R. Chênevert et al. / Tetrahedron: Asymmetry 20 (2009) 1191–1196
1195
4.3.6. (R)-1-Phenylethyl benzoate 3f
400 MHz) d 1.10 (s, 9H), 2.43 (s, 3H), 3.27 (quint, J = 6.5 Hz, 1H),
4.25 (m, 4H), 5.05 (s, 2H), 6.88 (d, J = 8.6 Hz, 2H), 7.03 (d,
J = 8.6 Hz, 2H), 7.33–7.45 (m, 7H); 7.69 (d, J = 8.2 Hz, 2H); 13C
NMR (100 MHz, CDCl3) d 21.8, 27.2, 38.9, 43.5, 64.3, 70.2, 70.5,
115.3, 127.7, 128.2, 128.3, 128.9, 129.3, 129.6, 130.1, 132.9,
137.1, 145.1, 158.4, 178.3; HRMS (ES) calcd for C28H36NO6S
(M+H)+: 496.1919. Found: 496.1914.
Eluent: hexanes–EtOAc, 7:1; ½a D23
¼ ꢀ23 (c 1.2, EtOH), ee = 92%
ꢁ
(HPLC, Chiralcel OD-H, hexanes–0.5% isopropyl alcohol); IR (neat)
3090–2933, 1734, 1645, 1452, 1268, 1139, 711 cmꢀ1 1H NMR
;
(CDCl3, 400 MHz) d 1.69 (d, J = 6.5 Hz, 3H), 6.15 (q, J = 6.6 Hz, 1H),
7.29–7.59 (m, 8H), 8.10 (d, J = 7.8 Hz, 2H); 13C NMR (CDCl3,
100 MHz) d 22.9, 73.1, 126.3, 128.1, 128.6, 128.8, 129.9, 130.7,
133.1, 166.1.
4.6. Synthesis of phoracantholides I (R)-10 and J (R)-11
4.3.7. (R)-1-Phenylethyl cinnamate 3g
Eluent: hexanes–EtOAc, 7:1;
ee P 98% (HPLC, Chiralcel OD-H, hexanes–1% isopropyl alcohol);
IR (neat) 3062–2932, 1711, 1449, 1304, 1169 cmꢀ1 1H NMR
(CDCl3, 400 MHz) d 1.63 (d, J = 6.5 Hz, 3H), 6.03 (q, J = 6.5 Hz, 1H),
6.49 (d, J = 16.0 Hz, 1H), 7.30–7.44 (m, 8H), 7.52–7.55 (m, 2H),
7.71 (d, J = 16.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 22.5, 72.2,
118.6, 126.3, 128.1, 128.3, 128.7, 129.1, 130.5, 134.6, 141.9,
145.1, 166.4.
½
a 2D3
ꢁ
¼ ꢀ39 (c 1.5, CHCl3),
4.6.1. 1-Ethoxyvinyl pent-4-enoate 8
To a solution of 4-pentenoic acid (3.51 g, 35 mmol) and Ben-
nett’s ruthenium complex ([RuCl2(p-cymene)]2) (0.117 g,
0.18 mmol) in anhydrous diethyl ether (230 mL) at 0 °C under an
argon atmosphere, was added dropwise a solution of ethoxy acet-
ylene (4.00 g, 57.1 mmol) in anhydrous diethyl ether. The mixture
was stirred for 24 h at room temperature and the solvent was
evaporated. The crude product was purified by distillation (bp
100 °C, 1 mm Hg) to yield 7 (3.57 g, 60%) as a colorless oil. IR (neat)
;
4.3.8. (R)-1-Phenylethyl 2-(tert-butoxycarbonylamino)acetate
3081, 2984, 2934, 1773, 1674, 1240, 1132, 1046 cmꢀ1 1H NMR
;
3h
(CDCl3, 400 MHz) d 1.29 (t, J = 8.0 Hz, 3H), 2.34–2.41 (m, 2H),
2.47–2.53 (m, 2H), 3.72 (dd, J = 4.0 and 20.0 Hz, 2H), 3.83 (q,
J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz) d 14.3, 28.7, 33.4, 65.0,
71.9, 116.1, 136.4, 157.4, 170.5; HMRS (ES) calcd for C9H18NO3
(M+NH4)+: 188.12812. Found 188.12782.
