LETTER
Synthesis of Enantiomerically Pure Cyclopentene Building Blocks
487
10 mol%) in THF (20 mL) at –20 °C and stirred for 5 min.
(MeOH): lmax (lg e) = 251.5 (2.728), 257.5 (2.734), 263.0
(2.666) nm. IR (film): 3426, 3063, 2929, 2855, 1734, 1496,
1454, 1363, 1244, 1093, 1026, 937, 873, 835, 770, 737, 698
cm–1. 1H NMR (300 MHz, CDCl3): d = 0.24 [s, 6 H,
Monoacetate 7 (550 mg, 3.90 mmol) was added and the
reaction stirred for further 15 min. After addition of sat.
NH4Cl (20 mL) and aq NH3 (20 mL) the aqueous layer was
separated and extracted with EtOAc (3 × 70 mL). The
combined organic layers were dried (Na2SO4) and the
solvent removed under reduced pressure. Purification of the
residue by column chromatography (n-pentane–EtOAc, 3:1)
afforded benzyl ether 8 as a clear liquid (732 mg, 3.59 mmol,
92%); [a]D20 +146.3 (c 1.00, CHCl3); Rf = 0.17 (n-pentane–
EtOAc, 3:1). IR (KBr): 3380, 3060, 2856, 1651, 1496, 1453,
1361, 1074, 1028, 738, 698 cm–1. 1H NMR (300 MHz,
CDCl3): d = 1.75 (s, 1 H, OH), 1.81–2.01 (m, 2 H, H2-5),
3.12–3.24 (m, 1 H, H-4), 3.29–3.41 (m, 2 H, CH2OBn), 4.51
(s, 2 H, CH2Ph), 4.84–4.91 (m, 1 H, H-1), 5.89 (dt, J = 5.6,
2.2 Hz, 1 H, H-2), 5.97–6.01 (m, 1 H, H-3), 7.24–7.38 (m, 5
H, PhH). 13C NMR (75 MHz, CDCl3): d = 37.3, 44.8, 73.0,
73.9, 76.9, 127.5, 128.3, 134.3, 136.8, 138.3. MS (EI, 70
eV): m/z = 204.1 [M+]. HRMS (EI): m/z [M]+ calcd for
C13H16O2: 204.2649; found: 204.2649.
Si(CH3)2], 0.89 [s, 9 H, (SiC(CH3)3], 1.57–1.60 (m, 1 H, HA-
5), 2.40–2.52 (m, 1 H, HB-5), 2.80–2.96 (m, 1 H, H-4), 3.25–
3.60 (m, 4 H, CH2OBn, H2-2¢) 4.51 (s, 2 H, CH2Ph), 5.59–
5.65 (m, 1 H, H-1), 5.80–6.08 (m, 2 H, H-2, H-3). 13C NMR
(75 MHz, CDCl3): d = –3.62, 17.94, 25.60, 33.57, 44.78,
69.40 73.08, 74.04, 79.49, 127.56, 128.33, 130.48, 138.13,
138.27, 160.51. MS (DCI): m/z (%) = 378.4 (12) [M +
+
+
NH4 ], 361.4 (4) [M + H+], 264.2 (100) [C15H18O3 + NH4 ].
(13) Synthesis of 11.
A solution of crude silyl ketene acetal 10 (7.45 g, 20.7
mmol) in dry xylene (50 mL) was heated in a sealed tube to
180 °C for 18 h. After cooling to ambient temperature the
solvent was removed under reduced pressure and the residue
dissolved in THF (60 mL). Then, aq NaOH (2 M, 60 mL)
was added and the reaction stirred vigorously for 2 h.
Pentane was then added (100 mL) and the mixture extracted
with aq NaOH (2 M, 3 × 150 mL). The combined aqueous
layers were acidified to pH 1 with HCl (6 M) and extracted
with EtOAc (3 × 200 mL). The combined organic layers
were dried over Na2SO4 and the solvent evaporated under
reduced pressure. Purification of the residue by column
chromatography (pentane–EtOAc, 6:1 + 0.5% AcOH) gave
(11) Synthesis of 9.
