Ru-Catalyzed Redox Isomerization of Propargylic Alcohols
A R T I C L E S
0.03 mmol) was added, and the solution was brought to reflux in
a preheated oil bath. After 2 h, the mixture was diluted with ether
and filtered through florisil to remove the catalyst. Removal of the
solvent under reduced pressure and flash chromatography on silica
gel (20:1 petroleum ether:ethyl acetate) gave 163 mg of clear oil
(74% yield). The product appeared to decompose via electrocyclic
rearrangement upon standing at room temperature for several days.
IR (film): 2930, 2859, 1688, 1662, 1626, 1597, 1458, 1317, 1190,
1072, 974 cm-1. 1H NMR (300 MHz, CDCl3): δ 7.15 (d, J ) 15.9
Hz, 1H), 6.21 (s, 1H), 6.07 (d, J ) 16.1 Hz, 1H), 2.56 (t, J ) 7.7
Hz, 2H), 2.23-2.15 (m, 4H), 1.72-1.60 (m, 6H), 1.34-1.29 (m,
6H), 0.88 (t, J ) 6.6 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ
201.4, 145.9, 139.7, 135.2, 123.2, 40.5, 31.6, 29.0, 26.6, 24.5, 24.1,
22.5, 22.0 (2), 14.0. HRMS: calcd for C15H24O (M+), 220.1827;
found, 220.1829.
mL) and oxidized by slow addition of 30% hydrogen peroxide (14.4
mL). Gas chromatography showed roughly 20:1 selectivity for the
desired isomer. The mixture was worked up with water (400 mL)
and ether (4 × 100 mL), and the combined extracts were dried
over magnesium sulfate. Removal of the solvent under reduced
pressure and flash chromatography on silica gel (10:1 petroleum
ether:ethyl acetate) gave 13.39 g of clear oil (67% yield). IR (film):
3416, 2957, 2931, 2859, 2218, 1636, 1255, 1085, 837, 779 cm-1
.
1H NMR (300 MHz, CDCl3): δ 6.16 (dd, J ) 15.9, 5.5 Hz, 1H),
5.80 (dd, J ) 15.9, 1.6 Hz, 1H), 4.43 (d, J ) 1.7 Hz, 2H), 4.27 (t,
J ) 5.4 Hz, 1H), 2.51-2.35 (m, 2H), 2.22 (br, 1H), 2.19-2.13
(m, 2H), 1.54-1.40 (m, 2H), 1.38-1.12 (m, 4H), 0.91 (s, 9H),
0.90 (t, J ) 6.7 Hz, 3H), 0.13 (s, 6H). 13C NMR (75 MHz, CDCl3):
δ 143.5, 110.3, 88.8, 83.9, 82.6, 74.8, 70.2, 52.1, 31.0, 28.6, 27.8,
25.8 (3), 22.2, 18.6, 18.3, 13.9, -5.2 (2). Anal. Calcd for
C20H34O2Si: C, 71.80; H, 10.24. Found: C, 71.68; H, 9.96.
(E)-6-(tert-Butyldimethylsilyl)oxy-2-hexen-4-yn-1-ol. To 6-(tert-
butyldimethylsilyl)oxy-2,4-hexadiyn-1-ol (16.43 g, 73.35 mmol) in
THF (150 mL) was added Red-Al (65% solution in toluene, 33.03
mL, 34.22 g, 110 mmol) at 0 °C. Reduction was complete after
stirring for 1 h at room temperature, and the reaction was quenched
at 0 °C with ethyl acetate (50 mL). The reaction was worked up
with 3 M sulfuric acid (300 mL) and ether (4 × 250 mL). The
combined extracts were washed with saturated aqueous sodium
bicarbonate (100 mL) and brine (100 mL) and dried over
magnesium sulfate. Removal of the solvent under reduced pressure
and flash chromatography on silica gel (5:1 petroleum ether:ethyl
acetate) gave 14.53 g of clear oil (88% yield). IR (film): 3360,
2956, 2930, 2858, 2218, 1635, 1472, 1363, 1256, 1086, 835, 779
cm-1. 1H NMR (300 MHz, CDCl3): δ 6.23 (dt, J ) 15.9, 5.1 Hz,
1H), 5.76 (dt, J ) 15.9, 1.6 Hz, 1H), 4.43 (d, J ) 1.7 Hz, 2H),
4.20 (br, 2H), 1.96 (br, 1H), 0.91 (s, 9H), 0.13 (s, 6H). 13C NMR
(75 MHz, CDCl3): δ 141.8, 109.9, 88.4, 82.7, 62.7, 52.1, 25.8 (3),
18.3, -5.2 (2). HRMS: calcd for C12H21O2Si (M+ - H), 225.1311;
found, 225.1308.
