1162
Y. Matsuda et al. / Tetrahedron 70 (2014) 1154e1168
128.3, 138.5, 138.6, 142.4, 142.6, 173.7, 173.8; LRMS (EI) m/z (M)þ
588.4; HRMS (EI-quadrupole) m/z (M)þ calcd for C35H60O5Si
588.4210, found 588.4192. Compound 33: Rf¼0.50 (hexane/
EtOAc¼5:1); IR (neat, cmꢂ1) 3443, 2954, 2929, 2875, 2857, 1733,
1456, 1436, 1415, 1362, 1237, 1201, 1157, 1103, 1011, 913, 737, 698;
454.3; HRMS (EI-quadrupole) m/z (M)þ calcd for C29H42O4
454.3083 found 454.3082.
4.2.4. (ꢃ)-(1S,5R,9R)-Methyl 7-(3-benzyloxypropyl)-1-hexyl-9-
vinyl-6-oxaspiro[4.5]dec-7-ene-8-carboxylate (35). To a stirred so-
lution of 33 (64.8 mg, 0.110 mmol) in CH2Cl2 (1.10 mL) was added
PCC (47.4 mg, 0.220 mmol) at room temperature. After 8 h, the
mixture was directly purified by column chromatography on silica
gel (1.50 g, hexane/EtOAc¼10:1) to afford 35 (20.0 mg, 40%) as
1H NMR (500 MHz, CDCl3, TMS¼0.00)
0.56 (q, J¼8.0 Hz, 6H), 0.88
d
(t, J¼7.2 Hz, 3H), 0.93 (t, J¼8.0 Hz, 9H), 0.95 (m, 1H), 1.10e1.17 (m,
2H), 1.22e1.34 (m, 8H), 1.41e1.54 (m, 4H), 1.64e1.99 (m, 6H), 2.49
(dd, J¼8.9, 4.6 Hz, 1H), 2.55 (ddd, J¼7.1, 7.1, 1.7 Hz, 1H), 2.62 (br d,
J¼5.1 Hz, 1H), 2.79 (br d, J¼9.7 Hz, 1H), 2.83 (m, 1H), 2.94 (dddd,
J¼8.9, 8.7, 4.6, 4.6 Hz, 1H), 3.45 (m, 1H), 3.48e3.52 (m, 2H), 3.66 (s,
2.27H), 3.70 (s, 0.53H), 3.84 (m, 1H), 4.44e4.51 (m, 2H), 5.00 (dd,
J¼10.1, 2.0 Hz, 0.82H), 5.07 (dd, J¼17.4, 2.0 Hz, 0.82H), 5.08 (d,
J¼1.4 Hz, 0.18H), 5.12 (d, J¼1.7 Hz, 0.18H), 5.60 (ddd, J¼17.2, 10.0,
10.0 Hz, 0.18H), 5.90 (ddd, J¼17.4, 10.1, 8.7 Hz, 0.82H), 7.27e7.36
a colorless syrup: Rf¼0.72 (hexane/EtOAc¼5:1); IR (neat, cmꢂ1
)
2954, 2928, 2856, 1707, 1612, 1454, 1437, 1271, 1089, 913, 737, 698;
1H NMR (500 MHz, benzene-d6, solvent residual peak¼7.16)
d 0.75
(m, 1H), 0.92 (t, J¼7.2 Hz, 3H), 1.10 (m, 1H), 1.22e1.34 (m, 9H), 1.41
(m, 1H), 1.49 (m, 1H), 1.56 (dd, J¼13.7, 4.6 Hz, 1H), 1.66 (m, 1H), 1.75
(m, 1H), 1.75 (dd, J¼13.7, 7.1 Hz, 1H), 1.91 (m, 1H), 1.94 (m, 1H), 2.04
(m, 1H), 2.14 (m, 1H), 2.90 (m, 1H), 3.06 (ddd, J¼13.2, 9.2, 5.8 Hz,
1H), 3.48 (t, J¼6.6 Hz, 2H), 3.49 (s, 3H), 3.54 (m, 1H), 4.36 (s, 2H),
5.00 (ddd, J¼10.2, 1.4, 1.4 Hz, 1H), 5.14 (ddd, J¼16.9, 1.7, 1.4 Hz, 1H),
5.81 (ddd, J¼16.9, 10.2, 6.3 Hz, 1H), 7.08 (m, 1H), 7.14e7.18 (m, 2H),
7.30e7.32 (m, 2H); 13C NMR (125 MHz, benzene-d6, benzene-
(m, 4H); 13C NMR (125 MHz, CDCl3, CDCl3¼77.00)
d 6.7, 7.3, 14.1,
19.7, 19.9, 22.7, 26.1, 28.2, 28.6, 29.4, 29.8, 31.9, 32.6, 37.6, 37.7,
38.6, 50.4, 51.2, 57.4, 70.2, 70.4, 73.0, 85.2, 115.2, 127.5, 127.6, 127.7,
128.4, 130.2, 140.9, 173.6; LRMS (EI) m/z (M)þ 588.4; HRMS (EI-
quadrupole) m/z (M)þ calcd for C35H60O5Si 588.4210, found
588.4210.
