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E,Z 90:10, R,S/R,R > 95:5) in toluene (34 mL) at −78 °C was added
DIBAL-H (1 M in heptane, 2.02 mL, 2.02 mmol) dropwise. After 5 h,
MeOH (4 mL) was slowly added to quench remaining DIBAL-H, and
the reaction mixture was allowed to warm to room temperature. After
1 h, the reaction mixture was washed with aq tartaric acid (0.5 M, 130
mL) and extracted with Et2O (3 × 50 mL). The organic phase was
washed with brine (20 mL) and dried over anhydrous Na2SO4.
Concentration afforded the crude aldehyde 17b (0.921 g, quantitative
yield) as a pale yellow oil: 1H NMR (300 MHz, CDCl3) δ 9.54 (d, J =
1.5 Hz, 1H), 7.66−7.61 (m, 4H), 7.47−7.34 (m, 6H), 7.26 (d, J = 8.6
Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 5.71−5.41 (m, 4H), 4.41 (s, 2H),
4.09−4.00 (m, 2H), 3.93 (m, apparent d, J = 5.0 Hz, 2H), 3.80 (s,
3H), 2.39−2.35 (m, 2H), 2.27−2.14 (m, 2H), 1.11 (s, 9H), 0.88 (s,
9H), 0.02 (s, 3H), 0.01 (s, 3H). This material was stored frozen in
benzene (ca. −5 °C) and used in the subsequent step without further
purification.
7.45−7.33 (m, 6H), 5.78 (ddd, J = 16.8, 10.4, 6.1 Hz, 1H), 5.64−5.62
(m, 2H), 5.46 (ddd, J = 14.8, 6.8, 6.8 Hz, 1H), 5.31 (dd, J = 15.4, 6.2
Hz, 1H), 5.04−4.97 (m, 2H), 4.17 (ddd, apparent q, J = 5.9 Hz, 1H),
4.08−4.05 (m, 2H), 4.03 (ddd, apparent q, J = 6.2 Hz, 1H), 2.23−
2.13 (m, 4H), 1.20−1.40 (br s, 1H), 1.08 (s, 9H), 0.87 (s, 9H), 0.01
(s, 3H), −0.01 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.3,
136.09, 136.05, 135.7, 134.5, 134.2, 131.3, 129.75, 129.66, 129.6,
127.6, 127.5, 125.7, 114.7, 74.4, 73.2, 63.9, 41.5, 40.7, 27.2, 26.0, 19.5,
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18.4, −4.1, −4.6. For (R,E,S,Z)-39: H NMR (400 MHz, CDCl3) δ
4.11 (apparent d, J = 6.1 Hz, 2H), other peaks were not resolved.
(2E,5S,6E,9R)-Methyl 5-((tert-Butyldimethylsilyl)oxy)-9-((tert-
butyldiphenylsilyl)oxy)undeca-2,6,10-trienoate (19a). To a solution
of alcohol 39 (58.4 mg, 0.106 mmol, E,E/E,Z 89:11) in petroleum
ether (5.3 mL) was added activated MnO2 (184.0 mg, 2.120 mmol).
After 19 h, the petroleum ether was removed by rotary evaporation,
and another portion of activated MnO2 (184.0 mg, 2.120 mmol) was
added along with KCN (36.6 mg, 0.562 mmol), acetic acid (glacial,
9.8 μL, 0.170 mmol), and MeOH (5.3 mL). [CAUTION: Acidified
reaction mixtures and extraction fractions should be handled in a
fume hood]. After 25 h, the reaction mixture was filtered through
Celite. Concentration and radial chromatography (CH2Cl2) afforded
19a (48.9 mg, 80% yield, E,E/E,Z 94:6, R,S/R,R > 95:5) as a colorless
oil. The isomers could be enriched by careful radial chromatography
(CH2Cl2) with the minor (E,Z)-isomer eluting before the major
To a solution of 5-(methylsulfonyl)-1-phenyl-1H-tetrazole (MeS-
O2PT)47 (0.614 g, 2.74 mmol) in THF (61 mL) at −78 °C was
slowly added KHMDS (0.5 M in toluene, 5.20 mL, 2.60 mmol). After
1 h, aldehyde 17b (0.921 g, 1.37 mmol) in THF (7 mL) was slowly
added. After 5 h, the reaction was quenched with saturated aq NH4Cl
(10 mL) and H2O (10 mL), allowed to warm to room temperature
over 30 min, and extracted with EtOAc (3 × 30 mL). The organic
phase was washed with brine (20 mL) and dried over anhydrous
Na2SO4. Concentration and gradient flash chromatography (petro-
leum ether to Et2O) afforded 18 (0.750 g, 83% yield over two steps
E,E/E,Z 90:10, R,S/R,R > 95:5) as a colorless oil. The E,E/E,Z
isomers and R,S/R,R diastereomers were inseparable by radial/flash
chromatography and their ratios were determined by 1H NMR:
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(E,E)-isomer, and their ratios were determined by H NMR: [α]D
−33.3 (c 1.27, CHCl3); IR (film) 3072, 2955, 2931, 2895, 2857, 1727,
1653, 1462, 1427, 1258, 1168, 1112, 1072 cm−1; HRMS (ESI-TOF)
m/z [M + Na]+ calcd for C34H50O4Si2Na 601.3145, found 601.3148.