(E)-6-(tert-Butyldimethylsilyl)oxy-2-hexen-4-ynal (17). To ox-
alyl chloride (6.28 mL, 9.14 g, 72 mmol) in methylene chloride
(150 mL) at -78 °C was slowly added DMSO (6.39 mL, 7.03 g,
90 mmol). After stirring 10 min, a precooled solution of the above
alcohol (13.56 g, 60 mmol) in methylene chloride (50 mL) was
added via cannula. After 10 min, triethylamine (25.09 mL, 18.21
g, 180 mmol) was slowly added and stirring was continued at -78
°C for 30 min. After warming and stirring at room temperature for
30 min, the mixture was diluted with methylene chloride (200 mL)
and washed with 10% sodium bisulfate. After removal of the solvent
under reduced pressure, the residue was dissolved in ether (250
mL) and washed with saturated sodium bicarbonate (100 mL) and
water (2 × 100 mL). Drying over magnesium sulfate and removal
of the solvent under reduced pressure followed by filtration through
silica gel (10:1 petroleum ether:ethyl acetate) gave 11.31 g of clear
oil (84% yield). IR (film): 2956, 2930, 2858, 2729, 2213, 1689,
1606, 1256, 1089, 837, 779 cm-1. 1H NMR (300 MHz, CDCl3): δ
9.57 (d, J ) 7.6 Hz, 1H), 6.63 (dt, J ) 15.9, 1.8 Hz, 1H), 6.44 (dd,
J ) 15.9, 7.8 Hz, 1H), 4.53 (d, J ) 1.7 Hz, 2H), 0.92 (s, 9H), 0.14
(s, 6H). 13C NMR (75 MHz, CDCl3): δ 193.0, 139.6, 132.1, 103.2,
81.3, 52.2, 25.7 (3), 18.3, -5.2 (2). Anal. Calcd for C12H20O2Si:
C, 64.23; H, 8.99. Found: C, 64.06; H, 9.16.
(2E,4E)-6-(tert-Butyldiphenylsilyl)oxy-2,4-tetradecadien-
8-ynal (21). To (E)-6-(tert-butyldiphenylsilyl)oxy-4-tetradecene-
2,8-diyn-1-ol (916 mg, 2.00 mmol) in THF (10 mL) were added
indenyl catalyst 2 (77 mg, 0.10 mmol) and camphorsulfonic acid
(32 mg, 0.10 mg). The solution was sparged with argon for several
minutes, and indium triflate (56 mg, 0.10 mmol) was added. The
solution was brought to reflux in a preheated oil bath, and the
reaction was monitored by thin-layer chromatography. Isomerization
was complete within 20 min, at which point the solution was filtered
through florisil with ether to remove the catalyst. Removal of the
solvent under reduced pressure and flash chromatography on silica
gel (10:1 petroleum ether:ethyl acetate) gave 845 mg of clear oil
(92% yield). IR (film): 3072, 2958, 2932, 2859, 2732, 1688, 1646,
1428, 1106, 1009, 988, 741, 702 cm-1 1H NMR (300 MHz,
.
CDCl3): δ 9.53 (d, J ) 8.1 Hz, 1H), 7.73-7.60 (m, 4H), 7.46-7.32
(m, 6H), 7.06-6.98 (m, 1H), 6.36-6.32 (m, 2H), 6.03 (dd, J )
15.1, 8.1 Hz, 1H), 4.38 (dt, J ) 9.5, 4.8 Hz, 1H), 2.46-2.28 (m,
2H), 2.10-2.05 (m, 2H), 1.44-1.21 (m, 6H), 1.08 (s, 9H), 0.86 (t,
J ) 7.0 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 193.8, 151.6,
146.0, 135.8 (4), 133.5, 133.3, 131.7, 129.8 (2), 128.0, 127.6 (4),
83.1, 75.3, 72.1, 31.0, 28.5, 28.0, 26.9 (3), 22.2, 19.3, 18.6. HRMS:
calcd for C26H29O2Si (M+ - C4H9), 401.1937; found, 401.1939.