Eluent: hexanes–EtOAc, 5:1;
ee P 98% (HPLC, Chiralcel OD-H, hexanes–2% isopropyl alcohol);
IR (neat) 3415, 3085, 2873, 1700, 1452, 1203, 1166 cmꢀ1 1H
NMR (CDCl3, 400 MHz) d 1.40 (s, 9H), 1.50 (d, J = 6.5 Hz, 3H), 3.84
(dq, J = 18.0 and 5.8 Hz, 2H), 5.29 (m, 1H), 5.88 (q, J = 6.5 Hz, 1H),
7.22–7.27 (m, 5H), 13C NMR (CDCl3, 100 MHz) d 22.3, 28.5, 42.8,
73.5, 79.8, 126.3, 128.2, 128.7, 141.3, 156.0, 169.9; HRMS (ES) calcd
for C15H21NO4Na (M+Na)+: 302.1363. Found 302.1401.
½
a 2D3
ꢁ
¼ þ15:0 (c 1.15, CHCl3),
;
4.6.2. Resolution of ( )-7: (R)-hept-6-en-yl pent-4-enoate (R)-9
and (S)-hept-6-en-2-ol (S)-7
To a solution of ( )-7 (0.246 g, 2.16 mmol) in toluene (6 mL)
were added 1-ethoxyvinyl pent-4-enoate (0.367 g, 2.16 mmol)
and lipase B from C. antarctica (CAL-B, 35 mg). The kinetic resolu-
tion was monitored by chiral GC. At the 50% completion point,
the mixture was filtered through Celite and concentrated in vacuo.
The crude product was purified by flash chromatography (CH2Cl2,
0–10% EtOAc) to give pure (R)-9 (0.188 g, 44%, ee = 95%) and (S)-
4.3.9. (R)-1-Phenylethyl 2-(phenylthio)acetate 3i
Eluent: hexanes–EtOAc, 10:1; ½a D23
¼ þ49 (c 3, CHCl3), ee = 94%
ꢁ
(HPLC, Chiralcel OD-H, hexanes–2% isopropyl alcohol); IR (neat)
3061–2931, 1731, 1270, 1130 cmꢀ1 1H NMR (CDCl3, 400 MHz) d
;
1.50 (d, J = 6.6 Hz, 3H), 3.65 (d, J = 1.8 Hz, 2H), 5.88 (q, J = 6.6 Hz,
1H), 7.21–7.37 (m, 10H), 13C NMR (CDCl3, 100 MHz) d 22.2, 37.2,
73.8, 126.4, 127.2, 128.2, 128.7, 129.2, 130.3, 135.1, 141.2, 169.2.
7 (0.113 g, 46%, ee = 98%) as colorless oils. (S)-7: ½a D23
¼ þ10:2 (c
ꢁ
1.2, CHCl3); lit.35a
½
a 2D0
ꢁ
¼ þ10:4 (c 0.79, CHCl3); lit.35b
½
a 2D3
a 2D3
ꢁ
¼ ꢀ10:8 (c 0.82, CHCl3) for the (R)-enantiomer. (R)-9:
4.4. (2R)-2-(4-(Benzyloxy)phenyl)-3-hydroxypropyl pivalate (R)-5
½
ꢁ
¼ ꢀ5:5 (c 2.06, CHCl3); IR (neat) 3079, 2978, 2936, 2863,
1733, 1641, 1256, 1178 cmꢀ1
;
1H NMR (CDCl3, 400 MHz) d 1.17
To a solution of 4 (200 mg, 0.825 mmol) and vinyl pivalate
(0.125 mL, 1.03 mmol) in diethyl ether (10 mL) was added A. niger
lipase (1000 units) and the mixture was stirred at room tempera-
ture. The progress of the reaction was monitored by HPLC. The
reaction was quenched by filtration of the enzyme and the volatiles
evaporated. The crude product was purified by flash chromatogra-
phy (hexanes–EtOAc, 2:1) to give (S)-5 (261 mg, 96%) as a white so-
(d, J = 6.0 Hz, 3H), 1.32–1.57 (m, 4H), 1.98–2.04 (m, 2H), 2.32–
2.35 (m, 4H), 4.85–5.04 (m, 5H), 5.69–5.81 (m, 2H); 13C NMR
(CDCl3, 100 MHz) d 20.2, 24.8, 29.2, 33.6, 34.0, 35.5, 70.9, 114.9,
115.6, 136.9, 138.6, 172.8; HRMS (ES) calcd for C12H20O2Na
(M+Na)+: 219.13555. Found 219.13427.
