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Rapid Access to ( )-Sedamine and Analogues
2461
Compound ( )-10a
White solid; yield: 1.5g (8%); mp 97.2 °C.
13C NMR (75 MHz, CDCl3): d = 147.48 (CAr), 145.55 (CAr), 144.58
(CAr), 130.04 (2 CAr), 128.27 (2 CAr), 127.56 (CAr), 127.14 (CAr),
125.52 (2 CAr), 125.28 (C4), 123.87 (2 CAr), 75.17 (CHOH), 59.49
(C2), 56.59 (CH2Ar), 41.39 (CH2CHOH), 41.04 (C6), 18.72 (C5).
HRMS (CI): m/z [M + H+] calcd for C20H23N2O3: 339.1710; found:
339.1709.
1H NMR (300 MHz, CDCl3): d = 7.38–7.22 (m, 5 H, HAr), 5.89 (m,
1 H, H4), 5.46 (m, 1 H, H3), 4.92 (dd, J = 7.56, 1.74 Hz, 1 H,
CHOH), 3.08 (m, 1 H, H2), 2.87 (m, 1 H, H6), 2.46 (s, 3 H, NCH3),
2.35–2.29 (m, 2 H, H5, H6), 2.06 (ddd, J = 15.81, 7.59, 2.79, Hz, 1
H, CH2CHOH), 1.97 (m, 1 H, H5), 1.58 (ddd, J = 11.01, 3.03, 1.86
Hz, 1 H, CH2CHOH).
13C NMR (75 MHz, DMSO-d6): d = 145.31 (CAr), 128.31 (CAr),
128.17 (2 CAr), 126.99, 126.78 (C3, C4), 125.60 (2 CAr), 71.89
(CHOH), 61.38 (C2), 51.28 (CH2), 43.31 (NCH3), 39.98 (CH2),
24.79 (CH2).
( )-(1S)-2-[(2R)-1-(4-Fluorobenzyl)-1,2,5,6-tetrahydropyridin-
2-yl]-1-phenylethanol [( )-9e]
Following the general procedure and starting from 6e (1.5 g, 3.9
mmol), column chromatography (CH2Cl2–Et2O, 95:5 to 80:20) af-
forded ( )-9e (0.71 g, 60%) as a colorless oil; ratio ( )-9e/( )-10e,
87:13; Rf = 0.54 (CH2Cl2–MeOH, 99:1).
( )-(1S)-2-[(2R)-1-Benzyl-1,2,5,6-tetrahydropyridin-2-yl]-1-
phenylethanol [( )-9b]
Following the general procedure and starting from 6b (2.5 g, 6.75
mmol), column chromatography (CH2Cl2–Et2O, 95:5) afforded ( )-
9b (1.2 g, 60%) as a colorless oil which rapidly turned brown;
Rf = 0.66 (CH2Cl2–MeOH, 99:1).
1H NMR (300 MHz, CDCl3): d = 7.50–7.20 (m, 10 H, HAr), 5.85 (m,
1 H, H4), 5.59 (m, 1 H, H3), 4.74 (dd, J = 10.5, 1.5 Hz, 1 H, CHOH),
3.86 (s, 2 H, CH2Ar), 3.38 (br d, J = 11.4 Hz, 1 H, H2), 3.17 (m, 1
H, H6), 2.76 (dd, J = 14.1, 6.0 Hz, 1 H, H6), 2.32 (m, 1 H, H5), 1.84–
1.78 (m, 2 H, H5, CH2CHOH), 1.65 (dt, J = 14.7, 2.4 Hz, 1 H,
CH2CHOH).
1H NMR (300 MHz, CDCl3): 7.40–7.22 (m, 7 H, HAr), 7.04 (t,
J = 9.0 Hz, 2 H, HAr), 5.83 (m, 1 H, H4), 5.58 (m, 1 H, H3), 4.73 (d,
J = 9 Hz, 1 H, CHOH), 3.83 (s, 2 H, CH2Ar), 3.37 (br d, J = 10.35
Hz, 1 H, H2), 3.21 (ddd J = 14.04, 11.85, 4.80 Hz, 1 H, H6), 2.74
(dd, J = 14.04, 5.67 Hz, 1 H, H6), 2.30 (m, 1 H, H5), 1.90–1.75 (m,
2 H, H5, CH2CHOH), 1.67 (dt, J = 14.67, 2.52 Hz, 1 H,
CH2CHOH).
