S. Bräse et al.
6.03 mmol) and TiCl4 (2.61mmol of a 1 m solution in dichloromethane)
were added. The reaction mixture was refluxed in a Dean–Stark appara-
tus for 40 h. After removal of the solvent under reduced pressure, the di-
astereomers were separated and purified by flash chromatography. The
first band gave the RP,S diastereomer (0.31g, 35%) as an orange-red
solid. Rf =0.35 (pentane/diethyl ether=9:1); m.p. 1628C; [a]2D0 =+630
(c=0.33, CHCl3); 1H NMR (500 MHz, CDCl3): d 0.98–1.07 (m, 1H),
1.10–1.20 (m, 2H), 1.31–1.38 (m, 1H), 1.49 (d, J=6.4 Hz, 3H), 1.54–1.75
(m, 7H), 2.19–2.27 (m, 1H), 2.30–2.37 (m, 1H), 2.55 (ddd, J=10.8, 4.8,
2.3 Hz, 1H), 2.86 (dd, J=13.1, 9.61 Hz, 1H), 3.03 (ddd, J=10.8, 4.8,
2.7 Hz, 1H), 3.10–3.15 (m, 1H), 3.20–3.26 (m, 1H), 3.39 (quin, J=6.5 Hz,
1H), 3.51 (ddd, J=10.4, 5.1, 2.7 Hz, 1H), 6.01 (d, J=7.3 Hz, 1H), 6.44–
6.49 (m, 3H), 6.54–6.60 (m, 2H), 7.07–7.12 (m, 1H), 7.43–7.51 (m, 3H),
7.59–7.63 ppm (m, 1H); 13C NMR (125 MHz, CDCl3): d=20.57, 26.08,
26.14, 26.18, 29.06, 29.62, 30.27, 33.95, 35.47, 36.50, 44.40, 58.67, 124.87,
126.93, 128.75, 129.03, 129.73, 130.03, 130.07, 131.11, 133.02, 135.94,
136.81, 137.90, 139.93, 143.38, 168.24, 170.46 ppm; IR (KBr): n˜ =3029
(w), 3007 (w), 2928 (m), 2852 (m), 1892 (w), 1732 (w), 1561 (m), 1437
(m), 1238 cmÀ1 (w); MS (70 eV, EI): m/z (%): 437 (1) [M+], 278 (2), 223
(9), 149 (100), 120 (2), 105 (3), 71 (2), 57 (5), 43 (1); HRMS-EI: m/z
calcd for C31H35NO: 437.2718; found: 437.2715. The second band gave
the SP,S diastereomer (0.36 g, 41%) as an orange-red solid. Rf =0.24
(pentane/diethyl ether=9:1); m.p. 1308C; [a]2D0 =À878 (c=0.47 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=0.93 (d, J=6.5 Hz, 3H), 1.20–
1.48 (m, 6H), 1.63–1.71 (m, 2H), 1.79 (d, J=12.2 Hz, 1H), 1.89 (d, J=
12.2 Hz, 1H), 1.97 (d, J=12.2 Hz, 1H), 2.13 (d, J=12.2 Hz, 1H), 2.20–
2.27 (m, 1H), 2.31–2.40 (m, 1H), 2.55 (ddd, J=10.9, 5.0, 1.7 Hz, 1H),
2.87 (dd, J=13.1, 9.9 Hz, 1H), 3.01–3.08 (m, 1H), 3.21 (ddd, J=10.9, 5.2,
2.4 Hz, 1H), 3.46–3.60 (m, 2H), 5.99 (d, J=7.3 Hz, 1H), 6.42–6.49 (m,
3H), 6.55 (dd, J=7.7, 1.3 Hz 1H), 7.07 (dd, J=7.7, 1.8 Hz, 1H), 7.20–
7.35 (m, 2H), 7.42 À7.55 ppm (m, 3H); 13C NMR (125 MHz, CDCl3): d=
19.26, 26.50, 26.52, 26.67, 29.62, 30.16, 30.36, 33.89, 35.43, 36.33, 44.09,
57.75, 120.43, 124.67, 126.87, 129.27, 129.87, 130.50, 131.15, 133.10, 135.31,
136.94, 137.86, 139.96, 143.24, 168.81, 170.72 ppm; IR (KBr): n˜ =3029
(w), 3007 (w), 2928 (m), 2853 (m), 1892 (w), 1730 (w), 1564 (m), 1437
(m), 1238 cmÀ1 (w); MS (70 eV, EI): m/z (%): 437 (100) [M+], 333 (8),
222 (53), 194 (10), 149 (20), 111 (29), 69 (23), 43 (3); HRMS-EI: m/z
calcd for C31H35NO: 437.2718; found: 437.2722.