(6Z,8E,10E,14Z)-Methyl 5,12-Bis[(tert-butyldiphenylsilyl)-
oxy]-6,8,10,14-eicosatetraenoate. (8E,10E)-Methyl 5,12-bis[(tert-
butyldiphenylsilyl)oxy]-8,10-eicosadiene-6,14-diynoate (207 mg,
0.25 mmol) and Lindlar catalyst (50 mg) were suspended in ethyl
acetate (50 mL) containing quinoline (590 mL, 646 mg, 5.00 mmol).
The mixture was stirred under an atmosphere of hydrogen, and
reaction progress was carefully monitored by thin-layer chroma-
tography. The first semihydrogenation was complete within 1 h
(monohydrogenated Rf ) 0.34 in 20:1 petroleum ether:ethyl acetate),
but the second required 4 h to reach completion (dihydrogenated
Rf ) 0.39 in 20:1 petroleum ether:ethyl acetate). The mixture was
filtered through florisil with ethyl acetate to remove the catalyst,
and the solution was diluted with petroleum ether (50 mL). The
solution was washed with 1 M aqueous sulfuric acid (25 mL) and
saturated aqueous sodium bicarbonate (50 mL). The extracts were
dried over magnesium sulfate, and the solvent was removed under
reduced pressure. Flash chromatography on silica gel (20:1
petroleum ether:ethyl acetate) gave 191 mg of clear oil (92% yield).
All spectral data compared favorably with those reported in the
literature.18 IR (film): 3015, 2931, 2858, 1742, 1599, 1472, 1428,
1362, 1112, 1074, 998, 822, 740, 702 cm-1. 1H NMR (300 MHz,
CDCl3): δ 7.70-7.58 (m, 8H), 7.40-7.29 (m, 12H), 5.96-5.56
(m, 5H), 5.42-5.20 (m, 3H), 4.47 (br, 1H), 4.15 (br, 1H), 3.63
and 3.61 (s, 3H, diastereomers), 2.28-2.04 (m, 4H), 1.81-1.77
(m, 2H), 1.60-1.42 (m, 4H), 1.28-1.14 (m, 6H), 1.07 and 1.06
(s, 9H, diastereomers), 1.03 and 1.02 (s, 9H, diastereomers), 0.85
(t, J ) 6.1 Hz, 3H).
(E)-1-(tert-Butyldimethylsilyl)oxy-4-tetradecene-2,8-diyn-6-ol
(19). Tripentylborane was prepared by slow addition at 0 °C of
borane dimethyl sulfide complex (30 mL, 2 M in THF, 60.0 mmol)
to 1-pentene (19.73 mL, 12.63 g, 180 mmol) in THF (100 mL).
To propargyl chloride (4.34 mL, 4.47 g, 60 mmol) in ether (100
mL) at -90 °C was added n-butyllithium (37.5 mL, 1.6 M in
hexanes, 60 mmol). After stirring for 10 min, the mixture was
diluted with THF (150 mL), and the tripentylborane solution,
precooled to -78 °C, was transferred via cannula over 30 min.
After stirring for 30 min at -78 °C, a precooled solution of aldehyde
17 (11.31 g, 50.5 mmol) was transferred via cannula, and stirring
was continued 30 min. After warming to room temperature, the
mixture was treated with methanol (30 mL) and 3 N NaOH (21.6
Leukotriene B4. To the above eicosatetraenoate (135 mg, 0.16
mmol) in THF (1.6 mL) at 0 °C was added tetrabutylammonium
fluoride (0.60 mL, 1 M in THF, 1.6 mol). After stirring at room
temperature overnight, the mixture was poured into vigorously
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J. AM. CHEM. SOC. VOL. 130, NO. 36, 2008 11977