2366
A. Bracci et al.
PAPER
To a solution of the alcohol (0.102 g, 0.30 mmol) in THF (3.0 mL)
were added, at 0 °C, Et3N (0.049 mL, 0.32 mmol) and acetyl chlo-
ride (0.023 mL, 0.35 mmol). After 2 h, a buffer phosphate solution
(3 mL) was added and extracted with CH2Cl2. The combined organ-
ic layers were dried (Na2SO4), filtered and the solvent was removed
under reduced pressure. The residue was purified by flash chroma-
tography (EtOAc–petroleum ether, 2:8) to yield 13.
CH=CHCH3), 1.83 (m, 2 H, HCHCH2OAc, HCCH2CH2OAc), 2.10
(s, 3 H OCOCH3), 2.50 (m, 1 H, HCHCHCOO-t-Bu), 3.2 (s, 1 H,
NH), 3.75 (m, 1 H, CHCH=CHCH3), 3.90 (m, 1 H, CHCOO-t-Bu),
4.10 (m, 2 H, CH2OAc), 5.35 (m, 1 H, CH=CHCH3), 5.68 (m, 1 H,
CH=CHCH3).
13C NMR (100.6 MHz, HETCOR, CDCl3): = 131.4, 129.0, 63.9,
61.1, 60.0, 43.6, 36.9, 36.6, 31.6, 28.5, 21.6, 13.9.
Yield: 0.098 g (84%); colorless oil.
MS (FAB): m/z calcd for C16H27NO4: 297.19; found: 298.
1H NMR (200 MHz, CDCl3): = 1.50 [s, 9 H, C(CH3)3], 1.55 [s, 9
H, C(CH3)3], 1.70 (m, 1 H, HCHCH2OAc), 1.80 (m, 1 H, HCHCH-
COO-t-Bu), 1.90 (m, 1 H, HCHCH2OAc), 2.05 (s, 3 H, OCOCH3),
2.15 (m, 1 H, HCHCHCOO-t-Bu), 2.35 (m, 1 H, CHCH2CH2OAc),
3.40 (s, 3 H, OCH3), 4.10 (m, 2 H, CH2OAc), 4.15 (m, 1 H,
CHCOO-t-Bu), 5.01, 5.10 (2 m, 1 H, CHOCH3).
Anal. Calcd for C16H27NO4 (297.19): C, 64.62; H, 9.15; N, 4.71.
Found C, 64.70; H, 9.16; N, 4.70.
(2S,4R)-4-(2-Acetoxyethyl)-1-(2-benzyloxycarbonylaminopent-
4-enoyl)-5-propenylpyrrolidine-2-carboxylic Acid tert-Butyl
Ester (16)
13C NMR (50.3 MHz, CDCl3): = 171.7, 171.5, 154.4, 88.6, 81.0,
80.7, 63.2, 59.7, 56.7, 40.7, 33.7, 28.6, 28.4, 28.3, 21.1.
To a solution of ( )-N-(Z)-allylglycine (0.0526 g, 0.211 mmol) in
anhyd THF (0.5 mL) was added at –30 °C N-methylmorpholine
(0.0563 mL, 0.511 mmol) and isobutyl chloroformate (0.0293 mL,
0.224 mmol). After 30 min, 15 (0.019 g, 0.064 mmol) was added,
then the reaction mixture was stirred for 12 h. The suspension was
filtered on a Celite pad and the solvent was evaporated under re-
duced pressure. To the crude was added H2O and the mixture was
extracted with EtOAc. The combined organic layers were dried
(Na2SO4), filtered and the solvent was removed under reduced pres-
sure. The residue was purified by flash chromatography (EtOAc–
petroleum ether, 35:65) to yield 16.
MS (FAB): m/z calcd for C19H33NO7: 387.23; found: 388.
Anal. Calcd for C19H33NO7 (387.23): C, 58.90; H, 8.58; N, 3.61.