DIAD (3.94 g, 19.5 mmol) was added dropwise to a stirred
solution of benzyl ether 8 (1.98 g, 9.74 mmol), Ph3P (5.12
g, 19.5 mmol) and AcOH (2.23 mL, 2.34 g, 39.0 mmol) in
Et2O (60 mL) at 0 °C. After stirring for 30 min at 0 °C the
reaction was filtered and the filtrate was washed with cold
pentane (4 × 100 mL). The combined extracts were washed
with sat. NaHCO3 (100 mL) and the aqueous layer was
separated and extracted with pentane (2 × 100 mL). The
combined extracts were dried (Na2SO4) and evaporated
under reduced pressure. Purification of the residue by
column chromatography (PE–EtOAc, 20:1) gave acetate 9
as a colorless oil (4.56 g, 18.5 mmol, 95%); [a]D20 –1.10 (c
1.00, CHCl3); Rf = 0.24 (n-pentane–EtOAc, 15:1). UV/Vis
(MeOH): lmax (lg e) = 204.5 (3.926), 251.0 (2.324), 257.0
(2.304), 263.0 (2.140) nm. IR (film): 3391, 3064, 2857,
1732, 1496, 1454, 1364, 1243, 1202, 1092, 1025, 907, 740,
708 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.54 (dt,
J = 14.3, 4.1 Hz, 1 H, HA-5), 1.99 (s, 3 H, CH3), 2.46 (dt,
J = 14.3, 7.9 Hz, 1 H, HB-5), 2.92 (mc, 1 H, H-4), 3.33–3.46
(m, 2 H, CH2OBn), 4.52 (s, 2 H, CH2Ph), 5.59–5.66 (m, 1 H,
H-1), 5.84 (dt, J = 5.7, 2.3 Hz, 1 H, H-2), 6.03–6.07 (m, 1 H,
H-3), 7.25–7.37 (m, 5 H, PhH). 13C NMR (50 MHz, CDCl3):
d = 21.26, 33.59, 44.79, 73.08, 74.05, 79.47, 127.55, 127.57,
128.33, 130.49, 138.13, 138.30, 170.85. MS (EI, 70 eV):
m/z (%) = 246.2 (1) [M+], 203.1 (4) [M – C2H3O+], 186.1
20
acid 11 as a pale yellow oil (4.43 g, 18.0 mmol, 87%); [a]D
+76.1 (c 1.00, CHCl3); Rf = 0.34 (n-pentane–EtOAc, 5:1, 6%
AcOH). UV/Vis (MeOH): lmax (lg e) = 251.5 (2.265), 257.5
(2.321), 263.5 (2.201) nm. IR (film): 3060, 2926, 1706,
1496, 1453, 1410, 1364, 1276, 1200, 1098, 1028, 935, 735,
698 cm–1. 1H NMR (200 MHz, CDCl3): d = 2.04–2.14 (m, 1
H, HB-4¢), 2.21 (dd, J = 15.6, 9.0 Hz, 1 H, HB-2), 2.32–2.46
(m, 1 H, HA-4¢), 2.58 (dd, J = 15.6, 6.5 Hz, 1 H, HA-2), 2.70
(mc, 1 H, H-5¢), 3.13–3.24 (m, 1 H, H-1¢), 3.42–3.52 (m, 2 H,
CH2OBn), 4.49 (s, 2 H, CH2Ph), 5.72–5.75 (m, 2 H, H-2¢, H-
3¢), 7.24–7.38 (m, 5 H, Ph-H). 13C NMR (50 MHz, CDCl3):
d = 34.60, 34.89, 40.01, 42.32, 70.58, 73.01, 127.55, 127.65,
128.33, 130.38, 133.71, 138.10, 179.39. MS (EI, 70 eV):
+
m/z (%) = 246.2 (4) [M+], 91 (100) [C7H7 ]. HRMS (ESI):
m/z [M + Na]+ calcd for C15H18NaO3: 269.11482; found:
269.11487.
