6574
C. J. Sinz, S. D. Rychnovsky / Tetrahedron 58 (2002) 6561–6576
1
44 (6.8 mg, 0.008 mmol, 75%) in addition to benzyl ether
45 (2.6 mg, 0.003 mmol, 25%), both as colorless oils.
Analytical data for the desired diol 44: 1H NMR (500 MHz,
C6D6) d 5.66 (dd, J¼15.6, 7.6 Hz, 1H), 5.55 (d, J¼15.6,
5.6 Hz, 1H), 4.33 (ddd, J¼9.0, 3.6, 3.6 Hz, 1H), 4.28–4.21
(m, 2H), 4.18–4.13 (m, 2H), 4.06–3.96 (m, 2H), 3.71 (t,
J¼5.8 Hz, 2H), 3.54–3.50 (m, 1H), 2.99 (t, J¼5.8 Hz, 1H),
2.28–2.24 (m, 1H), 2.07–2.00 (m, 2H), 1.90–1.84 (m, 1H),
1.68–1.53 (m, 1H), 1.54 (s, 3H), 1.46 (s, 3H), 1.45 (s, 3H),
1.44 (s, 3H), 1.44–1.36 (m, 6H), 1.42 (s, 3H), 1.41 (s, 3H),
1.34 (s, 3H), 1.27 (s, 3H), 1.22–1.10 (m, 6H), 1.00 (s, 9H),
0.99 (d, J¼6.7 Hz, 3H), 0.92 (d, J¼6.6 Hz, 3H), 0.84 (d,
J¼6.1 Hz, 3H), 0.79 (d, J¼6.9 Hz, 3H) 0.15 (s, 3H), 0.14 (s,
3H); 13C NMR (125 MHz, C6D6) d 134.4, 131.4, 100.5 (2),
98.7, 98.5, 79.8, 70.9, 70.5, 70.2, 70.0, 66.2, 66.0, 63.5,
63.4, 63.3, 60.8, 45.2, 43.3, 43.1, 40.4 (2), 39.5 (2), 37.9,
36.5, 35.6, 31.3 (2), 31.0, 30.8, 26.5 (2), 25.7, 25.4, 20.3,
20.2, 20.1, 18.7, 17.4, 15.3, 9.8, 23.8, 24.0; IR (NaCl, film)
3446, 3053, 1645, 1385, 1265 cm21; HRMS (electrospray)
calcd for C46H86O11SiNa 865.5837, found 865.5859
[MþNa]þ; [a]D¼1.8 (c 0.90, CH2Cl2).
of the 1H NMR spectrum revealed an E/Z ratio of 11:1: H
NMR (500 MHz, C6D6) d 6.60 (dt, J¼14.4, 7.3 Hz, 1H),
5.90 (d, J¼14.4 Hz, 1H), 5.67 (dd, J¼15.6, 7.7 Hz, 1H),
5.56 (dd, J¼15.6, 5.6 Hz, 1H), 4.26–4.22 (m, 3H), 4.19–
4.14 (m, 3H), 4.07–3.97 (m, 2H), 3.52–3.47 (m, 1H), 2.98
(t, J¼5.6 Hz, 1H), 2.25 (ddd, J¼13.5, 13.5, 6.7 Hz, 1H),
2.09–1.93 (m, 5H), 1.83–1.78 (m, 2H), 1.73–1.67 (m, 2H),
1.65–1.56 (m, 3H), 1.55 (s, 3H), 1.47 (s, 3H), 1.46 (s, 3H),
1.44 (s, 3H), 1.43 (s, 3H), 1.42–1.36 (m, 3H), 1.40 (s, 3H),
1.34 (s, 3H), 1.25 (s, 3H), 1.03 (d, J¼6.7 Hz, 3H), 1.00 (s,
9H), 0.92 (d, J¼6.7 Hz, 3H), 0.90–0.83 (m, 3H), 0.79 (d,
J¼6.9 Hz, 3H), 0.77 (d, J¼7.1 Hz, 3H), 0.10 (s, 3H), 0.09
(s, 3H); 13C NMR (125 MHz, C6D6) d 144.7, 134.3, 131.5,
128.5, 100.5 (2), 98.7, 98.4, 79.7, 76.6, 71.3, 70.8, 70.2,
66.2, 66.0, 63.5, 63.3, 63.2, 45.1, 43.3 (2), 43.2, 40.4 (2),
40.0, 39.5 (2), 39.3, 38.0, 35.4, 31.3, 31.0, 30.8, 26.5, 25.7,
25.5, 20.3, 20.2, 20.1, 18.7, 17.3, 15.3, 10.0, 23.7, 24.0; IR
(NaCl, film) 3430, 3054, 2987, 1422, 1264 cm21; HRMS
(electrospray) calcd for C47H85IO10SiNa 987.4855, found
987.4830 [MþNa]þ; [a]D¼þ6.9 (c 1.0, CH2Cl2).
