8010 J . Org. Chem., Vol. 63, No. 22, 1998
Boger and Turnbull
1641, 1569 cm-1; FABHRMS (NBA-NaI) m/z 316.1473 (M+,
2.87 (ddd, J ) 7.2, 5.9, 5.9 Hz, 1H), 2.51 (dd, J ) 16.3, 8.6 Hz,
1H), 2.48-2.38 (m, 1H), 2.20-2.13 (m, 1H), 2.10 (dd, J ) 8.1,
3.1 Hz, 1H), 2.03 (dd, J ) 11.8, 7.0 Hz, 1H), 1.76 (dd, J ) 6.0,
3.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 197.2, 149.9, 140.4,
133.8, 128.6, 127.2, 126.4, 125.9, 116.7, 43.5, 38.5, 31.6, 27.3,
C
22H20O2 requires 316.1463).
5-(Ben zyloxy)-1-(h yd r oxym eth yl)-3-m eth oxy-2,3-d ih y-
d r o-1H-ben z[e]in d en e (22). A solution of 21 (0.751 g, 2.38
mmol, 1 equiv) in THF (24 mL) was cooled to 0 °C prior to
dropwise addition of BH3‚SMe2 (0.713 mL, 10 M, 3(9) equiv).
The cooling bath was removed after 5 min, and the mixture
was stirred at 25 °C for 3 h. The excess borane was quenched
with slow addition of H2O (11.0 mL). Oxidative workup was
accomplished by addition of 2.5 M aqueous NaOH (5.0 mL)
followed by 30% aqueous H2O2 (3.20 mL, 12 equiv), and the
resulting heterogeneous solution was stirred vigorously at 25
°C (1 h) and 45 °C (2 h). The cooled reaction mixture was
treated with saturated aqueous NaCl (5.0 mL), and the layers
were separated. The aqueous portion was extracted with
EtOAc (2 × 30 mL), and the combined organic portions were
dried (MgSO4), filtered, and concentrated. Radial chromatog-
raphy (SiO2, 4 mm plate, 30% EtOAc-hexane) provided 22 as
a colorless oil (0.645 g, 81%): mixture of diastereomers (major
diastereomer); 1H NMR (400 MHz, CDCl3) δ 8.15-8.09 (m,
1H), 7.88-7.85 (m, 1H), 7.71 (s, 1H), 7.51-7.35 (m, 7H), 5.17-
5.06 (m, 2H), 4.78 (dd J ) 6.2, 1.8 Hz, 1H), 3.99 (dd, J ) 10.7,
4.7 Hz, 1H), 5.12 (dd, J ) 10.6, 5.3 Hz, 1H), 3.54-3.48 (m,
1H), 3.46 (s, 3H), 2.51 (ddd, J ) 14.0, 8.7, 6.3 Hz, 1H), 2.25 (t,
J ) 6.4 Hz, 1H), 2.03 (ddd, J ) 14.0, 2.7, 2.7 Hz, 1H); IR (film)
27.2; IR (film) νmax 3056, 2923, 2851, 1662, 1641, 1595 cm-1
;
UV (THF) λmax 241 (ꢀ 35 260) nm; FABHRMS (NBA-NaI) m/z
197.0958 (M + H+, C14H12O requires 197.0966).
(+)-10: [R]25 +12 (c 0.0032, EtOAc) from (+)-23.
D
(-)-10: [R]25 -11 (c 0.0017, EtOAc) from (-)-23.
D
5-Hyd r oxy-1-(h yd r oxym eth yl)-2,3-d ih yd r o-1H-ben z[e]-
in d en e (26). A solution of 22 (0.006 g, 0.018 mmol, 1 equiv)
in EtOAc (0.4 mL) was treated with 10% Pd-C (0.002 g, 0.002
mmol, 0.1 equiv), and the reaction vessel was equipped with
an H2-filled balloon. After 1 h of stirring at 25 °C, the crude
mixture was filtered through a plug of Celite. Radial chro-
matography (SiO2, 1 mm plate, 20% EtOAc-hexane) furnished
26 as a pale yellow oil (0.0028 g, 74%): 1H NMR (400 MHz,
acetone-d6) δ 10.32 (s, 1H), 8.19-8.17 (m, 1H), 7.69-7.67 (m,
1H), 7.36-7.31 (m, 2H), 7.17 (s, 1H), 6.07-6.03 (m, 1H), 4.12-
4.07 (m, 1H), 3.70-3.61 (m, 1H), 3.61-3.52 (m, 1H), 3.07-
2.88 (m, 2H), 2.30-2.21 (m, 1H), 1.68-1.57 (m, 1H); 1H NMR
(400 MHz, CDCl3) δ 9.35 (s, 1H), 8.25-8.23 (m, 1H), 7.69-
7.66 (m, 1H), 7.41-7.35 (m, 2H), 7.21 (s, 1H), 4.15 (dd, J )
9.1, 3.3 Hz, 1H), 3.83-3.78 (m, 1H), 3.68-3.60 (m, 1H), 3.09-
2.98 (m, 2H), 2.61 (bs, 1H), 2.29 (dddd, J ) 13.0, 8.1, 8.1, 5.0
Hz, 1H), 1.66 (ddd, J ) 16.6, 12.7, 8.2 Hz, 1H); IR (film) νmax
3190, 3038, 2918, 2853, 1634, 1569 cm-1; FABHRMS (NBA-
NaI) m/z 214.0988 (M+, C14H14O2 requires 214.0994).