d6¼128.06)
d 14.4, 21.9, 23.1, 28.4, 28.7, 28.8, 29.9, 30.1, 30.6, 32.3,
32.8, 35.4, 36.6, 48.5, 50.7, 70.3, 72.9, 88.7, 103.6, 114.2, 127.5 (2C),
128.4 (2C), 128.5, 139.6, 142.8, 165.5, 168.6; LRMS (EI) m/z (M)þ
454.4; HRMS (EI-quadrupole) m/z (M)þ calcd for C29H42O4
454.3083, found 454.3075.
4.2.2. (ꢃ)-(1S,5R,9S)-8-(4-(Benzyloxy)-1-hydroxybutyl)-1-hexyl-9-
vinyl-6-oxaspiro[4.5]decan-7-one (34). To a stirred solution of 23
(25.6 mg, 0.0435 mmol) in THF (0.435 mL) was added 1.0 M TBAF in
THF (0.0870 mL, 0.0870 mmol) at room temperature. After 1 h,
saturated aqueous NH4Cl solution was added at 0 ꢁC and the mix-
ture was extracted with EtOAc. The organic layer was washed with
saturated aqueous NaCl solution, dried over Na2SO4, and concen-
trated under reduced pressure. The residue was purified by column
chromatography on silica gel (1.0 g, hexane/EtOAc¼5:1) to afford 34
(13.1 mg, 68%) as a colorless syrup: Rf¼0.51 (hexane/EtOAc¼5:1); IR
(neat, cmꢂ1) 3440, 2954, 2928, 2856, 1699, 1454, 1364, 1266, 1204,
1102, 1028, 994, 968, 919, 735, 698; 1H NMR (500 MHz, CDCl3,
4.2.5. Ethyl (3S,2Z,4E)-3-hydroxy-2-(iodomethylene)hex-4-enoate
(42). To a stirred solution of oxazaborolidinium catalyst 41a
(120 mg, 0.339 mmol) in CH2Cl2 (1.41 mL) was added at ꢂ40 ꢁC
AlBr3 (58.5 mg, 0.282 mmol). After 20 min at ꢂ40 ꢁC, a pale yellow
homogeneous catalyst solution was obtained. The catalyst solution
was cooled to ꢂ78 ꢁC and crotonaldehyde (0.120 mL, 1.41 mmol)
was then added dropwise to the mixture. After 20 min stirring at
ꢂ78 ꢁC, ethyl propiolate (0.358 mL, 3.53 mmol) and TMSI
(0.442 mL, 2.82 mmol) were added sequentially and quickly to the
mixture. After 24 h at ꢂ78 ꢁC, water was added and the mixture
was extracted with CH2Cl2. The organic layer was washed with
saturated aqueous NaCl solution, dried over Na2SO4, and concen-
trated under reduced pressure. The residue was purified by column
chromatography on silica gel (20.0 g, hexane/EtOAc¼4:1) to afford
4222b (334 mg, 80%, 56% ee) as a yellow syrup: Rf¼0.51 (hexane/
TMS¼0.00)
d
0.88 (t, J¼6.9 Hz, 3H), 1.02 (m, 1H), 1.18e1.39 (m, 9H),
1.45e1.52 (m, 2H), 1.62e1.82 (m, 7H), 1.87e1.96 (m, 2H), 1.99e2.08
(m, 2H), 2.52 (m, 1H), 2.57 (dd, J¼11.2, 3.1 Hz, 1H), 3.46e3.56 (m,
2H), 3.75 (br s, 1H), 3.77 (br s, 1H), 3.84 (m, 1H), 4.47e4.52 (m, 2H),
5.11 (br d, J¼10.3 Hz, 1H), 5.12 (br d, J¼16.9 Hz, 1H), 5.65 (ddd,
J¼16.9, 10.3, 7.7 Hz, 1H), 7.27e7.35 (m, 4H); 13C NMR (125 MHz,
CDCl3, CDCl3¼77.00)
d 14.1, 21.2, 22.6, 26.5, 28.1, 28.9, 29.4, 29.5,
29.6, 31.8, 34.6, 36.2, 37.9, 49.6, 51.3, 69.8, 70.5, 72.8, 93.2, 116.8,
127.5,127.6, 127.7,128.3 (2C),138.5,139.6,173.9; LRMS (EI) m/z (M)þ
442.4; HRMS (EI-quadrupole) m/z (M)þ calcd for C28H42O4
442.3083, found 442.3088.
