OxidatiVe Cyclization Reactions of Trienes and Dienynes
(1S,4E)-1-((2S,5R,)-5-((4R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-tet-
rahydrofuran-2-yl)-pentadec-4-en-1-ol (31). To a solution of triol
29 (326 mg, 0.91 mmol) in 2,2-dimethoxypropane (15 mL) was
added p-TsOH (20 mg), and the resulting mixture was stirred for
2.5 h. The solution was diluted with EtOAc (30 mL) and washed
with H2O (10 mL), saturated aqueous NaHCO3 (2 × 10 mL), and
brine (20 mL). The organic phase was dried (Na2SO4) and
concentrated in vacuo to a colorless oil. Purification by column
chromatography (silica gel, 20% EtOAc/hexane) afforded the title
sessing threo-cis-threo-trans-threo, threo-cis-threo-trans-eryth-
ro, and threo-cis-erythro-cis-threo configurations can be ac-
cessed from trienes or dienynes, and application of the dual
Mn/Re metal oxo-mediated route circumvented the requirement
for hydroxyl group protection during a short synthesis of 21,22-
di-epi-membrarollin (23).
Experimental Section
compound 31 (333 mg, 0.84 mmol, 92%) as a colorless oil: [R]27
D
1
+1.3 (c 0.39, CHCl3); IR νmax (neat) 3476, 2923, 2853 cm-1; H
(2S)-N-((2S)-2-Hydroxy-2-((2R,5S)-5-((1S,4E)-1-hydroxypenta-
dec-4-enyl)-tetrahydrofuran-2-yl)ethanoyl)-camphor-10,2-sultam
(28). To a solution of triene 26 (980 mg, 1.89 mmol) in acetone
(64 mL) and AcOH (16 mL) at 30 °C was added KMnO4 (389 mg,
2.46 mmol). The solution immediately turned purple and then to
brown over ∼5 min. The mixture was stirred between -30 and
-20 °C for 2 h before quenching with saturated aqueous Na2S2O5
(8 mL) and H2O (8 mL). The aqueous phase was extracted with
EtOAc (4 × 15 mL), and the combined organic phases were dried
(Na2SO4) and concentrated in vacuo to a yellow oil. Purification
by column chromatography (silica gel, 20% f 40% EtOAc/hexane)
afforded three different fractions. The major diastereoisomer 28
(611 mg, 1.08 mmol, 57%) was obtained as a thick colorless gum,
the minor diastereoisomer 27 (103 mg, 0.18 mmol, 10%) as a cream
solid, and (2S)-N-((2R/S,6E,10E)-2-hydroxy-3-oxohenicosa-6,10-
dienoyl)-camphor-10,2-sultam (124 mg, 0.23 mmol, 12%) as a
NMR (400 MHz, CDCl3) δ 5.45 (1H, dt, J ) 15.3, 5.6 Hz), 5.40
(1H, dt, J ) 15.3, 5.6 Hz), 4.11 (1H, ddd, J ) 7.6, 6.5, 4.8 Hz),
4.02-3.95 (1H, m), 4.01 (1H, t, J ) 7.6 Hz), 3.91-3.85 (1H, m),
3.78 (1H, t, J ) 7.6 Hz), 3.46-3.39 (1H, m), 2.60 (1H, d, J ) 6.5
Hz), 2.26-2.04 (2H, m), 2.02-1.89 (4H, m), 1.86-1.76 (2H, m),
1.63-1.48 (2H, m), 1.45 (3H, s), 1.38 (3H, s), 1.36-1.22 (16H,
m), 0.89 (3H, t, J ) 6.9 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ
131.0, 129.6, 109.6, 82.8, 79.1, 78.0, 73.8, 66.2, 34.1, 32.6, 31.9,
29.6, 29.6, 29.5, 29.3, 29.2, 28.7, 28.1, 28.0, 26.4, 25.5, 22.7, 14.1
ppm; LRMS (ES+) m/z 419 ([M + Na]+), 414 ([M+NH4]+); HRMS
(ES+) for C24H44O4Na+, calcd 419.3132, found 419.3132.
