Total Synthesis of (+)-Strictifolione
CHOCH2), 2.23 (t, J = 7.0 Hz, 2 H, PhCH2CH2), 2.69 (ddd, J = 129.33, 129.36, 129.42, 129.48, 130.76, 130.79, 130.86, 134.39,
6.6, 2.3, 2.3 Hz, 2 H, PhCH2), 3.69–3.77 (m, 1 H, CHOCH2Ar),
3.79 (s, 3 H, OCH3), 3.81 (s, 3 H, OCH3), 3.97–4.04 (m, 1 H, CHO-
CH2Ar), 4.36–4.63 (m, 4 H, OCH2Ar), 5.15 (d, J = 15.5 Hz, 1 H,
-CHSn), 5.85 (ddd, J = 16.7, 7.1, 7.1 Hz, 1 H, CH=CHSn), 6.91
(d, J = 8.6 Hz, 4 H, ArH), 7.17–7.31 (m, 9 H, ArH, PhH) ppm.
13C NMR (50 MHz, CDCl3): δ = 13.4, 16.2, 17.3, 26.6, 26.8, 27.6,
30.7, 31.5, 35.0, 35.3, 39.3, 42.0, 54.9, 70.0, 70.3, 75.4, 75.7, 113.7,
114.2, 117.3, 125.6, 128.2, 129.4, 130.2, 131.6, 134.8, 141.8, 158.6,
159.1 ppm. C42H62O4Sn (749.64): calcd. C 67.29, H 8.34; found C
67.34, H 8.25.
134.86, 134.90, 134.94, 142.31, 159.02, 159.11 ppm.
Synthesis of Compound 8 by Chiral Reduction
(E,4R,8S,10S)-8,10-Bis(4-methoxybenzyloxy)-12-phenyldodeca-1,5-
dien-4-ol (8): To a solution of 33 (0.35 g, 0.66 mmol) in EtOAc
(5 mL) in a round-bottomed flask was added IBX (557 mg,
1.99 mmol) in one portion and the reaction mixture was refluxed
for 6 h. The reaction mixture was filtered through a pad of celite
and filtrate was concentrated to give the crude enone product 34,
which was pure enough and used in the next step without further
purification. To a solution of above crude product 34 (349.0 mg,
0.570 mmol) in THF (10 mL) was added (R)-BINAL-H (0.5 m
solution in THF, 7.52 mL, 3.76 mmol) at –78 °C. The reaction mix-
ture was stirred at –78 °C for 3 h. The resultant mixture was treated
with 1.0 n HCl (10 mL) and extracted with CHCl3 (3ϫ20 mL).
The organic layer was washed with 1.0 n NaOH (20 mL), brine
(20 mL), dried (Na2SO4), filtered, and concentrated. Silica gel col-
umn chromatography of the crude product using petroleum ether/
EtOAc (8:2) as eluent gave 8 (210 mg, 75 %) as a colorless oil.
1-{[(E,3S,5S)-5-(4-Methoxybenzyloxy)-8-iodo-1-phenyloct-7-en-3-
yloxy]methyl}-4-methoxybenzene (9): To a cooled (0 °C) and stirred
solution of 32 (1.3 g, 1.73 mmol) in CH2Cl2 (40 mL) was added
iodine (484 mg, 1.91 mmol). After 30 min at 0 °C, the reaction mix-
ture was diluted with CH2Cl2, washed with saturated Na2S2O3 and
10 % KF solutions, and brine. The organic layer was dried
(Na2SO4), filtered, and concentrated. Silica gel column chromatog-
raphy of the crude product using petroleum ether/EtOAc (9.5:0.5)
as eluent gave 9 (0.96 g, 94% yield) as a yellowish oil. [α]2D5 = +6.6
[α]2D5 = +7.9 (c = 1.1, CHCl ). IR (neat): ν
= 3522, 2935, 2857,
˜
3
max
1
(c = 0.7, CHCl ). IR (neat): ν
= 2986, 2937, 2858, 1614, 1511, 1454, 1342, 1104, 1026, 914, 752, 698 cm–1. H NMR (200 MHz,
˜
3
max
1467, 1379, 1171, 1092, 948 cm–1. H NMR (200 MHz, CDCl3): δ
= 1.29–1.39 (m, 2 H, CHOCH2CHO), 1.71 (t, J = 6.2 Hz, 1 H
