Sasaki et al.
14.2, 14.1, -5.0, -5.2; HRMS (FAB) m/z calcd for C26H44NO8Si
(MH+) 526.2836, found 526.2844.
MHz, CDCl3) δ 160.1, 159.8, 158.3, 136.5, 130.8, 117.1, 111.1,
104.5, 98.3, 77.9, 57.9, 55.4, 41.1, 25.6, 18.0 16.9, -4.4, -4.6;
HRMS (ESI-TOF) m/z calcd for C21H33INO4Si (MH+) 518.1224,
found 518.1225.
(5S,6S)-5-(tert-Butyldimethylsilanyloxy)-1-(2,4-dimethoxyben-
zyl)-6-methyl-4-trifluoromethanesulfonyloxy-5,6-dihydro-1H-
pyridin-2-one (18) from 16. To a solution of 16 (560 mg, 1.07
mmol) in EtOH (2 mL) was added 6 mL (1.28 mmol) of freshly
prepared NaOEt in EtOH (0.213 M) at 0 °C under argon, and the
mixture was stirred for 30 min. After additional stirring at room
temperature for 2 h, the reaction mixture was quenched with 1 N
HCl at 0 °C. The mixture was washed with brine, dried over
MgSO4, and concentrated in vacuo to give an oil material, which
was used for following reactions without further purification. A
mixture of the oil in 150 µL of H2O and 30 mL of CH3CN was
refluxed for 2 h and concentrated under reduced pressure to give
solid crude materials. To a solution of the crude materials in CH2-
Cl2 (10 mL) were added N-phenylbis(trifluoromethanesulfonimide)
(571 mg, 1.60 mmol) and Et3N (443 µL, 3.20 mmol) at 0 °C, and
the mixture was stirred at room temperature for 12 h. The reaction
mixture was quenched by the addition of 0.1 N HCl and extracted
with Et2O. The mixture was washed with 0.1 N HCl, brine, saturated
NaHCO3, and brine, dried over MgSO4, and concentrated under
reduced pressure to give crude materials. Chromatographic purifica-
tion of the crude materials over silica gel with EtOAc-n-hexane
(1:9) gave the title compound 18 (448 mg, 78.0% yield) as a white
crystal: mp 136-138 °C; [R]24D -103 (c 0.640, CHCl3); 1H NMR
(400 MHz, CDCl3) δ -0.06 (s, 3H), 0.06 (s, 3H), 0.75 (s, 9H),
1.20 (d, J ) 6.8 Hz, 3H), 3.54 (q, J ) 6.8 Hz, 1H), 3.78 (s, 3H),
3.80 (s, 3H), 4.04 (s, 1H), 4.11 (d, J ) 15.0 Hz, 1H), 5.10 (d, J )
15.0 Hz, 1H), 6.13 (s, 1H), 6.40-6.43 (m, 2H), 7.22 (d, J ) 8.8
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 160.2, 160.1, 158.2, 156.4,
130.4, 129.1, 116.5, 115.6, 104.4, 98.2, 70.1, 57.9, 55.2, 41.1, 25.3,
17.7, 16.5, -5.2, -5.3. Anal. Calcd for C22H32F3NO7SSi: C, 48.97;
H, 5.98; N, 2.60. Found: C, 48.67; H, 5.78; N, 2.62.
