21
ACCEPTED MANUSCRIPT
J = 7.9 Hz, 9H), 0.90 (s, 9H), 0.88 (s, 9H), 0.60 (q, J = 7.9 Hz, 6H), 0.15 (s, 3H), 0.12 (s, 3H),
13
0.05 (s, 6H); C NMR (100 MHz, CDCl3): δ 86.0, 72.6, 66.6, 65.8, 59.6, 47.7, 46.7, 25.91
(3C), 25.87 (3C), 23.8, 18.2, 18.0, 6.9 (3C), 5.3 (3C), -4.3 (2C), -4.6, -4.7; MS (EI, 70 eV)
m/z (abundance): 501 (M+•, 1), 243 (17), 233 (38), 189 (28), 169 (30), 161 (16), 160 (11), 159
(77), 147 (13), 133 (16), 115 (32), 113 (21), 105 (14), 103 (29), 87 (16), 75 (25), 73 (100), 59
(17); HRMS: calculated for C26H56O3NaSi3 (M+Na+): 523.3430. Found: 523.3411.
4.10.3. (3S,5R,7R)-3,7-bis(tert-Butyldimethylsilyloxy)-5-hydroxyoct-1-yne (17): To a
solution of silyl ether 15’” (400 mg, 0.798 mmol, 1 equiv) in EtOH (8 mL) at rt was added
PPTS (20 mg, 79.8 µmol, 10 mol %) and the mixture was stirred at rt for 3 h. The reaction
mixture was quenched with a saturated aqueous solution of NaHCO3 (10 mL), stirred for 1 h
and the aqueous phase was extracted with Et2O (3 × 30 mL). The combined organic phases
were washed with a saturated aqueous solution of NaHCO3 (30 mL), H2O (20 mL) and brine
(20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude
material was purified by flash chromatography on silica gel (petroleum ether/EtOAc = 95:5)
to afford alcohol 17 (280 mg, 0.724 mmol, 91%, dr > 98:2) as a white solid. m.p. = 71 °C;
[ꢀ]ꢂꢁꢃ –55.4 (c 0.28, CHCl3); IR (neat): 3293, 2954, 2930, 2858, 2115, 1462, 1377, 1254,
1
1088, 1005, 942 cm-1; H NMR (400 MHz, CDCl3): δ 4.66 (td, J = 6.0 and J = 2.0 Hz, 1H),
4.13-4.00 (m, 2H), 3.63 (br s, 1H, OH), 2.38 (d, J = 2.0 Hz, 1H), 1.77 (tapp, J = 6.0 Hz, 2H),
1.62 (dtapp, J = 14.2 and J = 8.9 Hz, 1H), 1.51 (ddd, J = 14.1, J = 4.3 and J = 2.8 Hz, 1H), 1.18
13
(d, J = 6.1 Hz, 3H), 0.91 (s, 9H), 0.89 (s, 9H), 0.16 (s, 3H), 0.14 (s, 3H), 0.10 (s, 6H); C
NMR (100 MHz, CDCl3): δ 85.5, 72.2, 69.3, 67.0, 60.0, 46.2, 45.7, 25.9 (6C), 24.3, 18.2,
17.9, -4.0, -4.7, -4.8, -5.2; MS (EI, 70 eV) m/z (abundance): 386 (M+•, 1), 197 (9), 189 (8),
169 (8), 159 (20), 155 (45), 147 (12), 146 (10), 145 (88), 133 (10), 129 (25), 119 (29), 115
(23), 105 (12), 103 (17), 101 (21), 75 (100), 74 (10), 73 (99), 59 (18); HRMS: calculated for
C20H42O3NaSi2 (M+Na+): 409.2565. Found: 409.2564.
4.11. Synthesis of compound 19
(2R,4R,6S)-2,6-bis(tert-Butyldimethylsilyloxy)oct-7-yn-4-yl
2-(diethoxyphosphoryl)acetate (19): To a solution of alcohol 17 (280 mg, 0.724 mmol, 1.0
equiv), 2-(diethoxyphosphoryl)acetic acid 1816 (213 mg, 1.09 mmol, 1.5 equiv) and DMAP
(40 mg, 0.326 mmol, 0.45 equiv) in CH2Cl2 (36 mL) at rt was added DCC (336 mg, 1.63
mmol, 2.25 equiv) and the mixture was stirred for 24 h. The mixture was concentrated under
reduced pressure and the crude material was purified by flash chromatography on silica gel
(petroleum ether/EtOAc = 80:20 to 60:40) to afford ester 19 (362 mg, 0.641 mmol, 89%, dr >
98:2) as a colorless oil. [ꢀ]ꢂꢁꢃ –17.5 (c 1.35, CHCl3); IR (neat): 3311, 2955, 2930, 2857, 1735,
1463, 1391, 1252, 1100, 1051, 1023 cm-1; 1H NMR (400 MHz, CDCl3): δ 5.14 (m, 1H), 4.39
(ddd, J = 9.1, J = 3.9 and J = 2.1 Hz, 1H), 4.15 (dq, J =8.1 and J = 7.1 Hz, 4H), 3.87 (m, 1H),
2.90 (d, J = 21.6 Hz, 2H), 2.38 (d, J = 2.1 Hz, 1H), 2.08-1.92 (m, 2H), 1.86 (ddd, J = 14.0, J =
6.7 and J = 5.7 Hz, 1H), 1.62 (dtapp, J = 14.0 and J = 6.3 Hz, 1H), 1.33 (td, J = 7.1 and J = 1.2
Hz, 6H), 1.15 (d, J = 6.2 Hz, 3H), 0.87 (s, 9H), 0.86 (s, 9H), 0.12 (s, 3H), 0.07 (s, 3H), 0.04 (s,
13
3H), 0.03 (s, 3H); C NMR (100 MHz, CDCl3): δ 165.0 (d, J = 6.0 Hz), 85.2, 72.5, 70.2,
65.4, 62.6 (d, J = 6.0 Hz, 2C), 59.1, 44.3, 43.8, 34.5 (d, J = 133.8 Hz), 25.9 (3C), 25.7 (3C),