PhCH2CHA), 1.81–1.93 (m, 1 H, PhCH2CHB), 2.36 (dd, J = 6.8,
5.8 Hz, 2 H, CH2C=CHI), 2.65 (t, J = 8.5 Hz, 2 H, PhCH2), 3.69–
3.77 (m, 1 H CHOCH2Ar), 3.79 (s, 3 H, OCH3), 3.81 (s, 3 H,
CDCl3): δ = 1.69 (t, J = 5.8 Hz, 2 H, CHOCH2CHO), 1.81–1.94
(m, 2 H, PhCH2CH2), 2.05 (br. s, 1 H, OH), 2.23–2.41 (m, 4 H,
CH2CH=CH, CH2CH=CH2), 2.67 (t, J = 7.9 Hz, 2 H, PhCH2),
3.43–3.58 (m, 1 H, CHOH), 3.65–3.70 (m, 2 H, 2XCHOCH2Ar),
3.78 (s, 3 H, OCH3), 3.79 (s, 3 H, OCH3), 4.25 (d, J = 11.1 Hz, 2
1
OCH3), 3.97–4.04 (m, 1 H, CHOCH2Ar), 4.36–4.63 (m, 4 H, H, OCH2Ar), 4.47 (d, J = 8.4 Hz, 2 H, OCH2Ar), 5.10–5.18 (m, 2
OCH2Ar), 6.19 (m, 2 H, CH=CHI), 6.89 (d, J = 8.8 Hz, 4 H, ArH),
7.17–7.31 (m, 9 H, ArH, PhH) ppm. 13C NMR (50 MHz, CDCl3):
δ = 31.3, 35.8, 38.4, 39.7, 55.1, 70.1, 70.4, 75.3, 75.8, 113.7, 114.5,
117.2, 125.8, 128.2, 129.5, 130.2, 131.6, 134.8, 141.8, 158.6, 159.1
ppm. C30H35IO4 (586.51): calcd. C 61.44, H 6.01; found C 61.68,
H 6.22.
H, CH=CH2), 5.51–5.71 (m, 2 H, CH=CH), 5.75–5.92 (m, 1 H,
CH2CH=CH2), 6.88 (d, J = 8.7 Hz, 4 H, ArH), 7.17–7.34 (m, 9 H,
ArH, PhH) ppm. 13C NMR (50 MHz, CDCl3): δ = 31.2, 35.8, 36.8,
39.9, 41.9, 55.2, 70.5, 70.7, 71.7, 74.6, 74.9, 113.8, 118.0, 125.7,
127.4, 128.3, 129.4, 130.8, 134.3, 134.9, 142.3, 159.3, 159.1 ppm.
C34H42O5 (530.70): calcd. C 76.95, H 7.98; found C 77.16, H 7.83.
1-[(3S,5S)-3,5-Bis(4-methoxybenzyloxy)oct-7-enyl]benzene (12): To
a solution of 31 (1.60 g, 3.49 mmol) in ethyl acetate (40 mL) was
added Lindlar’s catalyst (20 mg). The reaction mixture was stirred
for 1 h under a balloon of H2 at room temperature and filtered
through a celite pad. The filtrate was concentrated and the residue
was purified by silica gel column chromatography using petroleum
ether/EtOAc (9:1) as eluent to give 12 (590 mg, 95%) as a pale
(E,8S,10S)-8,10-Bis(4-methoxybenzyloxy)-12-phenyldodeca-1,5-
dien-4-ol (33): To a solution of vinylic iodide 9 (540 mg,
0.927 mmol) in THF (15 mL) was added nBuLi (0.58 mL,
1.0 mmol, 1.6 m solution in hexane) at –78 °C. The yellow mixture
was warmed to 0 °C for 30 min before recooling to –78 °C. Then,
the reaction mixture was treated with CuCN (96 mg, 1.38 mmol),
followed by addition of but-3-enal 10 (78 mg, 0.39 mmol) at –78 °C.
Stirring was continued at –50 °C for 1.5 h. The reaction was
quenched by addition of aqueous NH4Cl, then the aqueous layer
was extracted with EtOAc. The combined organic extracts were
washed with brine, dried (Na2SO4), and concentrated. Silica gel
column chromatography of the crude product using petroleum
ether/EtOAc (8:2) as eluent gave 33 (0.49 g, 68%) as a yellow syr-
yellow oil. [α]2D5 = +16.1 (c = 0.9, CHCl ). IR (neat): ν
= 2938,
˜
3
max
2864, 1949, 1870, 1710, 1641, 1603, 1496, 1454, 1350, 1067 cm–1.