7.4, 2.2 Hz, 2H), 6.59 (dd, J=7.8, 1.5 Hz, 1H), 6.65 (dd, J=7.6, 1.7 Hz,
1H), 7.00 (dd, J=7.7, 1.7 Hz, 1H), 7.32–7.38 (m, 2H), 7.40–7.55 (m, 6H),
7.63 ppm (d, J=7.6 Hz, 1H); 13C NMR (125 MHz, CDCl3): d=30.07,
30.70, 33.93, 35.56, 35.95, 36.46, 63.46, 120.83, 123.56, 125.06, 125.44,
126.87, 127.16, 127.74, 128.56, 129.36, 129.64, 130.25, 131.31, 133.09,
135.69, 137.02, 137.88, 139.92, 143.50, 144.65, 166.32, 171.10 ppm; IR
(KBr): n˜ =3453 (w), 3025 (w), 2989 (w), 2925 (m), 2850 (w), 1876 (w),
1554 (m), 1438 (m), 1253 ppm (w); MS (70 eV, EI): m/z (%): 443 (37)
[M+], 339 (7), 328 (12), 222 (42), 149 (100), 117 (52), 71 (25), 57 (35), 43
(21); HRMS-EI: m/z calcd for C32H29NO: 443.2249; found: 443.2248.
Synthesis of (RP,S)- and (SP,S)-12g: Racemic 5-benzoyl-4-hydroxy-
[2.2]paracyclophane (3; 0.30 g, 0.91mmol) was dissolved in toluene
(100 mL) under argon, and (S)-3,3-dimethyl-2-aminobutane (0.28 g,
2.73 mmol) and TiCl4 (1.18 mmol of a 1m solution in dichloromethane)
were added. The reaction mixture was refluxed in a Dean–Stark appara-
tus for 40 h. After removal of the solvent under reduced pressure, the di-
astereomers were separated and purified by flash chromatography. The
first band gave the RP,S diastereomer (0.10 g, 28%) as an orange solid.
Rf =0.37 (pentane/diethyl ether=9:1); m.p. 1828C; [a]2D0 =+1163 (c=
1
0.13 in CHCl3); H NMR (500 MHz, CDCl3): d=0.83 (s, 9H), 1.46 (d, J=
6.6 Hz, 3H), 1.68 (dd, J=13.9, 9.2 Hz, 1H), 2.17–2.25 (m, 1H), 2.29–2.36
(m, 1H), 2.57 (ddd, J=10.8, 4.6, 1.8 Hz, 1H), 2.86 (dd, J=12.8, 9.4 Hz,
1H), 3.02 (ddd, J=10.8, 4.5, 2.9 Hz, 1H), 3.24 (ddd, J=10.3, 5.0, 2.4 Hz,
1H), 3.32–3.38 (m, 1H), 3.49–3.56 (m, 1H), 5.99 (d, J=7.3 Hz, 1H), 6.46
(dd, J=7.7, 1.7 Hz, 3H), 6.56 (dd, J=7.7, 1.7 Hz, 1H), 7.07 (dd, J=7.8,
1.8 Hz, 1H), 7.40–7.54 ppm (m, 4H); 13C NMR (125 MHz, CDCl3): d=
18.10, 26.38, 30.09, 33.95, 34.00, 35.51, 36.58, 62.61, 120.04, 125.05, 126.94,
129.29, 129.68, 130.15, 131.15, 133.01, 136.04, 136.81, 137.91, 140.02,
143.41, 167.78, 170.53 ppm; IR (KBr): n˜ =3436 (w), 3011 (w), 2964 (m),
2928 (m), 2869 (w), 1892 (w), 1559 (m), 1438 (m), 1242 cmÀ1 (s); MS
(70 eV, EI): m/z (%): 411 (5) [M+], 307 (2), 223 (3), 85 (3), 58 (39), 43
(100); HRMS-EI: m/z calcd for C29H33NO: 411.2562; found: 411.2566.