Anal. Calcd for C34H50O4Si2: C, 70.54; H, 8.71. Found: C, 70.54; H,
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8.81. For (R,E,S,E)-19a: H NMR (400 MHz, CDCl3) δ 7.70−7.64
[α]D −23.0 (c 1.35, CHCl3); IR (film) 3072, 3048, 2999, 2931,
(m, 4H), 7.45−7.33 (m, 6H), 6.90 (ddd, J = 15.7, 7.4, 7.4 Hz, 1H),
5.80 (d, J = 15.6 Hz, 1H), 5.77 (ddd, J = 16.8, 10.4, 6.1 Hz, 1H), 5.49
(ddd, J = 15.2, 7.2, 7.2 Hz, 1H), 5.30 (dd, J = 15.4, 6.3 Hz, 1H), 5.02
(ddd, apparent dt, J = 17.3, 1.4 Hz, 1H), 4.98 (ddd, apparent dt, J =
10.4, 1.3 Hz, 1H), 4.17 (ddd, apparent q, J = 5.9 Hz, 1H), 4.11 (ddd,
apparent q, J = 6.1 Hz, 1H), 3.72 (s, 3H), 2.37−2.24 (m, 2H), 2.24−
2.12 (m, 2H), 1.07 (s, 9H), 0.87 (s, 9H), 0.01 (s, 3H), −0.02 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 167.0, 146.1, 140.2, 136.1,
136.0, 135.1, 134.5, 134.2, 129.8, 129.7, 127.7, 127.5, 126.4, 123.0,
114.8, 74.4, 72.4, 51.5, 41.5, 40.7, 27.2, 26.0, 19.5, 18.3, −4.2, −4.7.
2895, 2856, 1613, 1513, 1472, 1427, 1361, 1302, 1248, 1173, 1112
cm−1; HRMS (ES-TOF) m/z [M + Na]+ calcd for C41H58O4Si2Na
693.3771, found 693.3781. Anal. Calcd for C41H58O4Si2: C, 73.38; H,
1
8.71. Found: C, 73.66; H, 8.91. For (R,E,S,E)-18: H NMR (400
MHz, CDCl3) δ 7.70 (d, J = 7.2 Hz, 2H), 7.66 (d, J = 7.2 Hz, 2H),
7.44−7.40 (m, 2H), 7.39−7.34 (m, 4H), 7.27 (d, J = 8.4 Hz, 2H),
6.88 (d, J = 8.4 Hz, 2H), 5.78 (ddd, J = 16.8, 10.4, 6.0 Hz, 1H), 5.70−
5.55 (m, 2H), 5.47 (ddd, J = 15.2, 7.2, 7.2 Hz, 1H), 5.33 (dd, J = 15.3,
6.2 Hz, 1H), 5.04−4.96 (m, 2H), 4.42 (s, 2H), 4.18 (ddd, apparent q,
J = 5.9 Hz, 1H), 4.04 (ddd, apparent q, J = 6.0 Hz, 1H), 3.94 (m,
apparent d, J = 5.3 Hz, 2H), 3.81 (s, 3H), 2.26−2.14 (m, 4H), 1.08 (s,
9H), 0.88 (s, 9H), 0.02 (s, 3H), −0.01 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 159.3, 140.3, 136.1, 136.0, 135.7, 134.5, 134.2, 131.0,
130.7, 129.7, 129.6, 129.5, 128.8, 127.6, 127.5, 125.6, 114.7, 113.9,
74.4, 73.2, 71.6, 70.7, 55.4, 41.7, 40.8, 27.2, 26.0, 19.5, 18.4, −4.2,
−4.6.
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For (R,E,S,Z)-19a: H NMR (300 MHz, CDCl3) δ 6.28 (ddd, J =
11.6, 7.1, 7.1 Hz, 1H), 2.81 (ddd, J = 7.2, 5.7, 1.5 Hz, 2H), other
peaks were not resolved.