(14) Synthesis of 2.
BCl3 (ca. 1 M in CH2Cl2, 2.0 mL, 2.0 mmol) was added
dropwise to a solution of acid 11 (246 mg, 1.00 mmol) in
CH2Cl2 (10 mL) at –40 °C. The reaction was allowed to
warm to 0 °C while being continuously stirred for 2 h. After
being stirred for a further 15 min at 0 °C sat. NH4Cl (5 mL)
was added, the aqueous layer was separated and extracted
with CH2Cl2 (3 × 50 mL). The combined organic extracts
were dried (Na2SO4), filtered and evaporated under reduced
pressure. After purification of the residue by column
chromatography (n-pentane–Et2O, 1:1) 2 was obtained as a
white solid (124 mg, 890 mmol, 89%); [a]D20 +51.0 (c 0.30,
CH2Cl2); Rf = 0.22 (n-pentane–Et2O, 1:1). IR (KBr): 3444,
3052, 2994, 2900, 2854, 1742, 1484, 1435, 1386, 1358,
1340, 1280, 1232, 1078, 991, 950, 861, 758, 724 cm–1. 1H
NMR (300 MHz, CDCl3): d = 2.21–2.31 (m, 1 H, HB-7),
2.25 (dd, J = 15.0, 7.2 Hz, 1 H, HB-4), 2.62–2.86 (m, 2 H, 7-
HA, H-7a), 2.66 (dd, J = 15.0, 6.4 Hz, 1 H, HA-4), 3.26–3.40
(m, 1 H, H-4a), 4.10 (dd, J = 11.3, 6.4 Hz, 1 H, HA-1) 4.30
(dd, J = 11.3, 4.3 Hz, 1 H, HB-1), 5.56 and 5.76 (2 × mc, 2 ×
1 H, H-5, H-6). 13C NMR (75 MHz, CDCl3): d = 33.79,
33.87, 41.84, 70.27, 130.88, 131.79, 173.37. MS (EI, 70 eV):
m/z = 138 (6) [M+], 66.0(100) [C6H6]+. HRMS (EI): m/z
[M]+ calcd for C8H10O2: 138.0681; found: 138.0681.
+
+
(12) [M – C2H4O2 ], 91 (100) [C7H7 ]. HRMS (ESI): m/z [M
+ Na]+ calcd for C8H10NaO2: 269.11482; found: 269.11473.
(12) Synthesis of 10.
n-BuLi (2.5 M in hexane, 12.0 mL, 29.9 mmol) was added
dropwise to a stirred solution of DIPA (4.33 mL, 3.10 g, 31.0
mmol) in THF (20 mL) at 0 °C. After 5 min HMPA (5 mL)
was added and the reaction was cooled to –78 °C and stirred
for further 10 min whereupon a solution of acetate 9 (5.08 g,
20.7 mmol) in THF (35 mL) was added dropwise. The
reaction was maintained at –78 °C for additional 20 min. A
solution of TBSCl (4.07 g, 27.0 mmol) in THF (5 mL) was
added and the reaction was stirred at –78 °C for 5 min before
warming to r.t. Then pentane (150 mL) and aq NaOH (0.1 M,
150 mL) were added. The aqueous layer was separated and
extracted with pentane (2 × 150 ml). The combined pentane
extracts were washed with aq NaOH (0.1 M, 2 × 100 mL),
H2O (100 mL), dried (Na2SO4) and the solvent evaporated to
give the title compound as a yellow oil (7.45 g, 20.7 mmol,
quant.) which was used without further purification steps for
the next reaction; [a]D20 +18.5 (c 1.00, CHCl3). UV/Vis
Synlett 2007, No. 3, 485–487 © Thieme Stuttgart · New York