ν
max 3403, 3055, 2923, 2882, 2820, 1603, 1573 cm-1; FABHRMS
(NBA-NaI) m/z 335.1659 (M + H+, C22H22O3 requires 335.1647).
5-(Be n zyloxy)-1-[((m e t h a n e su lfon yl)oxy)m e t h yl]-3-
m eth oxy-2,3-d ih yd r o-1H-ben z[e]in d en e (23). A solution
of 22 (0.596 g, 1.78 mmol, 1 equiv) in CH2Cl2 (18.0 mL) was
cooled to 0 °C prior to sequential addition of Et3N (1.24 mL,
8.92 mmol, 5 equiv) and CH3SO2Cl (0.276 mL, 3.57 mmol, 2
equiv). The cooling bath was removed after 20 min, and the
mixture was stirred at 25 °C for 1 h. The reaction was
quenched with the addition of saturated aqueous NaHCO3
(0.25 mL), and the layers were separated. The aqueous portion
was extracted with EtOAc (2 × 30 mL), and the combined
organic portions were dried (MgSO4), filtered, and concen-
trated. Radial chromatography (SiO2, 4 mm plate, 50%
EtOAc-hexane) furnished 23 as a white solid (0.709 g, 97%):
mixture of diastereomers (major diastereomer); mp 101-103
°C; 1H NMR (400 MHz, CDCl3) δ 8.15-8.11 (m, 1H), 7.89-
7.86 (m, 1H), 7.70 (s, 1H), 7.52-7.36 (m, 7H), 5.12 (s, 2H),
4.81-4.77 (m, 2H), 4.25 (t, J ) 9.8 Hz, 1H), 3.61-3.51 (m, 1H),
3.44 (s, 3H), 2.91 (s, 3H), 2.46 (m, 1H), 2.25 (ddd, J ) 14.0,
3.2, 3.2 Hz, 1H); IR (film) νmax 3058, 3025, 2926, 2816, 1600,
1573 cm-1; FABHRMS (NBA-CsI) m/z 545.0414 (M + Cs+,
Acid -Ca ta lyzed Ad d ition of H2O to 10: 2,6-Dih yd r oxy-
1,2,3,4-tetr a h yd r op h en a n th r en e (25). A solution of 10
(0.0029 g, 0.015 mmol, 1 equiv) in THF (0.3 mL) was treated
with H2O (0.10 mL) followed by CF3SO3H (0.053 mL, 0.1 M in
H2O, 0.36 equiv) at 25 °C, and the mixture was stirred for 2
h. The reaction mixture was treated with NaHCO3 (0.01 g)
followed by H2O (0.5 mL). The aqueous portion was extracted
with EtOAc (2 × 1 mL), and the combined organic portions
were dried (MgSO4), filtered, and concentrated to a colorless
oil. 1H NMR analysis of the crude mixture and comparison
with 26 indicated the presence of the ring expansion solvolysis
product in great excess (>15:1). Radial chromatography (SiO2,
1 mm plate, 50-75% EtOAc-hexane) provided 25 as a
colorless oil (0.0028 g, 88%): 1H NMR (400 MHz, acetone-d6)
δ 8.17-8.14 (m, 1H), 7.93 (s, 1H), 7.70-7.67 (m, 1H), 7.37-
7.30 (m, 2H), 7.17 (s, 1H), 4.17-4.10 (m, 1H), 3.95 (d, J ) 4.2
Hz, 1H), 3.25 (dd, J ) 16.7, 5.2 Hz, 1H), 3.10 (ddd, J ) 16.6,
5.8, 5.8 Hz, 1H), 2.96-2.87 (m, 1H), 2.72 (dd, J ) 16.7, 7.8
Hz, 1H), 2.05-2.03 (m obscured by solvent, 1H), 1.84-1.71
(m, 1H); 1H NMR (400 MHz, CDCl3) δ 8.03-8.00 (m, 1H),
7.70-7.67 (m, 1H), 7.42-7.37 (m, 2H), 7.23 (s, 1H), 5.16 (bs,
1H), 4.31-4.25 (m, 1H), 3.24-3.12 (m, 2H), 3.03-2.95 (m, 1H),
2.74 (dd, J ) 15.9, 7.8 Hz, 1H), 2.14-2.09 (m, 1H), 1.92-1.85
C
23H24O5S requires 545.0399).