4.6.3. (R,Z)-10-Methyl-3,4,7,8,9,10-hexahydro-2H-oxecin-2-
one: phoracantholide J (R)-10
lid: mp 51–53 °C, lit.29 57 °C;
ee P 98% (HPLC, Chiralcel OD-H, hexanes–10% isopropyl alcohol);
IR (neat) 3429, 3033–2872, 1725, 1512, 1242, 1158 cmꢀ1 1H
½
a 2D3
ꢁ
¼ þ12:9 (c 0.64, CHCl3),
In an oven and flame-dried round-bottomed flask equipped
with a condenser containing second-generation Grubb’s catalyst
(81.5 mg, 10 mol %) were added methylene chloride (420 mL) and
compound 9 (0.1882 g, 0.96 mmol). The mixture was heated at re-
flux and monitored by TLC. When all the starting material was con-
sumed (3 days), the mixture was cooled to room temperature and
the methylene chloride was evaporated. The crude product was
immediately purified by flash chromatography (hexanes with 5%
;
NMR (CDCl3, 400 MHz) d 1.17 (s, 9H), 2.02 (br s, 1H), 3.13 (m,
1H), 3.81 (m, 2H), 4.34 (m, 2H), 5.06 (s, 2H), 6.96 (d, J = 8.6 Hz,
2H), 7.19 (d, J = 8.5 Hz, 2H), 7.33–7.45 (m, 5H); 13C NMR (CDCl3,
100 MHz) d 27.4, 39.1, 46.9, 64.1, 65.2, 70.3, 115.3, 127.7, 128.2,
128.8, 129.4, 131.4, 137.2, 158.2, 179.1.
4.5. (2S)-2-(4-Benzyloxy)phenyl)-3-(tosyloxy)propyl pivalate
(S)-6
AcOEt) to yield (R)-phoracantholide
J
ꢁ
9
as
¼ ꢀ32 (c 1.09, CHCl3);
¼ ꢀ40:3 (c 2.40,
a yellowish oil
(0.0548 g, 34%) and as the Z isomer. ½a D23
lit.33f
½
a 2D2:2
ꢁ
¼ ꢀ36:8 (c 1.77, CHCl3); lit.33a
½ ꢁ
a 2D3
To a solution of 5 (300 mg, 0.875 mmol) and triethylamine
(2 mL) in CH2Cl2 (40 mL) was added tosyl chloride (185 mg,
0.960 mmol) and the mixture was stirred at room temperature.
The progress of the reaction was monitored by TLC. The volatiles
were evaporated and the crude product was recrystallized in tolu-
ene–hexane for the X-ray diffraction analysis. IR (NaCl) 3065–
CHCl3); IR (neat) 2973, 2930, 2856, 1731, 1443, 1377, 1254,
1175, 1089, 969 cmꢀ1
;
1H NMR (CDCl3, 400 MHz) d 1.24 (d,
J = 6.8 Hz, 3H), 1.32–1.46 (m, 2H), 1.84–1.96 (m, 4H), 2.17–2.25
(m, 1H), 2.52 (dt, J = 4.0 and 14.4 Hz, 1H), 2.62–2.82 (m, 2H),
5.05–5.12 (m, 1H), 5.35 (td, J = 4.0 and 11.2 Hz, 1H), 5.41–5.49
(m, 1H); 13C NMR (CDCl3, 100 MHz) d 20.53, 25.82, 28.75, 32.17,
35.29, 35.49, 70.97, 129.81, 130.30, 173.13.
;
2872, 1727, 1611, 1513, 1363, 1177 cmꢀ1 1H NMR (CDCl3,