6
A. Kamal et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
60%) and benzyl bromide (1 mL, 8.40 mmol) at 0 °C, and allowed to
stir at room temperature for 4 h. After completion of the reaction, it
was quenched with a saturated NH4Cl solution (20 mL). Next, the
THF was evaporated, extracted with CHCl3 (2 ꢂ 40 mL), dried over
anhydrous Na2SO4, and concentrated under reduced pressure. The
residue was purified by column chromatography (silica gel, 60–
120 mesh, EtOAc/hexane 5:95) to afford 18 (1.95 g, 87%) as a yel-
4.1.11. (5S,6R)-5-(Benzyloxy)undec-1-en-6-ol 21
To a stirred solution of 20 (0.6 g, 2.75 mmol) and CuI (catalytic
amount) in dry THF (20 mL) was slowly added butyl magnesium
chloride {freshly prepared with Mg (0.164 mg, 6.83 mmol), n-butyl
chloride (0.77 mL, 7.37 mmol) and I2 (2 mg) in dry THF (20 mL)} at
ꢀ35 °C under a nitrogen atmosphere. Next, the reaction mixture
was stirred for 3 h at the same temperature. After 3 h, the reaction
was quenched with a saturated NH4Cl solution (20 mL) at 0 °C,
then THF was evaporated and extracted with ethyl acetate
(2 ꢂ 30 mL). The combined organic layers were dried over anhy-
drous Na2SO4 and concentrated in vacuo. The residue was purified
by column chromatography (silica gel, 60–120 mesh, EtOAc/hex-
ane 10:90) to afford compound 21 (0.615 g, 81%) as a liquid.
low oil. ½a 2D6:8
ꢃ
¼ þ0:02 (c 0.109, CHCl3); IR (neat):
cmax: 2936,
2859, 1449, 1103, 929, 738, 698 cmꢀ1
;
1H NMR (600 MHz, CDCl3):
7.34 (m, 4H), 7.29 (m, 1H), 5.81 (m, J = 16.94, 6.4 Hz, 1H), 5.02 (dd,
J = 17.3, 1.5 Hz, 1H), 4.97 (d, J = 10.6 Hz, 1H), 4.67 (d, J = 11.29 Hz,
1H), 4.59 (d, J = 11.29 Hz, 1H), 4.10 (q, J = 12.04, 6.4 Hz, 1H), 4.03
(t, J = 6.4, Hz, 1H), 3.89 (t, J = 7.5 Hz, 1H), 3.57 (q, J = 6.4, 5.64 Hz,
1H), 2.24 (m, 1H), 2.16 (m, 1H), 1.68–1.55 (m, 10H), 1.4 (br s,
2H); 13C NMR (125 MHz, CDCl3): 138.53, 138.35, 128.29, 127.74,
127.54, 114.75, 109.49, 78.40, 77.55, 72.83, 65.85, 36.20, 34.85,
30.60, 29.20, 25.15, 24.00, 23.82; MS–ESIMS: m/z 339 (M+Na)+;
½
a 2D7:2
ꢃ
¼ ꢀ0:4 (c 0.102, CHCl3); IR (neat):
c
max: 3456, 2930, 2860,
;
1640, 1455, 1070, 911, 770, 738, 697 cmꢀ1
1H NMR (300 MHz,
CDCl3): 7.35 (m, 5H), 5.81 (m, 1H), 4.99 (t, J = 11.33 Hz, 2H), 4.62
(d, J = 11.33 Hz, 1H), 4.52 (d, J = 11.33 Hz, 1H), 3.85 (br s, 1H),
3.38 (m, 1H), 2.26 (m, 1H), 2.08 (m, 2H), 1.72 (m, 1H), 1.58–1.26
(m, 8H), 0.9 (t, J = 6.04 Hz, 3H); 13C NMR (125 MHz, CDCl3):
138.47, 138.33, 128.35, 127.77, 127.65, 114.71, 81.45, 71.77,
71.48, 32.0, 31.84, 29.84, 27.71, 25.82, 22.54, 13.98; MS–ESIMS:
m/z 299 (M+Na)+; HR ESIMS: m/z calcd for C18H28O2Na:
299.19815; found: 299.19859.
HR ESIMS: m/z calcd for
C20H28O3Na: 339.19307; found:
339.19226.
