
343.1572; found: 343.1572.
(À)-N-(2-Methoxyphenyl)-3-amino-3-(2-methoxyphenyl)-1-phenylprop-1-
yne (4m): Prepared according to GP 4 starting from o-methoxybenzalde-
hyde (1h, 0.054 g, 0.4 mmol), o-methoxyaniline (0.049 g, 0.4 mmol,
1.0 equiv)and phenylacetylene (0.123 g, 1.2 mmol, 3.0 equiv). Purification
by flash column chromatography (n-pentane/diethyl ether 25:1)afforded
pure (À)-4m (0.115 g, 0.34 mmol, 84%)as a yellow oil. [ a]2D0 =À52.7 (c=
0.63, CHCl3); HPLC (Chiralcel OD, 254 nm, heptane/iPrOH 99.5:0.5,
flow rate=0.6 mLminÀ1): tr (À, major)=27.6 min, tr (+, minor)=
(À)-N-(2-Methoxyphenyl)-3-amino-3-[2-(5-bromo)thienyl]-1-phenylprop-
1-yne (4q): Prepared according to GP 4 starting from 5-bromo-2-thieny-
laldehyde (1l, 0.077 g, 0.4 mmol), o-methoxyaniline (0.049 g, 0.4 mmol,
1.0 equiv)and phenylacetylene (0.123 g, 1.2 mmol, 3.0 equiv). Purification
by flash column chromatography (n-pentane/diethyl ether 3:1)afforded
pure (À)-4q (0.142 g, 0.36 mmol, 89%)as a yellow oil. [ a]2D0 =À62.5 (c=
0.52, CHCl3); HPLC (Chiralcel OD-H, 254 nm, heptane/iPrOH 95:5,
flow rate=0.6 mLminÀ1): tr (+, minor)=9.5 min, tr (À, major)=
11.6 min; ee=68%; 1H NMR (400 MHz, CDCl3): d=3.86 (s, 3H), 4.87
(d, J=7.6 Hz, 1H), 5.68 (d, J=7.4 Hz, 1H), 6.80–6.88 (m, 4H), 6.95 (d,
J=3.8 Hz, 1H), 7.05 (dd, J=3.8, 1.2 Hz, 1H), 7.26–7.34 (m, 4H), 7.41–
7.44 (m, 1H); 13C NMR (100 MHz, CDCl3): d=46.5, 55.6, 84.7, 87.4,
109.8, 112.1, 118.5, 121.0, 122.3, 125.5, 128.21, 128.23, 128.5, 129.5, 131.7,
135.5, 145.7, 147.3; IR (neat): n˜ =3402, 3059, 2936, 2838, 2237, 1729,
1599, 1508, 1448, 1338, 1241, 1124, 1030 cmÀ1; MS (EI, 70 eV): m/z: 399–
397 [M]+, 320–318, 277–275 [MÀC7H8NO]+, 196–194, 151, 138, 107, 91,
65; elemental analysis calcd (%)for C 20H16NOBrS (398.31): C 60.31, H
4.05, N 3.52; found: C 60.97, H 4.37, N 3.40.
1
35.0 min; ee=97%; H NMR (400 MHz, CDCl3): d=3.74 (s, 3H), 3.80 (s,
3H), 4.73 (brs, 1H), 5.76 (d, J=4.4 Hz, 1H), 6.60–6.66 (m, 1H), 6.68–
6.72 (m, 1H), 6.75–6.82 (m, 2H), 6.85 (dd, J=8.2, 0.9 Hz, 1H), 6.92 (dt,
J=7.4, 0.9 Hz, 1H), 7.15–7.26 (m, 3H), 7.29–7.35 (m, 2H), 7.62 (dd, J=
7.5, 1.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=44.7, 55.5, 55.8, 83.5,
89.4, 109.5, 111.0, 111.7, 117.4, 120.9, 121.1, 123.2, 128.0, 128.1, 128.2,
128.4, 129.2, 131.8, 136.6, 147.2, 159.6; IR (neat): n˜ =3421, 2934, 1599,
1510, 1458, 1246, 1125, 1028 cmÀ1; MS (EI, 70 eV): m/z: 343 [M]+, 312,
236 [MÀC7H7O]+, 221 [MÀC7H8NO]+, 189, 178, 115, 65; elemental anal-
ysis calcd (%)for C 23H21NO (343.42): C 80.44, H 6.16, N 4.08; found: C
80.73, H 6.54, N 4.06.
