Jung et al.
SO4, and concentrated in vacuo. The product was separated by flash
column chromatography (Hex/EtOAc ) 1/1, v/v) to produce the
tricyclic enone 29 (3.0 g, 93%) as a colorless oil. For compound
29, 1H NMR (400 MHz, CDCl3): δ 8.03 (d, 2H, J ) 8.8 Hz), 7.69
(m, 1H), 7.56 (m, 2H), 6.27 (s, 1H), 4.11 (ABX, 1H, JAB) 8.6 Hz,
JAX) 5.8 Hz), 3.74∼3.66 (m, 1H), 3.40 (ABX, 1H, JAB) 8.6 Hz,
JAX) 8.6 Hz), 3.19∼3.15 (m, 1H), 2.91 (ABX, 1H, JAB) 18.2 Hz,
JAX) 6.4 Hz), 2.26 (ABX, 1H, JAB) 18.2 Hz, JAX) 0.0 Hz), 1.96
(s, 3H), 1.44 (s, 3H), 1.37 (s, 3H). 13C NMR (100 MHz, CDCl3):
δ 193.9, 162.4, 146.5, 136.2, 135.2, 133.6, 131.4, 129.2,93.4, 80.0,
68.7, 61.3, 41.7, 35.0, 26.2, 23.5, 21.7. IR (thin film, cm-1): 2985,
2928, 1705, 1673, 1146. HRMS (ESI+) for [M + H+] C19H22-
the γ-lactam (2.3 g, 6.3 mmol) in CH2Cl2 (63 mL). The mixture
was stirred for 2 h and concentrated under reduced pressure. The
residue was purified by flash chromatography (Hex/EtOAc ) 1:1,
V/V) to afford the title compound 30 as colorless oil (2.8 g, 95%).
For compound 30, 1H NMR (400 MHz, CDCl3): δ 8.02 (d, 2H, J
) 8.0 Hz), 7.73 (m, 1H), 7.60 (m, 2H), 6.31 (s, 1H), 4.00 (d, 1H,
J ) 10.0 Hz), 3.76 (s, 3H), 3.38 (m, 1H), 2.90 (ABX, 1H, JAB
)
18.2 Hz, JAX) 6.8 Hz), 2.55 (ABX, 1H, JAB) 18.2 Hz, JAX) 0.0
Hz), 1.87 (s, 3H), 1.43 (s, 9H). 13C NMR (100 MHz, CDCl3): δ
192.8, 169.2, 163.8, 147.9, 145.3, 135.8, 135.5, 134.5, 131.4, 129.5,
85.8, 75.0, 60.5, 53.2, 37.5, 33.5, 27.9, 21.7. IR (thin film, cm-1):
2985, 1795, 1754, 1678, 1144. HRMS (ESI+) for [M + Na]+
C22H25NO8SNa: calcd, 486.1193; found, 486.1188; [R]25D ) -28.8
(c 0.32, CHCl3).
NO5S: calcd, 376.1213; found, 376.1211; [R]25 ) +7.7 (c 0.73,
D
CHCl3).
(1S,3rR,7rR)-2-tert-Butyl-1-methyl 4-methyl-3,6-dioxo-3a-
(phenylsulfonyl)-3,3a,7,7a-tetrahydro-1H-isoindole-1,2(6H)-di-
carboxylate (30). To a solution of tricyclic acetonide 29 (3 g, 8
mmol) in MeOH (40 mL, 0.2 M) was added Dowex-50W-8X (9
g) in one portion. The resulting solution was heated under reflux
condition for 10 h. The mixture was filtered and concentrated to
provide the alcohol (2.6 g, 95%) as pale yellowish oil. The product
(1S,3rR,7rR)-2-tert-Butyl-1-methyl 6-(tert-butyldimethylsi-
lyloxy)-4-methylene-3-oxo-3a-(phenylsulfonyl)-3a,4,7,7a-tetrahy-
dro-1H-isoindole-1,2(3H)-dicarboxylate (31 + 32). To a solution
of ester 30 (2.8 g, 6.0 mmol) in CH2Cl2 (240 mL, 0.025 M), was
added freshly distilled (over KOH) Et3N (3.0 g, 4.2 mL, 30 mmol)
and TBSOTf (4.8 g, 4.1 mL, 18 mmol) in CH2Cl2 (5 mL) at 0 °C.