Anal. Calcd for C23H24O5S: C, 66.97; H, 5.87; S, 7.76.
Found: C, 66.80; H, 5.60; S, 7.88.
A solution of 23 (0.100 g) in 50% i-PrOH/hexane was
resolved on a semipreparative Diacel Chiracel OD column (10
µm, 2 × 25 cm) using 20% i-PrOH/hexane as eluent (7 mL/
min). The effluent was monitored at 254 nm, and the
enantiomers of the major diastereomer were eluted with
retention times of 23.9 and 30.1 min, respectively (R ) 1.26).
The fractions were collected and concentrated to afford (+)-
23 (tR ) 23.9 min/0.031 g) and (-)-23 (tR ) 30.1 min/0.032 g)
with an 84% recovery based on the starting diastereomeric
ratio (>99.9% ee).
(m, 1H); IR (film) νmax 3333, 3046, 2923, 1651, 1595, 1569 cm-1
;
UV (THF) λmax 238 (ꢀ 26 680), 216 (ꢀ 12 920) nm; FABHRMS
(NBA-NaI) m/z 214.0986 (M+, C14H14O2 requires 214.0994).
A solution of (-)-10 (0.0020 g, 0.010 mmol, 1 equiv) in THF
(0.3 mL) was treated with H2O (0.1 mL) followed by CF3SO3H
(0.37 mL, 0.1 M in H2O, 0.36 equiv) at 25 °C, and the mixture
was stirred for 2 h. Workup as described for racemic 10 and
radial chromatography (SiO2, 1 mm plate, 50-75% EtOAc-
hexane) provided 25 as a colorless oil (0.0015 g, 69%). This
material was identical with racemic 25 except the solvolysis
provided a single enantiomer (Figure 6) established by chiral
phase HPLC separation on a Chiralcel AD column (10 µm, 0.46
× 25 cm, 15% i-PrOH/hexane, 2 mL/min).
(+)-23: [R]25 +10 (c 0.016, THF).
D
(-)-23: [R]25 -11 (c 0.016, THF).
D
2,3,9,9a -Tetr a h yd r o-1H-cyclop r op a [c]ben z[e]in d en -4-
on e (CBIn , 10). A solution of 23 (0.256 g, 0.62 mmol, 1 equiv)
in EtOAc (13 mL) was treated with 10% Pd-C (0.126 g, 0.18
mmol, 0.2 equiv) and the reaction vessel was equipped with
an H2-filled balloon. After 2 h of stirring at 25 °C, the crude
mixture was filtered through a plug of Celite. Concentration
gave 24 as a pale yellow oil that was dissolved in CH3CN (15
mL), treated with DBU (0.143 mL, 0.68 mmol, 1.1 equiv), and
stirred at 25 °C for 5 min. Radial chromatography of the crude
reaction solution (SiO2, 1 mm plate, 20% EtOAc-hexane)
furnished 10 as a bright yellow solid (0.079 g, 65%): mp 53-
(+)-25: [R]25 +26 (c 0.00075, EtOAc).
D
A solution of (+)-10 (0.0021 g, 0.011 mmol, 1 equiv) in THF
(0.3 mL) was treated with H2O (0.1 mL) followed by CF3SO3H
(0.039 mL, 0.1 M in H2O, 0.36 equiv at 25 °C, and the mixture
was stirred for 2 h. Workup as described for racemic 25, and
radial chromatography (SiO2, 1 mm plate, 50-75% EtOAc-
hexane) provided 25 as a colorless oil (0.0018 g, 79%). This
material was identical with racemic 25 except the solvolysis
of (+)-10 provided a single enantiomer established by chiral
1
54 °C; H NMR (400 MHz, CDCl3) δ 8.07-8.05 (m, 1H), 7.55
(ddd, J ) 8.9, 7.5, 1.4 Hz, 1H), 7.33-7.26 (m, 2H), 6.54 (s, 1H),