3188 J . Org. Chem., Vol. 65, No. 10, 2000
Yu et al.
dried (K2CO3). The solvent was removed under reduced pres-
sure, and the residue was chromatographed (silica gel, EtOAc/
hexane, 20/80) to provide the hemiacetal 32 (323 mg, 78%).
(10H, m), 7.57(1H, d, J ) 6.4 Hz); 13C NMR (75.5 MHz, CDCl3)
δ 8.9, 22.9, 25.2, 28.6, 29.0, 33.1, 51.6, 53.5, 55.5, 57.3, 60.3,
60.5, 101.7, 107.3, 108.8, 118.1, 118.9, 120.7, 126.6, 126.9,
127.3, 128.3, 128.4, 128.5, 133.3, 137.8, 139.6; CIMS (m/e,
relative intensity) 572 (M + 1, 100).
32 [two (OH) diastereomers]: FTIR (KBr) 1460, 3505 cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.77 (3H, t, J ) 7.6 Hz), 1.02-
1.27 (2H, m), 1.49 (1H, m), 1.63 (1H, m), 1.98 (1H, m), 2.45
(2H, t, 16.3 Hz), 3.07 (2H, t, 6.4 Hz), 3.27 (2H, d, J ) 16.4
Hz), 3.43 (1H, m), 3.56 (3H, s), 3.74 (1H, m), 3.97 (1H, s), 4.70
(1H, t, J ) 11.3 Hz), 5.05-5.15 (1H, m), 7.05-7.35 (8H, m),
7.53 (1H, d, J ) 6.8 Hz); 13C NMR (75.5 MHz, CDCl3) δ 12.7,
13.1, 13.8, 18.1, 22.6, 23.0, 23.1, 25.2, 28.9, 29.1, 30.8, 31.1,
32.1, 37.6, 38.2, 43.2, 44.3, 51.2, 51.6, 52.6, 53.2, 57.6, 59.8,
67.0, 94.8, 95.0, 107.0, 107.1, 108.8, 118.0, 118.1, 118.7, 118.8,
120.7, 120.8, 125.5, 126.5, 126.9, 128.2, 128.5, 132.8, 133.1,
137.0, 138.8, 139.7; CIMS (m/e, relative intensity) 417 (M +
1, 100), 399 (40).
On e-P ot Oxyselen a tion of En ol Eth er (12) w ith N-
P h en ylselen op h th a lim id e (34) F ollow ed by Selen oxid e
Elim in a tion w ith Na IO4 To P r ovid e Olefin s (11a ) a n d
(11b). To a solution of enol ether 12 (240 mg, 0.60 mmol) in
CH2Cl2 (10 mL) were added N-phenylselenophthalimide 3452
(244 mg, 0.81 mmol), p-toluenesulfonic acid (130 mg, 0.68
mmol), and CH3OH (1 mL). The reaction mixture was stirred
at 0 °C for 20 h. It was then diluted with CH2Cl2 and brought
to an alkaline pH with an aqueous solution of NH4OH (10%)
at 0 °C. The aqueous layer was separated and extracted with
CH2Cl2. The combined organic layers were dried (K2CO3) and
concentrated in vacuo. The residue was dissolved in THF (11
mL) at 0 °C, and a solution of NaIO4 (82 mg, 0.384 mmol) in
H2O (2.4 mL) was added. The reaction mixture was allowed
to stir at room temperature for 5 h. The precipitate that formed
was removed by filtration, and the reaction mixture was
concentrated under reduced pressure, after which it was
brought to alkaline pH with an aqueous solution of NH4OH
(10%) at 0 °C. The aqueous layer was extracted with CHCl3.
The organic extracts were washed with brine, dried (K2CO3),
and then concentrated under reduced pressure. The residue
was purified by flash chromatography (silica gel, EtOAc-
hexane, 2:8) to provide olefin 11a (185 mg, 72%) as an
amorphous powder accompanied by 11b (46 mg, 18%).