(1S,4S,5S)-1-((2S,5R,)-5-((4R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-
tetrahydrofuran-2-yl)-4,5-dihydroxypentadecan-1-ol (39). To an
t
orange biphasic mixture of H2O (10 mL), BuOH (10 mL), AD-
mix R (2.00 g), and MeSO2NH2 (0.08 g, 0.84 mmol) at 0 °C was
added mono-THF 31 (0.33 g, 0.84 mmol) in Et2O (3 mL) and
tBuOH (3 mL). The resulting orange mixture was stirred for 15 h
before it was quenched with Na2SO3 (2.00 g) and then stirred for
a further 30 min. H2O (15 mL) was added, and the aqueous phase
extracted with EtOAc (4 × 20 mL). The combined organic phases
were washed with 2 M KOH (3 × 15 mL), dried (Na2SO4), and
concentrated in vacuo to an orange oil. Purification by column
chromatography (silica gel, 5% MeOH/CH2Cl2) afforded the title
yellow oil. Data for 28: [R]26 +27.6 (c 0.75, CHCl3); IR νmax
D
1
(neat) 3458, 2956, 2923, 2853, 1696 cm-1; H NMR (400 MHz,
CDCl3) δ 5.50-5.36 (2H, m), 4.62-4.52 (2H, m), 3.97 (1H, dd, J
) 7.8, 4.9 Hz), 3.96-3.91 (1H, m), 3.88 (1H, dt, J ) 7.3, 4.2 Hz),
3.52 (1H, d, J ) 13.7 Hz), 3.51-3.44 (2H, m), 3.45 (1H, d, J )
13.7 Hz), 2.30-2.15 (1H, m), 2.15-2.01 (8H, m), 2.01-1.82 (6H,
m), 1.66-1.41 (2H, m), 1.40-1.22 (16H, m), 1.17 (3H, s), 0.98
(3H, s), 0.89 (3H, t, J ) 6.9 Hz) ppm; 13C NMR (100 MHz, CDCl3)
δ 171.7, 131.2, 129.5, 83.0, 78.7, 73.6, 73.4, 65.8, 53.1, 49.0, 47.9,
44.6, 38.2, 34.5, 32.9, 32.6, 31.9, 29.6, 29.6, 29.5, 29.3, 29.2, 28.8,
28.2, 26.4, 22.7, 20.8, 19.9, 14.1 ppm; LRMS (ES+) m/z 590 ([M
+ Na]+); HRMS (ES+) for C31H53NO6SNa+, calcd 590.3486, found
compound 39 (0.34 g, 0.79 mmol, 94%) as a colorless oil: [R]27
D
+1.44 (c 0.52, CHCl3); IR νmax (neat) 3408, 2922, 2853 cm-1; 1H
NMR (400 MHz, CDCl3) δ 4.10 (1H, ddd, J ) 7.5, 6.3, 4.5),
4.03-3.97 (1H, m), 4.01 (1H, t, J ) 7.5 Hz), 3.92-3.86 (1H, m),
3.78 (1H, t, J ) 7.5 Hz), 3.53 (1H, br s), 3.51-3.37 (3H, m), 3.19
(1H, br s), 2.29 (1H, d, J ) 4.8 Hz), 2.03-1.92 (2H, m), 1.86-1.78
(2H, m), 1.77-1.57 (4H, m), 1.54-1.42 (2H, m), 1.46 (3H, s),
1.38 (3H, s), 1.34-1.21 (16H, m), 0.89 (3H, t, J ) 6.9 Hz) ppm;
13C NMR (100 MHz, CDCl3) δ 109.6, 82.9, 79.1, 78.0, 74.8, 74.3,
66.2, 33.7, 31.9, 30.8, 30.7, 29.7, 29.6, 29.3, 28.2, 28.0, 26.5, 25.7,
25.5, 22.7, 14.1 ppm; LRMS (ES+) m/z 453 ([M + Na]+), 431
([M + H]+); HRMS (ES+) for C24H46O6Na+, calcd 453.3187, found
453.3180.
590.3503. Data for 27: [R]26 +84.7 (c 1.20, CHCl3); IR νmax (neat)
D
3482, 2956, 2922, 2853, 1693 cm-1; 1H NMR (400 MHz, CDCl3)
δ 5.49-5.35 (2H, m), 4.68 (1H, d, J ) 2.3 Hz), 4.50 (1H, ddd, J
) 7.4, 4.9, 2.3 Hz), 3.96 (1H, app t, J ) 6.1 Hz), 3.77 (1H, td, J
) 7.3, 4.5 Hz), 3.54-3.42 (1H, m), 3.50 (1H, d, J ) 13.7 Hz),
3.45 (1H, d, J ) 13.7 Hz), 2.24-1.84 (13H, m), 1.57-1.43 (2H,
m), 1.42-1.20 (18H, m), 1.16 (3H, s), 0.98 (3H, s), 0.89 (3H, t, J
) 6.9 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ 173.1, 131.1, 129.5,
83.0, 80.2, 74.2, 73.0, 64.9, 53.0, 49.0, 47.9, 44.5, 37.6, 34.5, 32.6,
31.9, 29.6, 29.5, 29.3, 29.2, 28.7, 28.2, 27.8, 26.5, 22.7, 20.4, 19.9,
14.1 ppm; LRMS (ES+) m/z 590 ([M + Na]+).