After stirring for 1 h at 20 °C, the mixture was poured into aqueous
saturated NaHCO3 and extracted with CH2Cl2. The combined
organic phases were dried over Na2SO4 and evaporated to give a
residue (3.5 g, 100%), which was purified by chromatography
through a silica gel column with elution by Hex/EtOAc/Et3N (5:
1:1, v/v/v) to give mixture of 31 and 32 (3.5 g, 100%). For
1
was used for the next step without further purification. H NMR
(400 MHz, CD3OD): δ 7.98 (d, 2H, J ) 8.0 Hz), 7.76 (m, 1H),
7.62 (m, 2H), 6.28 (s, 1H), 3.80∼3.20 (m, 4H), 2.35 (d, 2H, J )
2.8), 2.16 (s, 3H). 13C NMR (100 MHz, CD3OD): δ 195.3, 167.7,
147.9,136.1, 135.0, 133.3, 130.7, 129.3, 74.9, 60.4, 57.2, 38.6, 33.0,
21.1. IR (thin film, cm-1): 3340, 2945, 2834, 2071, 1716, 1671,
1448. HRMS (ESI+) for [M + H+] C16H18NO5S: calcd, 336.0900;
1
compound 31,32, H NMR (400 MHz, CDCl3): δ 7.94∼7.40 (m,
5H), 5.54 (s, 1H), 4.87 (s, 1H), 4.53 (s, 1H), 4.03 (d, 1H, J ) 10.4
Hz), 3.77 and 3.70 (s, 3H), 3.50∼3.40 (m, 1H), 2.80 (ABX, 1H,
found, 336.0900; [R]25 ) +4.3 (c 1.59, MeOH).
D
JAB) 18.0 Hz, JAX) 5.8 Hz), 2.23 (ABX, 1H, JAB) 18.0 Hz, JAX
)
Jones’ reagent (1.0 M, 103 mL, 103 mmol) was added to a
solution of the alcohol (2.5 g, 7.5 mmol) in acetone (75 mL, 0.1
M) at room temperature, and the resulting mixture was stirred for
2 h at that temperature. The reaction was quenched with i-PrOH
and concentrated in vacuo. The mixture was dissolved in 50 mL
of CH2Cl2, and 2 mL of brine solution was added. After phase
separation, the aqueous layer was extracted three times with CH2-
Cl2, and the organic layers were combined, dried over Na2SO4, and
concentrated to give the carboxylic acid compound (2.6 g, 99%)
as a white solid, which was used for the next step without further
0.2 Hz), 1.42 and 1.39 (s, 9H), 0.90 and 0.84 (s, 9H), 0.25 and
0.18 and 0.00 (s, 6H). 13C NMR (100 MHz, CD3OD): δ 172.2,
171.4, 171.2, 167.8, 166.7, 152.6, 149.7, 149.6, 137.6, 136.1, 136.0,
135.9, 135.2, 133.0, 132.3, 132.2, 131.7, 130.0, 129.9, 129.5, 127.8,
118.4, 109.2, 107.5, 97.3, 86.3, 86.2, 84.8, 75.9, 73.3, 68.1, 64.9,
63.9, 63.3, 61.8, 58.9, 56.3, 53.6, 53.4, 53.2, 41.2, 37.7, 37.5, 31.9,
30.2, 28.5, 28.1, 28.0, 27.9, 26.7, 26.4, 26.2, 26.0, 25.9, 22.7, 20.0,
18.9, 18.7, -4.1, -4.2, -4.7. IR (thin film, cm-1): 2960, 2214,
2070, 1742, 1242, 1122. HRMS (ESI+) for [M + H+] C28H40NO8-
SSi: calcd, 578.2238; found, 578.2233; [R]25 ) +24.1 (c 0.78,
1
purification: mp 216∼218 °C. H NMR (400 MHz, CD3OD): δ
D
CHCl3).
8.00 (d, 2H, J ) 7.6 Hz), 7.78 (m, 1H), 7.64 (m, 2H), 6.32 (s, 1H),
3.83 (d, 1H, J ) 9.6 Hz), 3.31 (m, 1H), 2.68 (ABX, 1H, JAB) 18.6
Hz, JAX) 0.1 Hz), 2.46 (ABX, 1H, JAB) 18.6 Hz, JAX) 7.3 Hz),
2.12 (s, 3H). 13C NMR (100 MHz, CD3OD): δ 194.67, 170.89,
167.2, 147.2, 135.9, 135.2, 133.6, 130.7, 129.3, 74.3, 56.5, 41.2,
33.5, 20.9. IR (thin film, cm-1): 3352, 2985, 2071, 1718, 1673,
1025. HRMS (ESI-) for [M - H+] C16H14NO6S: calcd, 348.0543;
(1S,3rS,7rS)-2-tert-Butyl-1-methyl 4-methyl-3,6-dioxo-3,-
3a,7,7a-tetrahydro-1H-isoindole-1,2(6H)-dicarboxylate (33). A
10% portion of sodium amalgam (6.9 g, 30 mmol) was added to a
solution of the silyl enol ether compound 31 + 32 (3.5 g, 6.0 mmol)
and anhydrous disodium hydrogen phosphate (2.6 g, 18 mmol) in
a mixture of dry MeOH (12 mL) and THF (108 mL) at -78 °C.