1
13C NMR (75 MHz, CDCl3): d = 162.24 (d, JCF = 24.5 Hz, CF),
144.88 (CAr), 133.6 (CAr), 130.90 (d, 1JCF = 8.25 Hz, 2 CAr), 128.21
(2 CAr), 127.76 (CAr), 127.01 (CAr), 125.56 (2 CAr), 125.24 (C4),
2
115.45 (d, JCF = 21 Hz, 2 CAr), 75.27 (CHOH), 59.04 (C2), 56.36
(CH2Ar), 41.35 (CH2CHOH), 40.51 (C6), 18.59 (C5).
13C NMR (75 MHz, CDCl3): d = 144.98 (CAr), 137.87 (CAr), 129.37
(2 CAr), 128.58 (2 CAr), 128.16 (2 CAr), 127.83 (CAr), 127.50 (CAr),
126.95 (CAr), 125.55 (2 CAr), 125.22 (C4), 75.24 (CHOH), 59.17
(C2), 57.15 (CH2Ar), 41.34 (CH2CHOH), 40.43 (C6), 18.58 (C5).
HRMS (CI): m/z [M + H+] calcd for C20H24NO: 294.1858; found:
294.1858.
HRMS (CI): m/z [M + H+] calcd for C20H23FNO: 312.1764; found:
312.1763.
( )-(1S)-2-[(2R)-1-(4-Methoxybenzyl)-1,2,5,6-tetrahydropyri-
din-2-yl]-1-phenylethanol [( )-9f]
Following the general procedure and starting from 6f (1.7 g, 4.8
mmol), column chromatography (CH2Cl2–Et2O, 95:5 to 90:10) af-
forded ( )-9f (0.74 g, 50%) as a brown oil; Rf = 0.34 (CH2Cl2–
MeOH, 99:1).
1H NMR (300 MHz, CDCl3): d = 7.34–7.21 (m, 7 H, HAr), 6.89 (d,
J = 8.58 Hz, 2 H, HAr), 5.83 (m, 1 H, H4), 5.58 (m, 1 H, H3), 4.71 (br
d, J = 10.17 Hz, 1 H, CHOH), 3.82 (s, 5 H, CH2Ar, OMe), 3.39 (br
d, J = 9 Hz, 1 H, H2), 3.17 (ddd J = 13.7, 11.82, 4.92 Hz, 1 H, H6),
2.77 (dd, J = 13.7, 5.04 Hz, 1 H, H6), 2.32 (m, 1 H, H5), 1.90–1.68
(m, 3 H, H5, CH2CHOH).
13C NMR (75 MHz, CDCl3): d = 159.01 (CAr), 145.05 (CAr), 130.55
(2 CAr), 129.91 (CAr), 128.17 (2 CAr), 127.86 (CAr), 126.93 (CAr),
125.58 (2 CAr), 125.24 (C4), 113.94 (2 CAr), 75.24 (CHOH), 58.84
(C2), 56.43 (CH2Ar), 55.27 (OCH3), 41.34 (CH2CHOH), 40.44
(C6), 18.61 (C5).
( )-(1S)-2-[(2R)-1-(4-Bromobenzyl)-1,2,5,6-tetrahydropyridin-
2-yl]-1-phenylethanol [( )-9c]
Following the general procedure and starting from 6c (1.25 g, 2.7
mmol), column chromatography (CH2Cl2–Et2O, 95:5 to 80:20) af-
forded pure ( )-9c (0.57 g, 56%) as a colorless oil which rapidly
turned brown; Rf = 0.75 (CH2Cl2–MeOH, 99:1).