11a : 1H NMR (300 MHz, CDCl3) δ 1.32 (1H, dq, J ) 12.9,
2.5 Hz), 1.50 (3H, d, J ) 13.0 Hz), 1.60 (1H, dt, J ) 12.8, 4.8
Hz), 1.90 (1H, dt, J ) 11.8, 4.1 Hz), 2.37 (1H, d, J ) 16.6 Hz),
2.72 (1H, dt, J ) 12.9, 4.2 Hz), 2.96 (1H, d, J ) 7.1 Hz), 3.18
(1H, dd, J ) 16.6, 7.1 Hz), 3.39 (1H, dd, J ) 10.2, 4.5 Hz),
3.41 (3H, s), 3.48 (3H, s), 3.52 (2H, s), 3.88 (1H, t, 3.1 Hz),
4.48 (1H, t, 11.5 Hz), 5.09 (1H, q, J ) 7.0 Hz), 5.17 (1H, s),
7.06 (1H, t, J ) 7.3 Hz), 7.15-7.25 (7H, m), 7.46 (1H, d, J )
7.5 Hz); 13C NMR (75.5 MHz, CDCl3) δ 12.7, 22.7, 29.0, 33.2,
34.4, 43.7, 51.6, 52.6, 55.0, 57.7, 60.1, 96.5, 107.0, 108.9, 118.1,
118.8, 120.8, 123.6, 127.1, 127.4, 128.7, 128.9, 134.1, 136.5,
137.0, 139.6; EIMS (m/e, relative intensity) 428 (M, 90), 397
(20), 305 (15), 273 (85), 181 (40),170 (95).
Anal. Calcd for C27H32N2O2: C, 77.89; H, 7.69; N, 6.73.
Found: C, 77.74; H, 7.91; N, 6.65.
Deh yd r a tion of Hem ia ceta l (32) w ith p-TSA To P r o-
vid e En ol Eth er (12). A solution of hemiacetal 32 (300 mg,
0.71 mmol) and p-toluenesulfonic acid (185 mg, 0.97 mmol) in
dry benzene (10 mL) was heated to reflux with a DST under
N2 for 3 h. The reaction mixture was then allowed to cool and
was diluted with EtOAc and brought to alkaline pH with an
aqueous solution of NH4OH (10%) at 0 °C. The aqueous layer
was extracted with EtOAc, and the combined organic layers
were washed with brine and dried (Na2SO4). The solvent was
removed under reduced pressure and the residue was purified
by flash column chromatography (silica gel, EtOAc/hexane, 20/
80) to afford enol ether 12 (270 mg, 95%).
12: mp 166-167 °C; IR (KBr) 1470, 1670 cm-1 1H NMR
;
(300 MHz, CDCl3) δ 0.73 (3H, t, J ) 7.6 Hz), 1.63-1.72 (2H,
m), 1.77 (1H, d, J ) 9.2 Hz), 1.92-2.11 (2H, m), 2.45 (1H, d,
16.5 Hz), 3.07 (1H, d, 7.0 Hz), 3.21 (1H, dt, J ) 16.5, 7.0 Hz),
3.48 (3H, s), 3.51 (1H, d, J ) 3.0 Hz), 3.91-3.97 (2H, m), 4.43
(1H, t, J ) 10.8 Hz), 6.07 (1H, s), 7.07 (1H, t, J ) 7.7 Hz), 7.13
(1H, t, J ) 7.7 Hz), 7.28-7.35 (6H, m), 7.47 (1H, d, J ) 7.7
Hz); 13C NMR (75.5 MHz, CDCl3) δ 13.4, 23.7, 24.0, 27.9, 29.5,
33.6, 40.8, 51.6, 53.8, 57.9, 66.6, 107.2, 109.3, 118.0, 118.5,
119.3, 121.3, 127.1, 127.4, 128.7, 128.9, 134.4, 137.5, 138.3,
140.4; EIMS (m/e, relative intensity) 398 (M, 80), 307 (20), 273
(60), 170 (100), 146 (90).
Anal. Calcd for C27H30N2O: C, 81.37; H, 7.54; N, 7.04.
Found: C, 81.00; H, 7.69; N, 7.03.
Anal. Calcd for C28H32N2O2: C, 78.50; H, 7.48; N, 6.54.
Found: C, 78.26; H, 7.88; N, 6.58.
Oxyselen a tion of En ol Eth er (12) w ith N-P h en ylsele-
n op h th a lim id e (34) To P r ovid e Selen oa ceta ls (35a ) a n d
(35b). To a solution of enol ether 12 (120 mg, 0.30 mmol) in
CH2Cl2 (5 mL) were added N-phenylselenophthalimide 3452
(122 mg, 0.41 mmol), p-toluenesulfonic acid (65 mg, 0.34
mmol), and CH3OH (0.5 mL). The reaction mixture was stirred
at 0 °C for 20 h. It was then diluted with CH2Cl2 (10 mL) and
brought to an alkaline pH with an aqueous solution of NH4-
OH (10%) at 0 °C. The aqueous layer was separated and
extracted with CH2Cl2. The combined organic layers were dried
(K2CO3) and concentrated under vacuum. The residue was
purified by flash chromatography (silica gel, EtOAc-hexane,
2:8) to provide selenoacetal 35a (135 mg, 82%) as an amor-
phous powder accompanied by 35b (16 mg, 9%).