4.1.9. (2R,3S)-3-(Benzyloxy)hept-6-ene-1,2-diol 19
To a stirred solution of the compound 18 (1.8 g, 5.70 mmol) in
THF/H2O (9:1; 30 mL), trifluoroacetic acid (0.652 mL, 8.51 mmol)
was added slowly at 0 °C and stirred for an additional 6 h at room
temperature. After completion of the reaction, it was quenched
with an aqueous sodium bicarbonate solution. Next, the THF was
evaporated, extracted with EtOAc (2 ꢂ 25 mL), dried over anhy-
drous Na2SO4, and concentrated in vacuo. The residue was purified
by column chromatography (silica gel, 60–120 mesh, EtOAc/hex-
4.1.12. (2R,3R)-((5S,6R)-5-(Benzyloxy)undec-1-en-6-yl) 3-(4-
methoxybenzyloxy)-2-methylpent-4-enoate 22
To a stirred solution of compound 21 (0.18 g, 0.65 mmol) in dry
CH2Cl2 (15 mL), DCC (0.268 g, 1.30 mmol), acid 14 (0.195 mg,
0.78 mmol), and DMAP (catalytic amount) were added at 0 °C
and stirred at room temperature for 3 h. After completion of the
reaction, the reaction mixture was filtered through Celite and ex-
tracted with CH2Cl2 (2 ꢂ 20 ml), dried over anhydrous Na2SO4,
and concentrated under reduced pressure. The residue was puri-
fied by column chromatography (silica gel, 60–120 mesh, EtOAc–
ane 45:55) to afford 19 (1.07 g, 80%) as
¼ ꢀ66:3 (c 0.149, CHCl3); IR (neat): max: 3411, 2927, 2875,
1452, 1090, 911, 740, 698 cmꢀ1 1H NMR (300 MHz, CDCl3): 7.34
a colorless syrup.
½
a 2D6:9
ꢃ
c
;
(m, 5H), 5.81 (m, 1H), 5.00 (dt, J = 28.70, 18.88, 1.511 Hz, 2H), 4.6
(q, J = 15.108, 11.33 Hz, 2H), 3.74 (m, 3H), 3.58 (qn, J = 8.30, 4.53
Hz, 1H), 2.39 (br s, 1H), 2.17 (m, 2H), 1.77 (m, 2H); 13C NMR
(125 MHz, CDCl3): 138.09, 138.02, 128.43, 127.81, 114.99, 80.19,
72.57, 63.31, 29.54, 29.40; MS–ESIMS: m/z 259 (M+Na)+; HR
ESIMS: m/z calcd for C14H20O3Na: 259.13047; found: 259.13012.
hexane 4:96) to afford 22 (0.27 g, 82%) as a liquid. ½a D27:2
¼ ꢀ11:7
ꢃ
(c 0.066, CHCl3); IR (neat): cmax: 2930, 2860, 1731, 1513, 1458,
1248, 1180, 1072, 1035 cmꢀ1 1H NMR (300 MHz, CDCl3): 7.28
;
(m, 5H), 7.19 (d, J = 9.05 Hz, 2H), 6.79 (d, J = 9.05 Hz, 2H), 5.71
(m, 2H), 5.32 (m, 2H), 4.99 (m, 3H), 4.64 (d, J = 11.33 Hz, 1H),
4.47 (d, J = 10.57, Hz, 1H), 4.26 (d, J = 11.33 Hz, 2H), 3.96 (t,
J = 8.30 Hz, 1H), 3.76 (s, 3H), 3.46 (m, 1H), 2.65 (m, 1H), 2.22 (m,
1H), 2.06 (m, 1H), 1.58 (m, 4H), 1.25 (m, 6H), 1.09 (d, J = 6.79 Hz,
3H), 0.84 (t, J = 6.79 Hz, 3H); 13C NMR (125 MHz, CDCl3): 174.66,
158.92, 138.76, 138.32, 135.91, 130.38, 129.28, 128.14, 127.81,
127.33, 119.86, 114.78, 113.51, 82.69, 80.01, 75.52, 72.58, 70.14,
55.12, 45.04, 31.61, 30.34, 30.02, 28.99, 25.35, 22.45, 13.95,
13.73; MS–ESIMS: m/z 531 (M+Na)+; HR ESIMS: m/z calcd for
4.1.10. (R)-2-((S)-1-(Benzyloxy)pent-4-enyl)oxirane 20
To a stirred solution of diol 19 (1 g, 4.23 mmol) in dry CH2Cl2
(25 mL) were added Bu2SnO (catalytic), p-TsCl (0.805 g,
4.22 mmol), and Et3N (0.707 mL, 5.08 mmol) at 0 °C and allowed
to stir at room temperature for 5 h. Next, the reaction mixture
was extracted with CH2Cl2 (2 ꢂ 25 mL), dried over anhydrous
Na2SO4, and concentrated in vacuo to afford a mono tosylated
product. This was used as the starting material for the next step.