1H NMR (300 MHz, CDCl3): d = 7.40–7.00 (m, 9 H, HAr), 5.83 (m,
1 H, H4), 5.58 (m, 1 H, H3), 4.72 (dd, J = 10.5, 2.1 Hz, 1 H, CHOH),
3.81 (s, 2 H, CH2Ar), 3.38 (br d, J = 12 Hz, 1 H, H2), 3.17 (m, 1 H,
H6), 2.77 (dd, J = 14.1, 5.7 Hz, 1 H, H6), 2.33 (m, 1 H, H5), 1.86–
1.75 (m, 2 H, H5, CH2CHOH), 1.65 (dt, J = 14.7, 2.7 Hz, 1 H,
CH2CHOH).
13C NMR (75 MHz, CDCl3): d = 144.84 (CAr), 136.92 (CAr), 131.74
(2 CAr), 131.05 (2 CAr), 128.22 (2 CAr), 127.72 (CAr), 127.03 (CAr),
125.55 (2 CAr), 125.24 (C4), 121.45 (CAr), 75.24 (CHOH), 59.16
(C2), 56.52 (CH2Ar), 41.34 (CH2CHOH), 40.60 (C6), 18.60 (C5).
HRMS (CI): m/z [M + H+] calcd for C21H26NO2: 324.1964; found:
324.1964.
( )-Sedamine [( )-1]
HRMS (CI): m/z [M + H+] calcd for C20H23BrNO: 372.0963; found:
A catalytic amount of Raney Ni (50% slurry soln in water washed
with MeOH under argon) was added to ( )-9a (0.2 g, 0.92 mmol) in
MeOH (5 mL). The resulting mixture was stirred under an atmo-
sphere of H2 (balloon) for 22 h. Then, the mixture was filtered and
the solvent evaporated in vacuo to afford quantitatively ( )-
sedamine [( )-1] (0.2 g) as a beige solid; mp 87–90 °C (Lit.11a 90
°C).
1H NMR (300 MHz, CDCl3): d = 7.40–7.15 (m, 5 H, HAr), 4.79 (dd,
J = 10.5, 2.7 Hz, 1 H, CHOH), 3.03–2.95 (m, 1 H, H6), 2.89–2.69
(m, 1 H, H2), 2.50–2.35 (m, 1 H, H6), 2.40 (s, 3 H, NCH3), 2.12–2.00
(m, 1 H, CH2CHOH), 1.82–1.20 (m, 7 H, H3, H4, H5, CH2CHOH).
372.0962.
( )-(1S)-2-[(2R)-1-(4-Nitrobenzyl)-1,2,5,6-tetrahydropyridin-2-
yl]-1-phenylethanol [( )-9d]
Following the general procedure and starting from 6d (1.6 g, 3.8
mmol), column chromatography (PE–Et2O, 50:50) afforded ( )-9d
(0.82 g, 63%) as a brown oil; Rf = 0.90 (CH2Cl2–MeOH, 99:1).
1H NMR (300 MHz, CDCl3): d = 8.22 (d, J = 6.0 Hz, 2 H, HAr), 7.60
(d, J = 6.0 Hz, 2 H, HAr) 7.36–7.22 (m, 5 H, HAr), 5.88 (m, 1 H, H4),
5.62 (m, 1 H, H3), 4.73 (dd, J = 12.00, 3.00 Hz, 1 H, CHOH), 3.95
(s, 2 H, CH2Ar), 3.35 (br d, J = 9.0 Hz, 1 H, H2), 3.21 (ddd, J = 4.92,
11.82, 14.1 Hz, 1 H, H6), 2.74 (dd, J = 14.13, 5.76 Hz, 1 H, H6), 2.31
(m, 1 H, H5), 1.86–1.75 (m, 2 H, H5, CH2CHOH), 1.70 (dt,
J = 14.76, 2.73 Hz, 1 H, CH2CHOH).
13C NMR (75 MHz, CDCl3): d = 145.26 (CAr), 127.99 (2 CAr),
126.75 (CAr), 125.34 (2 CAr), 73.21 (CHOH), 60.64 (C2), 52.21 (C6),
40.13 (NCH3), 10.06 (CH2CHOH), 26.31, 22.28, 21.21 (C3, C4, C5).
Synthesis 2010, No. 14, 2456–2462 © Thieme Stuttgart · New York