The reaction mixture was warmed to -20 °C and stirred for 3 h.
The reaction solution was quenched with aqueous NH4Cl and
warmed to room temperature. After filtration, the resulting solution
was concentrated in vacuo and diluted with EtOAc (100 mL). The
organic solution was washed with brine, dried over Na2SO4, filtered,
and concentrated. The crude product was purified by chromatog-
raphy through a silica gel column with elution by Hex/EtOAc (1/
1, v/v) to give the product 33 (1.85 g, 95%) as a colorless oil. For
found, 348.0543; [R]25 ) -3.4 (c 0.29, MeOH).
D
To a solution of acid (2.6 g, 7.4 mmol) in a mixture of methanol
(74 mL) and toluene (185 mL), was added TMSCHN2 (5.5 mL,
11.1 mmol, 2 M solution in ether) dropwise at room temperature.
After stirring for 5 min, the reaction was quenched with acetic acid
(2 drops) and the solvent was removed under reduced pressure.
The resulting mixture was diluted with EtOAc (100 mL), washed
with brine, then dried over Na2SO4, and concentrated in vacuo to
give the crude product. The residue was purified by flash chroma-
tography (EtOAc), affording the ester amide product as a colorless
oil (2.3 g, 91%). 1H NMR (400 MHz, CDCl3): δ 7.94 (d, 2H, J )
8.0 Hz), 7.68 (m, 1H), 7.54 (m, 2H), 6.25 (s, 1H), 3.80 (d, 1H, J
) 9.6 Hz), 3.73 (s, 3H), 3.42 (m, 1H), 2.69 (ABX, 1H, JAB) 18.4
Hz, JAX) 0.4 Hz), 2.60 (ABX, 1H, JAB) 18.4 Hz, JAX) 6.8 Hz),
1.98 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ 193.6, 169.5, 167.1,
146.3, 136.0, 135.4, 134.1, 131.0, 129.5, 74.4, 56.5, 53.4, 41.1,
34.2, 21.8. IR (thin film, cm-1): 2985, 1724, 1675, 1149. HRMS
(ESI+) for [M + H+] C17H18NO6S: calcd, 364.0849; found,
1
compound 33, H NMR (400 MHz, CDCl3): δ 5.94 (s, 1H), 4.25
(s, 1H), 3.77 (s, 3H), 3.39 (d, 1H, J ) 7.2 Hz), 2.99∼2.92 (m,
1H), 2.61 (ABX, 1H, JAB) 16.1 Hz, JAX) 5.6 Hz), 2.38 (ABX,
1H, JAB) 16.1 Hz, JAX) 12.0 Hz), 2.18 (s, 3H), 1.46 (s, 9H). 13
C
NMR (100 MHz, CDCl3): δ 195.1, 170.5, 168.9, 154.5, 149.5,
128.0, 84.7, 62.4, 53.1, 47.1, 38.5, 35.5, 28.1, 23.7. IR (thin film,
cm-1): 2980, 1790, 1750, 1670, 1304, 1148. HRMS (ESI+) for
[M + Na]+ C16H21NO6Na: calcd, 346.1261; found, 346.1257; [R]25
) -41.6 (c 1.53, CHCl3).
D
(1S,3rS,8rS,Z)-2-tert-Butyl-1-methyl 4-methyl-3,7-dioxo-3,-
3a,8,8a-tetrahydro-1H-oxepino[4,5-c]pyrrole-1,2(7H)-dicarboxy-
late (34). To a solution of the enone compound 33 (1.8 g, 5.5 mmol)
in CH2Cl2 (55 mL, 0.1M), was added m-CPBA (1.9 g, 11 mmol)
364.0844; [R]25 ) +27.1 (c 1.33, CHCl3).
D
Et3N (0.77 g, 1.1 mL, 7.6 mmol), Boc-anhydride (2.7 g, 12.6
mmol) and DMAP (0.77 g, 6.3 mmol) were added to a solution of
10120 J. Org. Chem., Vol. 72, No. 26, 2007