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A. Friberg et al. / Tetrahedron: Asymmetry 18 (2007) 885–891
˚
0 ꢁC under an argon atmosphere. The resulting mixture
was stirred at 0 ꢁC for 25 min and then MeI (174 lL,
2.79 mmol) was added. The mixture was stirred at 0 ꢁC
for another 5 min and then at rt overnight after which
water (10 mL) was added. The layers were separated and
the aqueous phase extracted with EtOAc (3 · 20 mL).
The collected extracts were washed with satd NaHCO3
(3 · 60 mL), dried over Na2SO4 and the solvent was re-
moved at reduced pressure. The residue was purified by
column chromatography (SiO2, pentane–acetone 95:5,
(+)-7 (200 mg, 0.5 mmol) and 4 A molecular sieves in tolu-
ene (2 mL). The resulting mixture was stirred at reflux tem-
perature for 22 h and then cooled to ambient temperature.
The mixture was filtered, the molecular sieves were washed
with EtOAc (3 · 10 mL) and the solvent removed at re-
duced pressure to give the benzyl imine as a pale yellow
oil, which was used directly in the next step; TLC Rf
0.57, blue spot (heptane–EtOAc 1:1). NaBH4 (80 mg,
2.1 mmol) was added to a mixture of the benzyl imine in
MeOH (20 mL). The resulting mixture was stirred at reflux
temperature for 2.5 h and then cooled to rt after which
water (20 mL) was added and worked up as follows: extrac-
tion with EtOAc (3 · 15 mL) followed by drying (Na2SO4)
and removal of the solvent at reduced pressure. The residue
was purified by column chromatography (SiO2, pentane–
ether 85:15) to give (+)-10 (127 mg, 52%) of >99% ee as
TLC Rf 0.29) to give (+)-8 (153 mg, 98%) of >99% ee as
20
a white solid: mp 225–226 ꢁC; ½aꢁD ¼ þ126 (c 1.03, CHCl3);
1
IR (KBr) 1683 cmꢀ1; H NMR (400 MHz, CDCl3) d 2.32
(1H, dt, J = 13.5, 2.8 Hz), 2.40 (1H, ddd, J = 13.6, 3.9,
2.7 Hz), 2.65 (3H, s), 3.88 (1H, m) 4.28 (1H, m), 6.67
(1H, dd, J = 7.4, 0.8 Hz), 7.23 (1H, t, J = 7.8 Hz), 7.29–
7.40 (3H, m), 7.43 (1H, td, J = 7.8, 1.0 Hz), 7.52–7.62
(2H, m), 7.66 (1H, td, J = 7.5, 1.4 Hz), 7.76 (1H, m), 7.81
(1H, d, J = 8.1 Hz), 7.95 (1H, d, J = 7.9 Hz), 8.00 (1H, d,
J = 7.6 Hz), 8.07 (1H, dd, J = 7.8, 1.2 Hz), 9.53 (1H, d,
J = 8.8 Hz); 13C NMR (400 MHz, CDCl3) d 31.2, 44.1,
48.6, 56.1, 87.8, 124.3, 125.6, 126.2, 127.9, 128.0, 128.2,
128.4, 128.8, 129.4, 129.6, 129.7, 129.7, 130.9, 131.5,
131.7, 132.0, 133.8, 135.4, 135.5, 136.8, 143.2, 144.5,
197.2; HRMS (FAB+, direct inlet) [M]: calcd for
C28H22O2: 390.1620. Found: 390.1604 (Found: C, 86.09;
H, 5.62. C28H22O2 requires C, 86.13; H, 5.68).
a white solid: TLC Rf 0.52, blue spot (heptane–EtOAc
20
1:1,); mp 94–96 ꢁC; ½aꢁD ¼ þ66 (c 0.79, CHCl3); IR
(KBr) 3545, 3475 cmꢀ1 1H NMR (400 MHz, CDCl3)
;
d 1.68 (1H, br s), 2.04 (1H, dAB, J = 13.1 Hz), 2.36 (1H,
dAB, J = 13.1 Hz), 2.43 (1H, s), 3.60 (1H, br s), 4.07 (1H,
s), 4.19 (1H, d, J = 6.8 Hz), 4.22 (1H, dAB, J = 13.5 Hz),
4.48 (1H, dAB, J = 13.5 Hz), 6.49 (1H, d, J = 6.8 Hz),
7.25–7.42 (7H, m), 7.46 (2H, t, J = 7.2 Hz), 7.55–7.69
(4H, m), 7.74 (1H, t, J = 7.5 Hz), 7.83 (2H, t,
J = 8.7 Hz), 7.96 (1H, d, J = 7.9 Hz), 8.07 (1H, d, J =
6.7 Hz), 9.54 (1H, d, J = 8.4 Hz); 13C NMR (400 MHz,
CDCl3) d 29.1, 33.5, 42.9, 51.3, 61.3, 82.2, 124.2,
125.4, 125.8, 126.5, 127.2, 127.7, 127.8, 127.9, 128.3,
128.6, 128.6, 128.7, 128.8, 129.1, 129.4, 129.9, 130.1,
131.3, 131.6, 135.2, 135.7, 136.1, 140.3, 140.9, 142.4,
143.2; HRMS (FAB+, direct inlet) [M]: calcd for
C34H29NNaO: 490.2147. Found: 490.2127 (Found: C,
87.26; H, 6.18; N, 2.87. C34H29NO requires C, 87.33; H,
6.25; N, 3.00).