(2E,5S,6E,9R)-Methyl 9-((tert-Butyldiphenylsilyl)oxy)-5-hydrox-
yundeca-2,6,10-trienoate (19b). To a solution of silyl ether 19a
(0.444 g, 0.767 mmol, E,E/E,Z 97:3) in THF (7.7 mL) was added
HCl (2 M, 2.57 mL, 5.14 mmol). After 46 h, the reaction mixture was
partitioned between saturated aq NaHCO3 (25 mL) and EtOAc (3 ×
25 mL). The organic phase was washed with brine (5 mL) and dried
over anhydrous Na2SO4. Concentration and flash chromatography
(CH2Cl2/MeOH) afforded 19b (0.341 g, 96% yield, E,E/E,Z 95:5) as
a pale yellow oil. The isomers could be enriched by careful radial
chromatography (5% MeOH in CH2Cl2) with the minor (E,Z)-
isomer eluting before the major (E,E)-isomer, and their ratios were
(2E,5S,6E,9R)-5-((tert-Butyldimethylsilyl)oxy)-9-((tert-
butyldiphenylsilyl)oxy)undeca-2,6,10-trien-1-ol (38). To a solution
of benzyl ether 18 (54.0 mg, 0.080 mmol, E,E/E,Z 90:10, R,S/R,R >
95:5) in CH2Cl2 (2.6 mL) and H2O (0.14 mL) was added DDQ
(27.0 mg, 0.120 mmol) with vigorous stirring. After 1.5 h, the reaction
mixture was filtered through Celite. The filtrate was washed with
saturated aq NaHCO3 (10 mL) and brine (20 mL) and extracted with
CH2Cl2 (3 × 10 mL). The organic phase was then washed with brine
(5 mL) and dried over anhydrous Na2SO4. Concentration and radial
chromatography (5% MeOH in CH2Cl2) afforded the corresponding
primary alcohol 39 (38.4 mg, 87% yield, E,E/E,Z 90:10) as a pale
yellow oil. The isomers could be enriched by careful radial
chromatography (CH2Cl2/MeOH) with the minor (E,Z)-isomer
eluting before the major (E,E)-isomer, and their ratios were
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determined by H NMR: [α]D −36.9 (c 0.870, CHCl3); IR (film)
3436, 3072, 3049, 3013, 2998, 2932, 2895, 2858, 1726, 1710, 1659,
1472, 1428, 1320, 1277, 1210, 1169, 1112 cm−1; HRMS (ESI-TOF)
m/z [M + Na]+ calcd for C28H36O4SiNa 487.2281, found 487.2294.
Anal. Calcd for C28H36O4Si: C, 72.37; H, 7.81. Found: C, 72.55; H,
1
7.97. For (R,E,S,E)-19b: H NMR (400 MHz, CDCl3) δ 7.70−7.68
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determined by H NMR: [α]D −28.8 (c 1.50, CHCl3); IR (film)
3345, 3072, 3049, 2999, 2930, 2894, 2857, 1590, 1472, 1427, 1389,
1362, 1256, 1112, 1006 cm−1; HRMS (ESI-TOF) m/z [M + Na]+
calcd for C33H50O3Si2Na 573.3196, found 573.3200. Anal. Calcd for
C33H50O3Si2: C, 71.94; H, 9.15. Found: C, 71.95; H, 9.28. For
(m, 2H), 7.65−7.63 (m, 2H), 7.45−7.33 (m, 6H), 6.91 (ddd, J =
15.7, 7.4, 7.4 Hz, 1H), 5.87 (ddd, J = 15.8, 1.4, 1.4 Hz, 1H), 5.80
(ddd, J = 16.8, 10.4, 6.1 Hz, 1H), 5.52 (ddd, J = 14.4, 7.2, 6.8 Hz,
1H), 5.34 (dd, J = 15.4, 6.8 Hz, 1H), 5.06 (ddd, J = 17.2, 1.4, 1.4 Hz,
1H), 5.02 (ddd, J = 10.4, 1.4, 1.4 Hz, 1H), 4.21 (ddd, apparent q, J =
5.8 Hz, 1H), 4.09 (ddd, apparent q, J = 6.3 Hz, 1H), 3.72 (s, 3H),
1
(R,E,S,E)-39: H NMR (400 MHz, CDCl3) δ 7.71−7.65 (m, 4H),
M
J. Org. Chem. XXXX, XXX, XXX−XXX