(5S,6S)1-(2,4-Dimethoxybenzyl)-5-diphenylphosphoryloxy-4-
iodo-6-methyl-5,6-dihydro-1H-pyridin-2-one (4a) from 20. To
a solution of 20 (64.0 mg, 0.115 mmol) in THF (0.5 mL) was added
1 M TBAF in THF (121 µL, 0.121 mmol) at 0 °C. After being
stirred at 0 °C for 1 h, the reaction mixture was quenched with 1
N HCl followed by extraction with EtOAc. The extract was washed
with brine, dried over MgSO4, and concentrated under reduced
pressure to give crude materials, which were used in the following
reaction without further purification. To a solution of the above
materials in pyridine (2 mL) was added diphenylphosphoryl chloride
(47.9 mg, 0.231 mmol) at 0 °C under argon with additional stirring
at room temperature for 12 h. The reaction mixture was quenched
with 1 N HCl and extracted with EtOAc. The extract was washed
with 1 N HCl and brine, dried over MgSO4, and concentrated under
reduced pressure to give oily residues. After chromatographic
purification of the residues over silica gel with EtOAc-n-hexane
(1:9), the title compound 4a (64.8 mg, 88.3% yield) was obtained
1
as a colorless oil: [R]24 -204 (c 0.333, CHCl3); H NMR (400
D
MHz, CDCl3) δ 1.19 (d, J ) 6.8 Hz, 3H), 3.66 (s, 3H), 3.75 (s,
3H), 3.83 (qd, J ) 6.8, 1.6 Hz, 1H), 4.25 (d, J ) 14.8 Hz, 1H),
4.74 (d, J ) 14.8 Hz, 1H), 4.98 (dd, J ) 8.4, 1.6 Hz, 1H), 6.31
(dd, J ) 8.4, 2.4 Hz, 1H), 6.35 (d, J ) 2.4 Hz, 1H), 6.93 (s, 1H),
6.99 (d, J ) 8.4 Hz, 1H), 7.00 (m, 1H), 7.14-7.35 (m, 10H); 13C
NMR (100 MHz, CDCl3) δ 160.3, 159.3, 158.3, 150.2 (d, J ) 7.1
Hz), 150.0 (d, J ) 7.5 Hz), 130.9, 129.7 (d, J ) 5.7 Hz), 125.4 (d,
J ) 7.4 Hz), 125.4, 120.1 (d, J ) 5.0 Hz), 119.9 (d, J ) 4.9 Hz),
116.5, 104.2, 102.7, 100.5, 98.2, 82.3 (d, J ) 5.0 Hz), 60.3, 56.4
(d, J ) 2.5 Hz), 55.3, 55.2, 42.2, 21.1, 17.0, 14.2; HRMS (FAB)
m/z calcd for C27H28INO7P (MH+) 636.0648, found 636.0656.
(5S,6S)1-Benzyl-5-diphenylphosphoryloxy-4-iodo-6-methyl-
5,6-dihydro-1H-pyridin-2-one (4b). By use of synthetic manipula-
tions similar to those described for the preparation of 4a from 14,
4b was obtained from 14 as a colorless oil: [R]20D -75.1 (c 1.13,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.13 (d, J ) 6.8 Hz, 3H),
3.64 (qd, J ) 6.8, 1.2 Hz, 1H), 4.15 (d, J ) 15.2 Hz, 1H), 4.79 (d,
J ) 15.2 Hz, 1H), 4.98 (dd, J ) 8.4, 1.2 Hz, 1H), 6.96 (d, J ) 8.4
Hz, 2H), 6.97 (s, 1H), 7.15-7.35 (m, 13H); 13C NMR (100 MHz,
CDCl3) δ 159.2, 150.1 (d, J ) 7.4 Hz), 149.7 (d, J ) 6.6 Hz),
139.3, 136.0, 129.6, 128.4, 127.9, 127.5, 125.4 (d, J ) 7.4 Hz),
120.0 (d, J ) 5.0 Hz), 119.8 (d, J ) 4.2 Hz), 103.2 (d, J ) 6.6
Hz), 81.9 (d, J ) 5.0 Hz), 56.5 (d, J ) 3.3 Hz), 48.0, 16.9; HRMS
(ESI-TOF) m/z calcd for C25H24INO5P (MH+) 576.0437, found
576.0439.
(5S,6S)-5-(tert-Butyldimethylsilanyloxy)-1-(2,4-dimethoxyben-
zyl)-6-methyl-4-(trimethylstannanyl)-5,6-dihydro-1H-pyridin-2-
one (19) from 18. To a suspension of dried LiCl (141 mg, 3.32
mmol) and PdCl2[P(o-Tol)3]2 (65.3 mg, 0.0830 mmol) in THF (20
mL) was added a solution of 18 (448 mg, 0.830 mmol) in THF (5
mL) at 0 °C under argon, and the mixture was stirred at 50 °C for
20 min. The reaction mixture was quenched and extracted with
saturated NaHCO3 at 0 °C and extracted with Et2O. The extract
was washed with saturated NaHCO3 and brine, dried over MgSO4,
and concentrated under reduced pressure to leave solid residues.