4.2.7.
(ꢀ)-(1R,4S,5R,8S)-4,8-Di(1-naphthyl)-8-methoxy-
2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4-ol (–)-9. 1-
NaphthylMgBr (1 M in THF, 1.8 mL, 1.8 mmol) was added
in portions to a solution of (+)-8 (0.292 mmol, 114 mg) in
dry THF (1.5 mL) at rt, under an argon atmosphere. The
resulting mixture was stirred at rt for 5 h whereafter aque-
ous satd NH4Cl (3 mL) was added. The aqueous phase
was extracted with ethyl acetate (3 · 10 mL) and the com-
bined organic phases were washed with aqueous satd NaH-
CO3 and dried over Na2SO4. The solvent was removed at a
reduced pressure and the residue purified by column chro-
matography (Al2O3, heptane–EtOAc 80:20) to give (–)-9
4.2.9. (+)-(1R,4S,5R,8S)-4-Amino-8-(1-naphthyl)-2,3:6,7-
dibenzobicyclo[3.3.1]nona-2,6-diene-8-ol (+)-11. Pd/C 5%
(25 mg) and formic acid (1.25 mL) were added to a solution
of (+)-10 (96 mg, 0.2 mmol) in methanol (5 mL). The
resulting slurry was stirred under a nitrogen atmosphere
at rt for 5 h. The mixture was filtered through a pad of Cel-
ite, which was rinsed with a small amount of formic acid.
The filtrate was neutralized by 2 M NaOH, extracted with
EtOAc, dried over anhydrous Na2SO4 and the solvent re-
moved at a reduced pressure. The residue was purified by
column chromatography (SiO2, heptane–EtOAc–MeOH–
(84 mg, 54%) of >99% ee as a white solid: TLC Rf 0.6
20
(Al2O3, heptane–EtOAc 75:25); mp 245–247 ꢁC; ½aꢁD
¼
ꢀ125 (c 0.27, CHCl3); IR (KBr) 3450 cmꢀ1
;
1H NMR
(400 MHz, CDCl3) d 1.78–1.91 (2H, m), 2.54 (1H, s),
2.81 (3H, s), 3.96–4.02 (1H, m), 4.07–4.12 (1H, m), 6.29
(1H, d, J = 7.3 Hz), 6.92 (1H, dd, J = 7.4, 1.1 Hz), 7.06–
7.15 (2H, m), 7.38 (1H, td, J = 7.7, 1.4 Hz), 7.4–7.44 (2H,
m), 7.48 (1H, td, J = 7.4, 1.3 Hz), 7.50–7.61 (m, 4H),
7.65–7.75 (m, 4H), 7.88 (2H, doublet of multiplets,
J = 8.1 Hz), 8.02 (d, 2H, J = 7.8 Hz), 9.51 (2H, d,
J = 8.7 Hz); 13C NMR (100 MHz, CDCl3) d 28.3, 42.6,
42.8, 56.7, 81.8, 89.7, 124.1, 124.1, 125.4, 125.4, 125.8,
126.0, 127.7, 127.7, 127.8, 127.8, 128.1, 128.3, 129.1,
129.2, 129.5, 129.5, 129.6, 129.8, 129.8, 131.3, 131.6,
131.9, 132.2, 132.5, 135.2, 135.3, 137.6, 138.2, 138.9,
142.7, 142.7, 143.1; HRMS (FAB+, direct inlet) [M]: calcd
for C38H30NaO2: 541.2143. Found: 541.2146 (Found: C,
88.01; H, 5.53. C38H30O2 requires C, 88.00; H, 5.83).
NH4OH 57:38:4:1, TLC Rf 0.13) to give (+)-11 (69 mg,
20
90%) in >99% ee as a white solid: mp 149–153 ꢁC; ½aꢁD
¼
þ8:9 (c 0.9, CHCl3); IR (KBr) 3554, 3365, 3295 cmꢀ1
;
1H NMR (400 MHz, CDCl3) d 1.90–2.17 (2H, br s), 2.07
(1H, s), 2.07 (1H, dddAB, J = 13.6, 4.3, 2.1 Hz), 2.27 (1H,
dddAB, J = 13.6, 4.3, 2.1 Hz), 3.20–3.26 (1H, m), 4.03
(1H, d, J = 2.2 Hz), 4.32 (1H, d, J = 5.0 Hz), 6.38 (1H, d,
J = 7.3 Hz), 7.19 (1H, t, J = 7.9 Hz), 7.28–7.40 (4H, m),
7.40–7.46 (1H, m), 7.51–7.59 (2H, m), 7.65–7.72 (2H, m),
7.78 (1H, d, J = 8.1 Hz), 7.83 (1H, dd, J = 7.5, 1.3 Hz),
7.92 (1H, d, J = 8.2 Hz), 9.47 (1H, d, J = 8.8 Hz);
13C NMR (400 MHz, CDCl3) 29.3, 40.3, 43.1, 55.6,
82.2, 124.2, 125.5, 125.8, 126.7, 127.4, 127.7, 127.8, 128.1,
128.2, 129.2, 129.5, 129.9, 130.1, 130.2, 131.3, 132.1,
135.2, 135.4, 135.6, 140.7, 142.5, 143.1; HRMS (FAB+,
4.2.8. (+)-(1R,4S,5R,8S)-4-Benzylamino-8-(1-naphthyl)-2,3:
6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-8-ol (+)-10. Benz-
ylamine (0.46 mL, 4.2 mmol) was added to a mixture of