EtOAc¼3:1); ½a D20:1
ꢄ
þ2.35 (c 1.00, CHCl3); 1H NMR (CDCl3, 500 MHz,
TMS¼0.00)
d
1.36 (t, J¼7.0 Hz, 3H), 1.70 (d, J¼6.6 Hz, 3H), 2.77 (d,
J¼6.0 Hz, 1H), 4.31 (q, J¼7.0 Hz, 2H), 4.88 (m, 1H), 5.50 (ddq, J¼15.4,
6.6, 1.2 Hz, 1H), 5.78 (ddq, J¼15.4, 6.6, 1.0 Hz, 1H), 7.18 (d, J¼1.2 Hz,
1H).
4.2.3. (ꢃ)-(1S,5R,9S)-Methyl 7-(3-benzyloxypropyl)-1-hexyl-9-vinyl-
6-oxaspiro[4.5]dec-7-ene-8-carboxylate (22). To a stirred solution
of 23 (59.0 mg, 0.100 mmol) in CH2Cl2 (1.00 mL) was added PCC
(43.2 mg, 0.200 mmol) at room temperature. After 8 h, the mix-
ture was directly purified by column chromatography on silica gel
(1.0 g, hexane/EtOAc¼10:1) to afford 22 (19.1 mg, 42%) as a color-
less syrup: Rf¼0.72 (hexane/EtOAc¼5:1); IR (neat, cmꢂ1) 2953,
2928, 2856, 1710, 1641, 1615, 1454, 1434, 1268, 1188, 1096, 912, 735,
698; 1H NMR (500 MHz, benzene-d6, solvent residual peak¼7.16)
4.2.6. Ethyl
(S,2Z,4E)-3-(tert-butyldimethylsilyloxy)-2-(iodo-
methylene)hex-4-enoate (43). To a stirred solution of 42 (70.0 mg,
0.236 mmol, 56% ee) in DMF (0.788 mL) were added imidazole
(32.2 mg, 0.473 mmol) and TBSCl (53.4 mg, 0.355 mmol) at room
temperature. After 1 h at room temperature, saturated aqueous
NH4Cl solution was added and the mixture was extracted with
hexane. The organic layer was washed with saturated aqueous NaCl
solution, dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel (2.9 g, hexane/EtOAc¼5:1) to afford 43 (92.2 mg, 95%) as
d
0.81 (m, 1H), 0.91 (t, J¼7.1 Hz, 3H), 1.06e1.14 (m, 2H), 1.20e1.30
(m, 7H), 1.32e1.45 (m, 3H), 1.35 (m, 1H), 1.52e1.61 (m, 2H), 1.56
(m, 1H), 1.70 (m, 1H), 1.91 (m, 1H), 1.96e2.11 (m, 2H), 2.80 (ddd,
J¼14.6, 9.2, 5.8 Hz, 1H), 3.13 (ddd, J¼14.6, 8.6, 6.6 Hz, 1H), 3.34 (dt,
J¼9.2, 7.7 Hz, 1H), 3.44 (t, J¼6.6 Hz, 2H), 3.50 (s, 3H), 4.34 (s, 2H),
5.02 (dd, J¼10.0, 1.1 Hz, 1H), 5.18 (br d, J¼17.7 Hz, 1H), 5.76 (ddd,
J¼17.7, 10.0, 7.7 Hz, 1H), 7.08 (m, 1H), 7.15e7.18 (m, 2H), 7.30 (d,
J¼6.9 Hz, 2H); 13C NMR (125 MHz, benzene-d6, benzene-
a yellow syrup: Rf¼0.75 (hexane/EtOAc¼3:1); ½a D24:2
þ2.3 (c 0.50,
ꢄ
CHCl3); IR (neat, cmꢂ1) 2957, 2931, 2887, 2858, 1728, 1472, 1464,
1367, 1304, 1275, 1257, 1183, 1097, 1039, 965, 871, 837, 778; 1H NMR
(CDCl3, 500 MHz, CDCl3, solvent residual peak¼7.26)
d 0.047 (s, 3H),
0.053 (s, 3H), 0.88 (s, 9H), 1.33 (t, J¼7.1 Hz, 3H), 1.67 (dd, J¼6.6,
0.7 Hz, 3H), 4.21e4.32 (m, 2H), 4.91 (br d, J¼7.1 Hz, 1H), 5.36 (ddq,
J¼15.5, 7.2, 0.7 Hz, 1H), 5.65 (ddq, J¼15.5, 6.6, 1.0 Hz, 1H), 6.99 (d,
d6¼128.06)
d 14.4, 21.5, 23.1, 28.6, 28.6, 29.7, 30.0, 30.1, 30.2, 32.3,
34.4, 35.5, 36.2, 48.6, 50.5, 70.2, 72.9, 87.8, 105.0, 114.4, 127.5 (2C),
J¼1.7 Hz, 1H); 13C NMR (125 MHz, CDCl3, CDCl3¼77.00)
ꢂ5.1, ꢂ4.5,
d
127.8 (2C), 128.5, 139.6, 142.2, 164.5, 168.5; LRMS (EI) m/z (M)þ
14.1, 17.6, 18.2, 25.8 (3C), 61.1, 75.2, 81.9, 127.9, 131.0, 147.2, 166.2;