5.1.24. Phosphonate ester (48). To a solution of 47
(20.0 mg, 0.021 mmol) in CH2Cl2 (600 mL) was added
DMAP (46 mg, 0.38 mmol) followed by BOP reagent
(128 mg, 0.29 mmol). To this mixture was added (diethyl-
phosphono)acetic acid (57.0 mg, 0.29 mmol) as a solution
in CH2Cl2 (500 mL). The resulting mixture was stirred at
room temperature for 48 h, at which point it was diluted
with EtOAc. The organic phase was washed with sat. aq.
NaHCO3 and brine, then dried over Na2SO4 and concen-
trated. Purification by flash chromatography (50% EtOAc/
hexanes) provided phosphonate ester 49 (25.0 mg,
0.021 mmol, ,100%) as a colorless oil: 1H NMR
(500 MHz, CDCl3) d 6.51 (ddd, J¼14.4, 7.5, 7.5 Hz, 1H),
5.97 (d, J¼14.4 Hz, 1H), 5.54–5.46 (m, 2H), 4.71 (dd,
J¼7.5, 4.8 Hz, 1H), 4.31–4.27 (m, 1H), 4.20–4.14 (m, 2H),
3.94–3.91 (m, 9H), 3.71–3.61 (m, 1H), 2.97 (d, J¼21.6 Hz,
2H), 2.49–2.44 (m, 1H), 2.28–2.01 (m, 3H), 1.89–1.80 (m,
4H), 1.72–1.70 (m, 1H), 1.58–1.45 (m, 17H), 1.43 (s, 3H),
1.39 (s, 3H), 1.38 (s, 3H), 1.36 (s, 3H), 1.34 (s, 6H), 1.33 (s,
6H), 1.00 (d, J¼6.7 Hz, 3H), 0.89 (d, J¼7.7 Hz, 6H), 0.88
(s, 9H), 0.80 (d, J¼7.0 Hz, 3H), 0.04 (s, 3H), 0.02 (s, 3H);
13C NMR (125 MHz, CDCl3) d 165.6 (d, J3-P¼6.2 Hz),
144.3, 139.2, 133.3, 131.6, 100.3 (2), 98.5, 98.1, 82.2, 76.0,
70.9, 70.0 (2), 65.7, 65.3, 63.0, 62.9, 62.7, 62.5
(J3-P¼6.2 Hz), 62.5 (J3-P¼6.2 Hz), 43.9, 42.3, 42.2, 42.1,
39.0, 38.7 (2), 38.5, 36.8, 34.3, 34.2 (J2-P¼134 Hz), 30.2,
30.1, 29.6, 25.8, 24.9 (2), 24.8 (2), 19.8, 19.7, 19.6, 18.0,
16.3 (J4-P¼6.2 Hz), 16.3 (J4-P¼6.2 Hz), 16.2, 15.7, 9.6,
24.3, 24.7; IR (NaCl, film) 3054, 1727, 1632, 1422,
1381 cm21; [a ]D¼þ9.3 (c 0.40, CH2Cl2).