Found: C, 59.00; H, 8.60; N, 3.62.
(2S,4R)-4-(2-Acetoxyethyl)-5-[(Z)-propenyl]pyrrolidine-1,2-di-
carboxylic Acid tert-Butyl Ester (14)
To a vigorously stirred suspension of CuBr·DMS (0.114 g, 0.56
mmol) in anhyd Et2O (0.5 mL) was added a solution of (Z)-1-lithio-
1-propene (0.63 M in Et2O, 0.803 mL) via cannula at –50 °C under
an argon atmosphere. The resulting dark brown mixture was stirred
for 30 min at –50 °C before being cooled to –78 °C. BF3·Et2O
(0.074 mL, 0.56 mmol) was then added slowly. After 10 min, a so-
lution of 13 (0.098 g, 0.25 mmol) in anhyd Et2O (0.450 mL) was
then added dropwise via cannula. The black reaction mixture was
slowly allowed to warm to r.t. and stirred for 12 h. After this period
a mixture of sat. aq NH4Cl and concd NH4OH was then added. The
mixture was vigorously stirred for 45 min and extracted with
EtOAc. The combined organic layers were dried (Na2SO4), filtered
and the solvent was removed under reduced pressure. The residue
was purified by flash chromatography (EtOAc–petroleum ether,
2:8) to yield 14.
Yield: 0.020 g (61%); yellowish oil; [ ]D20 –9.5 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): = 1.48 [s, 9 H, C(CH3)3], 1.75 (m, 2
H, HCHCH2OAc, HCHCHCOOBu-t), 1.90 (m, 3 H, CH=CHCH3),
1.95 (m, 1 H, HCHCH2OAc), 2.10 (m, 4 H, HCCH2CH2OAc,
OCOCH3), 2.35 (m, 1 H, HCHCHCOO-t-Bu), 2.45 (m, 2 H,
CH2CHNHCbz), 4.10 (m, 2 H, CH2OAc), 4.32 (m, 1 H, CHCOO-t-
Bu), 4.60 (m, 1 H, CHNHCbz), 4.75 (m, 1 H, CHCH=CHCH3), 5.10
(m, 4 H, CH2Ph, CH=CH2), 5.30 (m, 1 H, NH), 5.40 (m, 1 H,
CH=CHCH3), 5.70 (m, 2 H, CH=CH2, CH=CHCH3), 7.35 (m, 5 H,
aromatics).
13C NMR (50.3 MHz, CDCl3): = 171.5, 171.0, 170.5, 157.0,
133.4, 131.2, 128.6, 128.1, 127.7, 118.3, 81.4, 66.9, 62.7, 61.3,
60.1, 51.3, 43.9, 33.1, 31.2, 28.0, 21.0, 13.5.
Yield: 0.064 (64%); yellowish oil; [ ]D20 +0.11 (c 1.03, CHCl3).
1H NMR (400 MHz, CDCl3): = 1.45 [s, 9 H, C(CH3)3], 1.50 [s, 9
H, C(CH3)3], 1.58 (m, 1 H, HCHCH2OAc), 1.60 (m, 1 H, HCHCH-
COO-t-Bu), 1.70 (m, 3 H, CH=CHCH3), 1.90 (m, 2 H,
HCHCH2OAc, HCCH2CH2OAc), 2.05 (s, 3 H OCOCH3), 2.40 (m,
1 H, HCHCHCOO-t-Bu), 4.10 (m, 2 H, CH2OAc), 4.20 (m, 1 H,
CHCOO-t-Bu), 4.38 (m, 1 H, CHCH=CHCH3), 5.30 (m, 1 H,
CH=CHCH3), 5.60 (m, 1 H, CH=CHCH3).
MS (FAB): m/z calcd for C29H40N2O7: 528.28; found: 529.
Anal. Calcd for C29H40N2O7 (528.28): C, 65.89; H, 7.63; N, 5.30.
