Angewandte
Chemie
Tetrahedron Lett. 1996, 37, 4791 – 4794; e) D. B. Berkowitz, S.
Choi, J.-H. Maeng, J. Org. Chem. 2000, 65, 847 – 860.
[5]Reviews: a) M. Reuman, A. I. Meyers, Tetrahedron 1985, 41,
837 – 860; b) T. G. Gant, A. I. Meyers, Tetrahedron 1994, 50,
2297 – 2360; c) A. I. Meyers, J. Heterocycl. Chem. 1998, 35, 991 –
1002.
[6]These amino alcohols are commercially available or can be
synthesized (K. Drauz, W. Jahn, M. Schwarm, Chem. Eur. J.
1995, 1, 538 – 540). However, we thank Degussa AG, Germany,
for the generous gift of the auxiliaries 4.
[7]T. Linker, F. Rebien, G. Tóth, A. Simon, J. Kraus, G. Bringmann,
Chem. Eur. J. 1998, 4, 1944 – 1951.
[8]Selected analytical data of key intermediates: 1,2-dihydronaph-
thalene 6: m.p. 118–1208C; [a]3D1 = À189.5 (c = 1.01, CHCl3);
1H NMR (300 MHz, CDCl3): d = 3.58 (ddd, J = 8.5, 4.5, 2.0 Hz,
1H, H-2), 3.64 (s, 3H, CO2Me), 3.79 (s, 6H, OMe-3’), 3.83 (s, 3H,
OMe-4’), 4.43 (d, J = 8.5 Hz, 1H, H-1), 5.81 (dd, J = 9.5, 4.5 Hz,
1H, H-3), 5.90–5.96 (m, 2H, OCH2O), 6.41 (s, 2H, H-2’), 6.42 (s,
1H, H-8), 6.50 (dd, J = 9.5, 2.0 Hz, 1H, H-4), 6.64 ppm (s, 1H, H-
5); 13C NMR (75 MHz, CDCl3): d = 46.1 (d, C-1), 48.4 (d, C-2),
52.1 (q, CO2Me), 56.0 (q, OMe-3’), 60.7 (q, OMe-4’), 100.9 (t,
OCH2O), 105.4 (d, C-2’), 106.9 (d, C-5), 109.2 (d, C-8), 121.7 (d,
C-3), 126.4 (s, C-4a), 128.6 (d, C-4), 130.2 (s, C-8a), 136.8 (s, C-4’),
138.5 (s, C-1’), 146.4 (s, C-7), 147.2 (s, C-6), 153.1 (s, C-3’),
173.6 ppm (s, CO); elemental analysis calcd for C22H22O7: C
66.32, H 5.57; found: C 66.31, H 5.56. Allylic alcohol 8a:
m.p. 1638C; [a]2D0 = + 104.8 (c = 1.0, CHCl3, 96% ee); H NMR
1
(300 MHz, CDCl3): d = 2.17 (d, J = 10.2 Hz, 1H, OH), 3.74 (s,
3H, CO2Me), 3.78 (s, 9H, 3OMe), 4.93 (d, J = 3.7 Hz, 1H, H-1),
5.34 (ddd, J = 10.2, 3.7, 2.8 Hz, 1H, H-4), 5.91–5.95 (m, 2H,
OCH2O), 6.30 (s, 2H, H-2’), 6.65 (s, 1H, H-8), 7.13 (s, 1H, H-5),
7.20 ppm (d, J = 2.8 Hz, 1H, H-3); 13C NMR (75 MHz, CDCl3):
d = 45.6 (d, C-1), 51.9 (q, CO2Me), 55.9 (q, OMe-3’), 60.6 (q,
OMe-4’), 65.6 (d, C-4), 101.0 (t, OCH2O), 104.8 (d, C-2’), 106.3
(d, C-5), 107.6 (d, C-8), 128.7, 130.0, 132.3, 136.3 (4 s, C-2, C-4a,
C-8a, C-4’), 138.9 (s, C-1’), 139.4 (d, C-3), 146.8, 147.4 (2 s, C-6,
C-7), 153.0 (s, C-3’), 166.3 ppm (s, CO); elemental analysis calcd
for C22H22O8: C 63.76, H 5.35; found: C 63.53, H 5.56. (À)-
Epipodophyllotoxin (1a): m.p. 1808C (Ref.:[4b] 1828C); [a]D31
=
À88.4 (c = 0.52, CHCl3, 97% ee) (Ref.:[4b] [a]D31 = À72.0 (c = 0.70,
1
CHCl3, 98% ee)); H NMR (500 MHz, CDCl3): d = 1.81 (d, J =
4.3 Hz, 1H, OH), 2.84 (dddd, J = 14.1, 10.6, 7.9, 3.4 Hz, 1H, H-
3), 3.29 (dd, J = 14.1, 5.1 Hz, 1H, H-2), 3.74 (s, 6H, OMe-3’), 3.80
(s, 3H, OMe-4’), 4.36 (dd, J = 10.6, 8.5 Hz, 1H, OCHaHbC), 4.39
(dd, J = 8.5, 7.9 Hz, 1H, OCHaHbC), 4.62 (d, J = 5.1 Hz, 1H, H-
1), 4.88 (dd, J = 4.3, 3.4 Hz, 1H, H-4), 5.98 (d, J = 1.3 Hz, 1H,
OCHaHbO), 6.00 (d, J = 1.3 Hz, 1H, OCHaHbO), 6.28 (s, 2H, H-
2’), 6.56 (s, 1H, H-8), 6.88 ppm (s, 1H, H-5); 13C NMR
(125 MHz, CDCl3): d = 36.3 (d, C-3), 40.5 (d, C-2), 43.8 (d, C-
1), 56.3 (q, OMe-3’), 60.8 (q, OMe-4’), 66.9 (d, C-4), 67.6 (t,
CH2OH), 101.6 (t, OCH2O), 108.2 (d, C-2’), 108.9 (d, C-5), 110.5
(d, C-8), 131.8, 132.0 (2s, C-4a, C-8a), 135.0 (s, C-4’), 137.2 (s, C-
1’), 147.5, 148.6 (2s, C-6, C-7), 152.6 (s, C-3’), 175.0 ppm (s, CO).
[9]A. I. Meyers, B. A. Barner, J. Org. Chem. 1986, 51, 120 – 122.
[10]T. Linker, F. Rebien, G. Tóth, Chem. Commun. 1996, 2585 –
2586.
[11]a) W. Adam, R. Curci, J. O. Edwards, Acc. Chem. Res. 1989, 22,
205 – 211; b) W. Adam, J. Bialas, L. Hadjiarapoglou, Chem. Ber.
1991, 124, 2377.
[12]T. Linker, K. Peters, E.-M. Peters, F. Rebien, Angew. Chem.
1996, 108, 2662 – 2664; Angew. Chem. Int. Ed. Engl. 1996, 35,
2486 – 2489.
[13]Reviews: a) M. Bols, T. Skrydstrup, Chem. Rev. 1995, 95, 1253 –
1277; b) L. Fensterbank, M. Malacria, S. M. Sieburth, Synthesis
1997, 813 – 854.
[14]Review: G. R. Jones, Y. Landais, Tetrahedron 1996, 52, 7599 –
7662.
Angew. Chem. Int. Ed. 2003, 42, 2487 – 2489
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2489