The second band gave the SP,S diastereomer (0.13 g, 34%) as an orange-
red solid. Rf =0.31(pentane/diethyl ether =9:1); m.p. 2068C; [a]2D0 =À420
(c=0.34 in CHCl3); 1H NMR (500 MHz, CDCl3): d=0.83 (d, J=6.6 Hz,
3H), 1.19 (s, 9H), 1.73 (dd, J=13.8, 9.5 Hz, 1H), 2.19–2.27 (m, 1H),
2.34–2.44 (m, 1H), 2.51–2.62 (m, 1H), 2.83–2.91 (m, 1H), 3.06 (dt, J=
10.7, 2.5 Hz, 1H), 3.25 (ddd, J=12.6, 10.2, 4.8 Hz, 1H), 3.47–3.59 (m,
2H), 6.02 (d, J=7.9 Hz, 1H), 6.46 (dt, J=7.5, 1.9 Hz, 4H), 6.56 (dd, J=
7.9, 1.9 Hz, 1H), 7.07 (dd, J=7.5, 1.9 Hz, 1H), 7.44–7.58 ppm (m, 4H);
13C NMR (125 MHz, CDCl3): d=16.93, 26.99, 30.35, 33.92, 34.05, 35.46,
36.28, 61.88, 120.86, 124.89, 126.92, 129.16, 130.78, 131.20, 133.12, 135.51,
136.91, 137.90, 140.03, 143.24, 170.89 ppm; IR (KBr): n˜ =3457 (w), 2965
(m), 2926 (m), 1869 (w), 1829 (w), 1558 (m), 1438 (m), 1241 cmÀ1 (s); MS
(70 eV, EI): m/z (%): 411 (5) [M+], 307 (3), 223 (3), 58 (39), 43 (100);
HRMS-EI: m/z calcd for C29H33NO: 411.2562; found: 411.2566.
Synthesis of (RP,S)- and (SP,S)-12c: Racemic 5-benzoyl-4-hydroxy-
[2.2]paracyclophane (3; 0.11 g, 0.33 mmol) was dissolved in of toluene
(50 mL) under argon, and (S)-indan-1-ylamine (C; 0.13 g, 1.00 mmol) and
TiCl4 (0.44 mmol of a 1m solution in dichloromethane) were added. The
reaction mixture was refluxed in a Dean–Stark apparatus for 40 h. After
removal of the solvent under reduced pressure, the diastereomers were
separated and purified by flash chromatography. The first band gave the
RP,S diastereomer (61mg, 42%) as an orange solid. Rf =0.33 (pentane/di-
ethyl ether=9:1); m.p. 1408C; [a]2D0 =+1347 (c=0.12 in CHCl3);
1H NMR (500 MHz, CDCl3): d=1.86 (dd, J=13.6, 9.5 Hz, 1H), 2.25–2.33
(m, 1H), 2.37–2.45 (m, 1H), 2.49–2.59 (m, 2H), 2.66–2.74 (m, 1H), 2.90
(dd, J=13.1, 9.5 Hz, 1H), 2.96–3.04 (m, 2H), 3.10–3.17 (m, 1H), 3.20–
3.28 (m, 1H), 3.40–3.47 (m, 1H), 5.08 (t, J=7.7 Hz, 1H), 6.10 (d, J=
7.5 Hz, 1H), 6.45 (dd, J=7.6, 1.8 Hz, 1H), 6.49 (d, J=7.6 Hz, 1H), 6.51–
6.58 (m, 2H), 6.97 (d, J=7.5 Hz, 1H), 7.04 (dd, J=7.8, 1.9 Hz, 1H), 7.14
(t, J=7.6 Hz, 1H), 7.22 (t, J=7.2 Hz, 1H), 7.28 (d, J=7.5 Hz, 1H), 7.35–
7.47 (m, 2H), 7.46–7.54 (m, 3H), 16.16 ppm (brs, 1H); 13C NMR
(125 MHz, CDCl3): d=30.24, 30.93, 33.87, 35.43, 36.39, 36.39, 63.74,
120.60, 122.99, 123.98, 124.59, 125.63, 126.88, 127.00, 127.69, 128.29,
129.16, 129.52, 129.86, 131.31, 133.09, 136.12, 136.79, 137.91, 139.91,
142.32, 143.36, 165.07, 171.93 ppm; IR (KBr): n˜ =3438 (w), 3067 (w),