Found C, 66.00; H, 7.64; N, 5.30.
(3S,7S,8R,10S)-1-Aza-2-oxo-3-benzyloxycarbonylamino-8-ace-
toxyethyl-10-carbo-tert-butoxybicyclo[5.3.0]decane (17)
To a solution of 16 (0.019 g, 0.0369 mmol) in anhyd CH2Cl2 (0.9
mL) under nitrogen was added Grubbs catalyst (0.004 g, 0.005
mmol). After stirring at 40 °C for 60 h, the solvent was evaporated
under reduced pressure. The crude was purified by flash chromatog-
raphy (EtOAc–petroleum ether, 35:65) to yield the cyclized prod-
uct.
13C NMR (100.6 MHz, HETCOR, CDCl3): = 131.5, 124.0, 63.1,
61.0, 60.5, 42.8, 34.3, 34.2, 31.6, 28.7, 28.3, 21.3, 13.7.
MS (FAB): m/z calcd for C21H35NO6: 397.25; found: 398.
Anal. Calcd for C21H35NO6 (397.25): C, 63.45; H, 8.87; N, 3.52.
Found C, 63.60; H, 8.88; N, 3.52.
Yield: 0.015 g (83%); yellowish oil; [ ]D20 –41.1 (c1.0, CHCl3).
(2S,4R)-4-(2-Acetoxyethyl)-5-[(Z)-propenyl]pyrrolidine-2-car-
boxylic Acid tert-Butyl Ester (15)
1H NMR (400 MHz, CDCl3): = 1.48 [s, 9 H, C(CH3)3], 1.70 (m, 1
H, HCHCHCOO-t-Bu ), 2.04 (m, 1 H, HCHCH2OAc), 2.08 (s, 3 H,
COCH3), 2.10 (m, 1 H, HCHCH2CH2OAc), 2.20 (m, 1 H, HCHCH-
NHCbz), 2.40 (m, 1 H, HCHCHCOO-t-Bu), 2.67 (m, 1 H,
HCHCH2OAc), 2.70 (m, 1 H, HCHCHNHCbz), 4.10 (m, 2 H,
CH2OAc), 4.30 (m, 2 H, CHCOO-t-Bu, CHCH=CH), 4.70 (m, 1 H,
CHNHCbz), 5.10 (m, 2 H, CH2Ph), 5.50 (m, 1 H, CHCH=CH), 5.7
(m, 1 H, CHCH=CH), 6.10 (m, 1 H, NH), 7.35 (m, 5 H, aromatics).
To a solution of 14 (0.034 g, 0.09 mmol) in t-BuOAc (0.85 mL), at
0 °C, HClO4 (0.077 mL, 0.13 mmol) was added. After 1 h, the reac-
tion was warmed to r.t. and stirred for 4 h, and then Et3N (0.6 mL)
was added. The mixture was extracted with EtOAc, the combined
organic layers were dried (Na2SO4), filtered and the solvent was re-
moved under reduced pressure. The residue was purified by flash
chromatography (EtOAc–petroleum ether, 8:2) to yield 15.
Yield: 79%; orange oil; [ ]D20 –6.7 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): = 1.48 [s, 9 H, C(CH3)3], 1.52 (m, 1
H, HCHCH2OAc), 1.55 (m, 1 H, HCHCHCOO-t-Bu), 1.76 (m, 3 H,
13C NMR (50.3 MHz, CDCl3): = 170.7, 170.2, 155.5, 136.6,
128.7, 128.6, 128.4, 128.2, 128.0, 81.9, 66.9, 62.4, 61.8, 61.3, 51.6,
44.2, 33.2, 32.2, 31.8, 31.1, 28.0, 21.1.
MS (FAB): m/z calcd for C26H34N2O7: 486.24; found: 487.
Synthesis 2003, No. 15, 2363–2367 © Thieme Stuttgart · New York