5.1.22. Aldehyde (46). To a solution of alcohol 44
(12.0 mg, 14.2 mmol) in CH2Cl2 (1 mL) was added freshly
prepared pH 8.6 buffer (1 mL; 0.5 M NaHCO3/0.05 M
Na2CO3). N-Chlorosuccinimide (ca. 1 mg), TEMPO (one
crystal), and Bu4NCl (ca. 1 mg) were added sequentially.
The resulting mixture was stirred vigorously at room
temperature. After 2 h, the reaction mixture was diluted
with CH2Cl2, dried over Na2SO4, and concentrated.
Purification by flash chromatography (15% EtOAc/hexanes
then 30% EtOAc/hexanes) provided aldehyde 46 (10.5 mg,
12.5 mmol, 88%) as a colorless oil. This unstable aldehyde
was immediately taken forward: 1H NMR (500 MHz, C6D6)
d 9.70 (dd, J¼3.0, 1.6 Hz, 1H), 5.68 (dd, J¼15.7, 7.7 Hz,
1H), 5.57 (dd, J¼15.7, 5.4 Hz, 1H), 4.67 (app dt, J¼8.5,
3.8 Hz, 1H), 4.29–4.13 (m, 7H), 3.39–3.35 (m, 1H), 2.98 (t,
J¼5.8 Hz, 1H), 2.35 (ddd, J¼15.6, 8.5, 3.0 Hz, 1H), 2.25
(dd, J¼13.6, 6.7 Hz, 1H), 2.20 (ddd, J¼15.6, 3.7, 1.6 Hz,
1H), 1.86–1.82 (m, 1H), 1.72–1.62 (m, 4H), 1.65 (s, 3H),
1.59–1.52 (m, 5H), 1.55 (s, 3H), 1.46 (s, 3H), 1.44 (s, 3H),
1.41 (s, 3H), 1.39–1.33 (m, 6H), 1.34 (s, 3H), 1.22 (s, 3H),
1.04 (d, J¼6.7 Hz, 3H), 0.96 (s, 9H), 0.92 (d, J¼6.6 Hz,
3H), 0.79 (d, J¼6.8 Hz, 3H), 0.76 (d, J¼7.0 Hz, 3H), 0.11
(s, 3H), 0.08 (s, 3H).
5.1.23. Vinyl iodide (47). Chromous chloride (57.0 mg,
0.46 mmol) was suspended in THF (300 mL), which had
been degassed by an argon sparge. In a separate flask,
aldehyde 46 (28.0 mg, 0.033 mmol) was dissolved in
dioxane (1.8 mL), and to this solution was added iodoform
(113 mg, 0.29 mmol). Both flasks were then briefly
degassed by an argon sparge. The aldehyde/iodoform
solution was added to the suspension of chromous chloride
via cannula, and the resulting mixture was stirred at room
temperature in the absence of light. After 3.5 h, the reaction
was quenched by the addition of sat. aq. NH4Cl, diluted with
H2O, and extracted twice with EtOAc. The combined
organic phases were washed successively with sat. aq. NaCl,
0.5 M aq. Na2S2O3, again with sat. aq. NaCl, then dried over
MgSO4. Purification by flash chromatography (5% EtOAc/
hexanes then 30% EtOAc/hexanes) provided vinyl iodide 47
(28.0 mg, 0.29 mmol, 88%) as an amorphous solid. Analysis
5.1.25. 9-Tributylstannyl-nona-2,4,6,8-tetraen-1-ol (4).
To a cooled (2788C) solution of ester 4940 (130 mg,
0.278 mmol) in THF (3 mL) was added DIBAL-H
(1.11 mL, 1.0 M in toluene, 1.11 mmol) dropwise. After
90 min, the reaction was quenched by dropwise addition of
MeOH (750 mL), then was diluted with Et2O and Rochelle’s
salt, and stirred rapidly at room temperature. The layers
were separated, and the organic phase was diluted with
hexanes and dried over Na2SO4. Purification by flash
chromatography (5% EtOAc/hexanes with 2% Et3N, then
15% EtOAc/hexanes with 2% Et3N) afforded 4 (63 mg,