2995 (m), 2942 (m), 2849 (w), 2468 (w), 1882 (w), 1561 (m), 1441 (m),
1247 cmÀ1 (m); MS (70 eV, EI): m/z (%): 443 (100) [M+], 339 (14), 328
(29), 222 (93), 117 (93), 58 (14), 43 (56); HRMS-EI: m/z calcd for
C32H29NO: 443.2249; found: 443.2248. The second band gave the SP,S dia-
stereomer (69 mg, 47%) as an orange-red solid. Rf =0.27 (pentane/dieth-
yl ether=9:1); m.p. 1238C; [a]2D0 =À342 (c=0.23 in CHCl3); 1H NMR
(500 MHz, CDCl3): d=1.86 (dd, J=14.0, 9.5 Hz, 1H), 2.06–2.14 (m, 1H),
2.16–2.24 (m, 1H), 2.28–2.35 (m, 1H), 2.46–2.60 (m, 2H), 2.76–2.84 (m,
1H), 2.90–2.93 (m, 1H), 2.94–3.06 (m, 2H), 3.11–3.19 (m, 1H), 3.40–3.44
(m, 1H), 5.19 (t, J=7.9 Hz, 1H), 6.08 (d, J=7.5 Hz, 1H), 6.48 (dd, J=
Synthesis of (RP,S)- and (SP,S)-12h: Racemic 5-benzoyl-4-hydroxy-
[2.2]paracyclophane (3; 0.21g, 0.63 mmol) was dissolved in toluene
(100 mL) under argon, and (S)-1-naphthyl-1-ylethylamine (0.33 g,
1.90 mmol) and TiCl4 (0.82 mmol of a 1m solution in dichloromethane)
were added. The reaction mixture was refluxed in a Dean–Stark appara-
tus for 40 h. After removal of the solvent under reduced pressure, the di-
astereomers were separated and purified by flash chromatography. The
first band gave the SP,S diastereomer (0.15 g, 48%) as an orange solid.
Rf =0.14 (pentane/ethyl acetate=19:1); m.p. 1768C; [a]2D0 =À198 (c=0.55
in CHCl3); 1H NMR (500 MHz, CDCl3): d=1.65 (d, J=6.4 Hz, 3H),
1.68–1.72 (m, 1H), 2.05–2.12 (m, 1H), 2.18–2.25 (m, 1H), 2.63 (ddd, J=
12.7, 11.0, 4.9 Hz, 1H), 2.72 (dd, J=12.7, 9.9 Hz, 1H), 3.15 (ddd, J=12.7,
10.3, 2.3 Hz, 1H), 3.37 (ddd, J=12.7, 10.5, 4.7 Hz, 1H), 3.61 (ddd, J=
12.7, 10.3, 2.3 Hz, 1H), 5.51 (q, J=6.4 Hz, 1H), 6.11 (d, J=7.5 Hz, 1H),
6.19 (dd, J=7.6, 1.5 Hz, 1H), 6.47–6.56 (m, 3H), 7.05–7.15 (m, 3H), 7.33
(dd, J=7.4, 1.1 Hz, 2H), 7.46 (t, J=7.4 Hz, 1H), 7.52 (dt, J=8.4, 1.1 Hz,
1H), 7.57 (t, J=7.0 Hz, 1H), 7.72 (t, J=7.8 Hz, 1H), 7.82 (d, J=8.2 Hz,
1H), 7.90 (d, J=8.0 Hz, 1H), 7.99 (d, J=8.2 Hz, 1H), 8.17 ppm (d, J=
7.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): d=25.63, 30.38, 34.00, 35.27,
36.37, 55.06, 120.93, 122.62, 123.80, 125.61, 125.73, 126.05, 126.17, 126.89,
127.70, 129.20, 129.29, 129.45, 129.66, 130.57, 131.34, 133.15, 134.17,
135.81, 137.11, 138.03, 139.87, 141.97, 143.64, 166.11, 171.09 ppm; IR
(KBr): n˜ =3045 (w), 2969 (w), 2930 (m), 2851 (w), 1886 (w), 1740 (m),
4520
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 4509 – 4525