11b: 1H NMR (300 MHz, CDCl3) δ 1.21 (3H, d, J ) 13.0
Hz), 1.40-1.60 (2H, m), 1.93 (1H, dt, J ) 11.8, 4.1 Hz), 2.45
(1H, d, J ) 16.6 Hz), 2.70-2.80 (1H, m), 2.96 (1H, d, J ) 7.1
Hz), 3.18 (1H, dd, J ) 16.6, 7.1 Hz), 3.39 (1H, dd, J ) 10.2,
4.5 Hz), 3.41 (3H, s), 3.48 (3H, s), 3.52 (2H, s), 3.88 (1H, t, 3.1
Hz), 4.48 (1H, t, 11.5 Hz), 4.71 (1H, s), 5.40 (1H, q, J ) 7.0
Hz), 7.06 (1H, t, J ) 7.3 Hz), 7.15-7.25 (7H, m), 7.46 (1H, d,
J ) 7.5 Hz); 13C NMR (75.5 MHz, CDCl3) δ 11.9, 22.7, 26.9,
28.9, 30.9, 42.8, 51.6, 52.6, 54.7, 57.7, 60.1, 103.5, 107.0, 108.9,
118.1, 118.8, 120.8, 123.6, 126.7, 127.0, 128.3, 128.6, 133.8,
136.5, 137.0, 139.6; EIMS (m/e, relative intensity) 428 (M, 100),
297 (30), 273 (90), 170 (100), 146 (70).
Anal. Calcd for C28H32N2O2: C, 78.50; H, 7.48; N, 6.54.
Found: C, 78.16; H, 7.87; N, 6.47.
35a : 1H NMR (300 MHz, CDCl3) δ 0.66 (3H, t, J ) 7.5 Hz),
1.41-1.49 (1H, m), 1.74 (1H, d, J ) 11.9 Hz), 1.86-1.91 (1H,
m), 2.05-2.13 (1H, m), 2.39 (1H, d, J ) 16.7 Hz), 2.32-2.53
(1H, m), 3.00 (1H, d, J ) 7.1 Hz), 3.24 (1H, dd, J ) 16.7, 7.2
Hz), 3.45 (2H, s), 3.50 (3H, s), 3.82 (1H, dd, J ) 11.7, 4.6 Hz),
4.00 (1H, t, 2.9 Hz), 4.46 (1H, t, 11.9 Hz), 5.25 (1H, s), 6.68-
7.46 (14H, m); 13C NMR (75.5 MHz, CDCl3) δ 10.5, 22.9, 25.0,
29.6, 31.0, 34.9, 42.4, 53.3, 54.6, 58.8, 59.3, 61.4, 68.5, 107.7,
108.9, 110.9, 120.1, 120.8, 122.9, 128.5, 129.1, 130.0, 130.2,
130.3, 130.5, 135.0, 139.1, 139.5, 141.4; CIMS (m/e, relative
intensity) 572 (M + 1, 100).
Acid -Ca ta lyzed Rea r r a n gem en t of 11a F ollow ed by
Ep im er iza tion To P r ovid e Nb-Ben zyl, Nb-21-Secota lp i-
n in e (37). A suspension of olefin 11a (50 mg) in aqueous 5%
H2SO4 (5 mL) was stirred at room temperature for 30 h under
Ar. Then CH2Cl2 (10 mL) was added to the reaction mixture,
and it was brought to alkaline pH with an aqueous solution
of NH4OH (10%) at 0 °C. The aqueous layer was extracted with
CHCl3, and the organic extracts were concentrated under
reduced pressure. The residue was dissolved in a solution of
K2CO3 (20 mg) in EtOH (10 mL), and the reaction mixture,
which resulted, was stirred at room temperature for 24 h. After
removal of the solvent under reduced pressure, CH2Cl2 (10 mL)
was added to the reaction mixture, and it was neutralized with
an aqueous solution of NH4Cl at 0 °C. The aqueous layer was
separated and extracted with CHCl3. The organic extracts were
washed with brine, dried (K2CO3), and then concentrated
35b: 1H NMR (300 MHz, CDCl3) δ 0.86 (3H, m), 1.45-1.5
(2H, m), 1.85-1.86 (1H, m), 2.49 (1H, d, J ) 16.5 Hz), 2.60
(1H, td, J ) 16.6, 3.8 Hz), 2.86-2.96 (1H, m), 3.06 (1H, d, J )
6.5 Hz), 3.36 (2H, s), 3.44 (3H, s), 3.53 (1H, dd, J ) 11.7, 4.3
Hz), 3.62 (1H, s), 3.91 (1H, s), 4.39 (1H, t, 11.6 Hz), 4.46 (1H,
s), 6.72 (2H, t, J ) 7.7 Hz), 7.02 (1H, t, J ) 7.7 Hz), 7.14-7.30