(1R)-1-((2R,5S)-5-((2S,5R)-5-((1S)-1-Hydroxyundecyl)-tetrahy-
drofuran-2-yl)-tetrahydrofuran-2-yl)-ethane-1,2-diol (37). By the
ortho-ester cyclization method: To a solution of mono-THF acetal
39 (57 mg, 0.13 mmol) and trimethylorthoacetate (19 mg, 0.16
mmol) in CH2Cl2 (2 mL) at 0 °C was added BF3 ·OEt2 (2 mg, 0.01
mmol), and the resulting mixture was warmed to room temperature
after 1 h. After 35 h acetone (1 mL) was added, and the mixture
was concentrated in vacuo to a colorless oil. The crude oil was
redissolved in MeOH (3 mL) before K2CO3 (74 mg, 0.52 mmol)
was added, and the mixture was stirred for 4 h before concentrating
in vacuo to a white solid. Purification by column chromatography
(silica gel, 5% MeOH/CH2Cl2) afforded the title compound 37 (34
(1R)-1-((2R,5S)-5-((1S,4E)-1-Hydroxypentadec-4-enyl)-tetrahy-
drofuran-2-yl)-ethane-1,2-diol (29). To a solution of mono-THF 28
(1.00 g, 1.76 mmol) in THF (25 mL) and H2O (25 mL) was added
NaBH4 (0.07 g, 1.94 mmol). The resulting mixture was stirred for
3 h, then H2O (10 mL) was added, and the mixture was extracted
with EtOAc (3 × 100 mL). The combined organic phases were
dried (Na2SO4) and concentrated in vacuo to a cream oil. Purifica-
tion by column chromatography (silica gel, 5% MeOH/CH2Cl2)
afforded the title compound 29 (0.59 g, 1.65 mmol, 94%) as a
colorless oil: [R]27 -10.1 (c 0.44, CHCl3); IR νmax (neat) 3360,
D
2956, 2923, 2853 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.52-5.36
(2H, m), 4.05 (1H, td, J ) 6.8, 3.9 Hz), 3.89 (1H, td, J ) 6.8, 4.5
Hz), 3.75-3.69 (2H, m), 3.59 (1H, m), 3.50 (1H, m), 3.13 (1H, br
s), 2.53 (1H, br s), 2.42 (1H, br s), 2.26-2.05 (2H, m), 2.03-1.85
(6H, m), 1.66-1.48 (2H, m), 1.38-1.22 (16H, m), 0.89 (3H, t, J
) 6.9 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ 131.4, 129.3, 82.8,
80.5, 73.7, 73.6, 65.2, 34.3, 32.6, 31.9, 29.6, 29.6, 29.5, 29.3, 29.2,
28.8, 28.1, 28.0, 22.7, 14.1 ppm; LRMS (ES+) m/z 735 379 ([M +
Na]+); HRMS (ES+) for C21H40O4Na+, calcd 379.2819, found
379.2813.
mg, 0.09 mmol, 71%) as a colorless gum: [R]27 +0.6 (c 1.05,
D
CHCl3); IR νmax (neat) 3404, 2923, 2853 cm-1; 1H NMR (400 MHz,
CDCl3) δ 4.14 (1H, td, J ) 6.0, 3.1 Hz), 4.03-3.97 (1H, m),
3.93-3.83 (3H, m), 3.79-3.66 (3H, m), 3.57-3.50 (1H, m), 3.33
(1H, br s), 2.85 (1H, dd, J ) 8.0, 4.0 Hz), 2.06-1.71 (8H, m),
1.41-1.23 (18H, m), 0.89 (3H, t, J ) 6.9 Hz) ppm; 13C NMR (100
MHz, CDCl3) δ 83.2, 81.6, 80.9, 80.7, 73.5, 71.5, 65.7, 33.1, 31.9,
29.7, 29.6, 29.6, 29.3, 28.6, 28.4, 28.3, 26.0, 23.4, 22.7, 14.1 ppm;
LRMS (ES+) m/z 395 ([M + Na]+), 373 ([M + H]+); HRMS (ES+)
for C21H40O5Na+, calcd 395.2768, found 395.2762.
J. Org. Chem. Vol. 74, No. 3, 2009 987