After chromatographic purification of the residues over silica gel
with EtOAc-n-hexane (1:9), the title compound 19 (450 mg, 97.8%
yield) was obtained as a white crystal: mp 143-145 °C; [R]24
D
-95.2 (c 0.039, CHCl3); 1H NMR (400 MHz, CDCl3) δ -0.16 (s,
3H), 0.24 (s, 3H), 0.75 (s, 9H), 1.07 (d, J ) 6.8 Hz, 3H), 3.50 (m,
1H), 3.78 (s, 3H), 3.80 (s, 3H), 4.03 (s, 1H), 4.24 (d, J ) 14.8 Hz,
1H), 4.94 (d, J ) 14.8 Hz, 1H), 6.27 (s, 1H), 6.42 (m, 2H), 7.30
(m, 1H); 13C NMR (75 MHz, CDCl3) δ 160.6, 160.0, 158.3, 154.2,
135.7, 130.8, 117.8, 104.4, 98.1, 70.8, 57.5, 55.3, 55.2, 41.4, 25.6,
17.6, 16.7, -4.2, -4.9, -9.5. Anal. Calcd for C24H41NO4SiSn: C,
52.00; H, 7.45; N, 2.53. Found: C, 51.70; H, 7.44; N, 2.51.
(5S,6S)-5-(tert-Butyldimethylsilanyloxy)-1-(2,4-dimethoxyben-
zyl)-4-iodo-6-methyl-5,6-dihydro-1H-pyridin-2-one (20) from 19.
To a solution of 19 (198 mg, 0.357 mmol) in CH2Cl2 (6 mL) was
added iodine (136 mg, 0.536 mmol) at 0 °C under argon, and the
reaction mixture was stirred at room temperature for 12 h. The
reaction mixture was quenched with a few drops of 28% NH4OH
and extracted with Et2O. The extract was washed with brine, dried
over MgSO4, and concentrated in vacuo to give solid residues.
Chromatography of the residues over silica gel with EtOAc-n-
hexane (1:9) gave the title compound 21 (154 mg, 83.4%) as an
amorphous powder: [R]24D -115 (c 0.686, CHCl3); 1H NMR (400
MHz, CDCl3) δ -0.11 (s, 3H), 0.13 (s, 3H), 0.77 (s, 9H), 1.18 (d,
J ) 6.8 Hz, 3H), 3.44 (m, 1H), 3.78 (s, 3H), 3.79 (s, 3H), 4.07 (s,
1H), 4.11 (d, J ) 15.0 Hz, 1H), 5.01 (d, J ) 15.0 Hz, 1H), 6.41
(m, 2H), 6.75 (s, 1H), 7.24 (d, J ) 8.8 Hz, 1H); 13C NMR (100
(3R,4S)-4-[Benzyl(tert-butoxycarbonyl)amino]pent-1-en-3-
ol (21) from 10. To a solution of 10 (3.48 g, 9.25 mmol) in DMF
(20 mL) were added mercaptacetic acid (1.29 mL, 18.5 mmol) and
LiOH‚H2O (1.55 g, 37.0 mmol) at 0 °C, with additional stirring at
room temperature for 14 h. The reaction mixture was quenched
with saturated NaHCO3 at 0 °C, followed by extraction with EtOAc.
The extract was washed with saturated NaHCO3 and brine, dried
over MgSO4, and concentrated under reduced pressure to give oily
crude. To a solution of the crude in THF (30 mL) were added Boc2O
(2.42 g, 11.1 mmol) and Et3N (1.55 mL, 11.1 mmol) at 0 °C. The
reaction mixture was stirred at room temperature for 14 h, quenched
with saturated citric acid, and extracted with EtOAc. The extract
was washed with saturated citric acid, saturated NaHCO3, and brine,
dried over MgSO4, and concentrated in vacuo to give residues. The
residues were purified by column chromatography over silica gel
with EtOAc-n-hexane (1:9) to give the title compound 21 (1.98
g, 73.6% yield) as a colorless oil: [R]24 4.22 (c 0.946, CHCl3);
D
1H NMR (400 MHz, CDCl3) δ 1.18 (d, J ) 7.2 Hz, 3H), 1.43 (br,
9H), 3.46 (d, J ) 7.2 Hz, 1H), 3.50 (d, J ) 7.2 Hz, 1H), 3.61 (br,
1H), 4.20-4.53 (m, 4H), 5.10 (d, J ) 10.0 Hz, 1H), 5.20 (dt, J )
17.0, 1.6 Hz, 1H), 5.76 (ddd, J ) 17.0, 10.0, 5.8 Hz, 1H), 7.20-
7.35 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 156.6, 139.0, 138.5,
4976 J. Org. Chem., Vol. 71, No. 13, 2006