(À)-N-(2-Methoxyphenyl)-3-amino-3-(2-bromophenyl)-1-phenylprop-1-
yne (4n): Prepared according to GP 4 starting from o-bromobenzalde-
hyde (1i, 0.074 g, 0.4 mmol), o-methoxyaniline (0.049 g, 0.4 mmol,
1.0 equiv)and phenylacetylene (0.123 g, 1.2 mmol, 3.0 equiv). Purification
by flash column chromatography (n-pentane/diethyl ether 20:1)afforded
pure (À)-4n (0.140 g, 0.36 mmol, 89%)as a yellow oil. [ a]2D0 =À47.2 (c=
1.0, CHCl3); HPLC (Chiralcel OD-H, 254 nm, heptane/iPrOH 95:5, flow
rate=0.6 mLminÀ1): tr (+, minor)=8.8 min, tr (À, major)=10.0 min; ee=
81%; 1H NMR (400 MHz, CDCl3): d=3.78 (s, 3H), 4.78 (brs, 1H), 5.71
(s, 1H), 6.57–6.81 (m, 4H), 7.07–7.40 (m, 5H), 7.50–7.56 (m, 2H), 7.70–
7.76 (m, 2H); 13C NMR (100 MHz, CDCl3): d=50.4, 55.5, 84.7, 87.8,
109.6, 111.5, 117.9, 121.2, 122.7, 123.6, 128.0, 128.2, 128.4, 128.9, 129.5,
131.8, 133.2, 136.1, 139.0, 147.1; IR (neat): n˜ =3417, 3060, 2933, 2835,
1599, 1511, 1455, 1345, 1244, 1127, 1028 cmÀ1; MS (EI, 70 eV): m/z: 393–
391 [M]+, 362–360, 271–269 [MÀC7H8NO]+, 236 [MÀC6H4Br]+, 189;
HRMS (EI): m/z: calcd for C22H18NOBr: 391.0572; found: 391.0572.
(À)-N-(2-Methoxyphenyl)-3-amino-3-(cyclohexyl)-1-phenylprop-1-yne
(4r): Prepared according to GP 4 starting from cyclohexanecarbaldehyde
(1m, 0.045 g, 0.4 mmol), o-methoxyaniline (0.049 g, 0.4 mmol, 1.0 equiv)
and phenylacetylene (0.123 g, 1.2 mmol, 3.0 equiv). Purification by flash
column chromatography (n-pentane/diethyl ether 3:1)afforded pure ( À)-
4r (0.119 g, 0.37 mmol, 93%)as a yellow oil. [ a]2D0 =À105.7 (c=0.70,
CHCl3); HPLC (2Chiralcel OD-H, 254 nm, heptane/iPrOH 99.5:0.5,
flow rate=0.3 mLminÀ1): tr (+, minor)=48.2 min, tr (À, major)=
52.2 min; ee=85%; 1H NMR (300 MHz, CDCl3): d=1.05–1.35 (m, 5H),
1.60–1.74 (m, 4H), 1.79–1.93 (m, 2H), 3.78 (s, 3H), 4.11 (d, J=5.7 Hz,
1H), 4.41 (brs, 1H), 6.59–6.67 (m, 1H), 6.69–6.78 (m, 2H), 6.79–6.86 (m,
1H), 7.15–7.22 (m, 3H), 7.28–7.34 (m, 2H); 13C NMR (75 MHz, CDCl3):
d=26.1, 26.2, 26.5, 28.8, 30.2, 42.4, 51.5, 55.5, 83.6, 89.3, 109.6, 111.2,
2598
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2587 – 2600