To a stirred solution of this mono tosylated compound taken in
dry methanol (20 mL), was added solid K2CO3 (1.16 g, 8.40 mmol)
at 0 °C and stirred at the same temperature for 1 h. After comple-
tion of the reaction, K2CO3 was filtered through a Celite pad. Meth-
anol was evaporated and extracted with CHCl3 (2 ꢂ 20 mL). The
combined organic phases were dried over anhydrous Na2SO4 and
concentrated in vacuo. The residue was purified by column chro-
matography (silica gel, 60–120 mesh, EtOAc/hexane 5:95) to afford
the compound 20 (0.73 g, 79%, over two steps) as a liquid.
C32H44O5Na: 531.30810; found: 531.30643.
4.1.13. (3R,4R,9S,10R,Z)-9-(Benzyloxy)-4-(4-methoxybenzyl-
oxy)-3-methyl-10-pentyl-3,4,7,8,9,10-hexahydro-2H-oxecin-2-one
23
A second generation Grubbs’ catalyst (0.034 g, 0.04 mmol) was
added to a solution of diene ester 22 (0.2 g, 0.39 mmol) in degassed
anhydrous toluene (1000 mL) and the mixture was heated under
an Ar flow for 8 h. After completion of the reaction, most of the sol-
vent was evaporated and then air was bubbled in order to favor
catalyst decomposition. The remaining solvent was evaporated un-
der reduced pressure, to afford a dark brown oily residue, which
was purified by column chromatography (silica gel, 60–120 mesh,
EtOAc–hexane 5:95) to afford 23 (0.122 g, 65%) as a liquid.
½
a 2D7:2
ꢃ
¼ ꢀ16:7 (c 0.108, CHCl3); IR (neat):
cmax: 2921, 1640, 1454,
1070 cmꢀ1 1H NMR (300 MHz, CDCl3): 7.34 (m, 5H), 5.80 (m,
;
1H), 5.02 (ddd, J = 17.0, 3.4, 1.7 Hz, 1 H,), 4.96 (ddd, J = 10.2, 3.4,
1.7 Hz, 1 H), 4.67 (d, J = 11.33 Hz, 1H), 4.49 (d, J = 11.33 Hz, 1H),
3.29 (q, J = 12.84, 6.04 Hz, 1H), 2.95 (m, 1H), 2.8 (t, J = 3.77 Hz,
1H), 2.73 (m, 1H), 2.28 (m, 1H), 2.18 (m, 1H), 1.75 (m, 2H); 13C
NMR (75 MHz, CDCl3): d = 138.5, 138.2, 128.4, 127.8, 127.7,
115.0, 77.5, 72.4, 53.5, 45.7, 32.1, 29.4; MS–ESIMS: m/z 241
(M+Na)+; HR ESIMS: m/z calcd for C14H19O2: 219.13850; found:
219.13749.
½
a 2D7:2
ꢃ
¼ þ101:1 (c 0.043, CHCl3); IR (neat):
cmax: 2932, 2862,
1738, 1513, 1458, 1246, 1190, 1076, 1034, 738 cmꢀ1
;
1H NMR
(500 MHz, CDCl3): 7.30 (m, 5H), 7.25 (d, J = 8.54, 2H), 6.88 (d,
J = 8.545 Hz, 2H), 5.76 (dt, J = 11.74 Hz, 4.12, 1H), 5.37 (t,
J = 10.52 Hz, 1H), 5.14 (m, 1H), 4.87 (br s, 1H), 4.51 (m, 3H), 4.33