1H NMR (200 MHz, CDCl3): δ = 1.22–1.29 (m, 1 H, CHOCH-
ACHO), 1.34–1.39 (m, 1 H, CHOCHBCHO), 1.71 (t, J = 6.2 Hz, 1
H, PhCH2CHA), 1.81–1.93 (m, 1 H, PhCH2CHB), 2.36 (dd, J =
6.8, 5.8 Hz, 2 H, CH2CH=CH2), 2.67 (t, J = 8.5 Hz, 2 H, PhCH2),
3.61–3.74 (m, 2 H, 2ϫ CHOCH2Ar), 3.78 (s, 3 H, OCH3), 3.81 (s,
3 H, OCH3), 4.25 (dd, J = 10.9, 4.3 Hz, 1 H, OCHAAr), 4.47 (s, 3
H, OCHBAr, OCH2Ar), 5.03–5.15 (m, 2 H, CH=CH2), 5.76–5.93
(m, 1 H, CH=CH2), 6.87 (t, J = 8.8 Hz, 4 H, ArH), 7.17–7.31 (m,
9 H, ArH, PhH) ppm. 13C NMR (50 MHz, CDCl3): δ = 31.1, 35.7,
38.4, 39.8, 55.0, 70.3, 70.5, 74.5, 74.7, 113.6, 114.2, 117.1, 125.6,
128.3, 129.3, 130.3, 130.7, 131.8, 142.2, 158.9, 159.0 ppm.
C30H36O4 (460.61): calcd. C 78.23, H 7.88; found C 78.31, H 7.67.
upy liquid. [α]2D5 = –31.8 (c = 1.1, CHCl ). IR (neat): ν
= 3443,
˜
3
max
3064, 3028, 2938, 2864, 1949, 1870, 1710, 1641, 1603, 1496, 1454,
1350, 1067 cm–1. 1H NMR (200 MHz, CDCl3): (as a diastereomeric
mixture, dr = 2:1): δ = 1.62–1.76 (m, 2 H, CHOCH2CHO), 1.78–
1.94 (m, 2 H, PhCH2CH2), 2.05 (br. s, 1 H, OH), 2.23–2.41 (m, 4
H, CH2CH=CH, CH2CH=CH2), 2.59–2.79 (m, 2 H, PhCH2),
3.41–3.58 (m, 1 H, CHOH), 3.65–3.74 (m, 2 H, 2XCHOCH2Ar),
3.78 (s, 3 H), 3.79 (s, 3 H, OCH3), 3.82 (m, 3 H, OCH3), 4.16 (d,
J = 6.1 Hz, 1 H, OCHAAr), 4.19 (d, J = 11.1 Hz, 1 H, OCHBAr),
4.43 (d, J = 8.3 Hz, 1 H, OCHAAr), 4.48 (d, J = 8.0 Hz, 1 H,
(S)-2-[(E,4S,6S)-4,6-Bis(4-methoxybenzyloxy)-8-phenyloct-1-enyl]-
oxirane (35): Olefin 12 (0.218 g, 0.47 mmol) was diluted with
OCHBAr), 5.10–5.18 (m, 2 H, CH=CH2), 5.51–5.92 (m, 3 H, CH2Cl2 (10 mL) and degassed for 15 min. Vinyl epoxide (0.099 g,
CH=CH, CH=CH2), 6.83 (d, J = 8.7 Hz, 4 H, ArH), 7.17–7.34 (m,
9 H, ArH, PhH) ppm. 13C NMR (50 MHz, CDCl3): (as a dia-
stereomeric mixture, dr = 2:1): δ = 29.9, 31.2, 31.3, 31.5, 35.8,
36.83, 36.89, 39.9, 41.9, 55.2, 70.3, 70.6, 71.6, 71.69, 74.64, 74.88,
74.96, 113.7, 117.98, 118.0, 125.7, 127.4, 127.5, 128.32, 128.37,
1.42 mmol) was then added to the reaction flask followed by the
catalyst (40 mg, 0.047 mmol). The reaction was allowed to reflux
for eighteen hours under argon, at which time, it was allowed to
oxidize by opening the reaction to air and stirring overnight. The
dark brown solution was then concentrated and purified by flash
Eur. J. Org. Chem. 2010, 6993–7004
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7001