Formal Total Synthesis of the Antitubercular Agent Erogorgiaene
dition of DIBAL-H, the reaction mixture was brought to 0 °C and
stirred for 30 min. The reaction mass was quenched with saturated
aqueous sodium–potassium tartrate solution (10 mL) at 0 °C and
stirred for 3 h at room temperature. The organic layer was sepa-
rated, and the aqueous layer was extracted with dichloromethane
(3ϫ15 mL). The combined organic phases were washed with brine
(15 mL) and dried with anhydrous Na2SO4. After evaporation of
the solvent under vacuum, the crude product was subjected to flash
column chromatography (silica gel, 10% EtOAc/hexane) to obtain
pure allylic alcohol 11 (2.13 g, 95%). Rf = 0.6 (silica gel, 20%
139.0, 140.1 ppm. MS (ESI): m/z: 227 [M + Na]+. HRMS (ESI):
calcd. for C14H20ONa [M + Na] 227.1411; found 227.1402.
+
2-[(1R,4S)-4,7-Dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl]acetic
Acid (13): TEMPO (0.352 g, 2.25 mmol) and BAIB (6.35 g,
19.74 mmol) were added to a vigorously stirred solution of 12
(1.15 g, 5.63 mmol) in CH2Cl2 (10 mL) and H2O (3 mL) at 0 °C.
The reaction mixture was allowed to stir for 4 h at room tempera-
ture followed by quenching with saturated solution of Na2S2O3
(10 mL). The organic layer was separated, and the aqueous phase
was extracted with dichloromethane (2 ϫ10 mL). The combined
organic phases were washed with brine (15 mL) and dried with
anhydrous Na2SO4. After evaporation of the solvent under vac-
uum, the crude acid was subjected to flash column chromatography
(silica gel, 12% EtOAc/hexane) to obtain acid 13 (0.99 g, 81%). Rf
= 0.3 (silica gel, 20% EtOAc/hexane). [α]2D6 = +22.5 (c = 0.4,
EtOAc/hexane). [α]2D5 = + 40.5 (c = 1.2, CHCl ). IR (neat): ν =
˜
3
3359, 2922, 1513, 1451, 971, 815 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 1.22 (d, J = 6.8 Hz, 3 H), 1.63 (q, J = 6.8 Hz, 2 H),
1.83–2.0 (m, 2 H), 2.31 (s, 3 H), 2.57–2.71 (m, 1 H), 4.0 (d, J =
4.7 Hz, 2 H), 5.47–5.65 (m, 2 H), 7.02 (d, J = 4.5 Hz, 4 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 20.9, 22.4, 30.2, 37.6, 38.9, 63.6,
126.8, 128.8, 128.9, 133.0, 135.2, 144.1 ppm. MS (ESI): m/z = 227
[M + Na]+. HRMS (ESI): calcd. for C14H20ONa [M + Na]+
227.1411; found 227.1403.
CHCl ). IR (neat): ν = 3437, 2925, 1709, 1455, 812 cm–1. 1H NMR
˜
3
(300 MHz, CDCl3): δ = 1.25 (d, J = 7.0 Hz, 3 H), 1.47–1.56 (m, 1
H), 1.61–1.69 (m, 1 H), 1.91–2.13 (m, 2 H), 2.3 (s, 3 H), 2.57 (dd,
J = 10.1, 15.1 Hz, 1 H), 2.74 (dd, J = 4.3, 15.1 Hz, 1 H), 2.87–2.95
(m, 1 H), 3.27–3.35 (m, 1 H), 6.98 (br. s, 2 H), 7.08 (d, J = 7.9 Hz,
1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 20.9, 23.3, 24.1, 26.9,
31.8, 34.5, 41.7, 127.2, 128.6, 128.8, 135.2, 138.2, 139.1, 178.6 ppm.
MS (ESI): m/z = 241 [M + Na]+. HRMS (ESI): calcd. for
C14H18O2Na [M + Na]+ 241.1204; found 241.1207.
(1S,4R)-1,6-Dimethyl-4-vinyl-1,2,3,4-tetrahydronaphthalene (5): To
a stirred solution of allylic alcohol 11 (2.0 g, 9.8 mmol) in anhy-
drous DCM (20 mL) under a nitrogen atmosphere was added
freshly distilled BF3·OEt2 (1.2 mL, 9.8 mmol) at –78 °C. The reac-
tion mixture was allowed to attain room temperature and then
quenched with saturated NaHCO3 solution (8 mL). The reaction
mixture was extracted with DCM (2ϫ10 mL), the combined DCM
layer was dried with Na2SO4, and the solvents were evaporated.
The crude product was purified by silica gel column chromatog-
raphy (hexane) to afford compound 5 (1.44 g, 79%) as a colorless
oil with good diastereoselectivity (8:1, based on NMR spectro-
(R)-4-Benzyl-3-{2-[(1R,4S)-4,7-dimethyl-1,2,3,4-tetrahydro-
naphthalen-1yl]acetyl}oxazolidin-2-one (15): To a stirred solution of
acid 13 (0.9 g, 4.13 mmol) and Et3N (1.43 mL, 10.3 mmol) in anhy-
drous THF (8 mL) at –20 °C was added pivaloyl chloride (1.0 mL,
8.26 mmol) dropwise, and the mixture was stirred for 1 h. Anhy-
drous LiCl (0.26 g, 6.19 mmol) was then added, and the mixture
was stirred for 30 min. To this, a solution of auxiliary 14 (0.95 g,
5.37 mmol) in anhydrous THF was added, and the mixture was
allowed to stir for 1 h at –20 °C then allowed to attain room tem-
perature. After stirring at ambient temperature for 2 h, the reaction
mixture was quenched with saturated aqueous NH4Cl solution
(7 mL). The organic layer was separated, and the aqueous layer
was extracted with ethyl acetate (2ϫ10 mL). The combined or-
ganic layer was washed with brine (25 mL) and dried with Na2SO4,
and the solvents were evaporated. The crude product was subjected
to column chromatography (silica gel, 5% EtOAc/hexane) to obtain
imide compound 15 (1.45 g, 93%). Rf = 0.4 (silica gel, 10% EtOAc/
scopic data). Rf = 0.85 (silica gel, hexane). [α]2D5 = –15.8 (c = 0.6,
1
CHCl ). IR (neat): ν = 2926, 1635, 1453, 911, 813 cm–1. H NMR
˜
3
(300 MHz, CDCl3): δ = 1.27 (d, J = 7.0 Hz, 3 H), 1. 46 (dd, J =
6.8, 9.0 Hz, 1 H), 1.55–1.66 (m, 1 H), 1.70–1.91 (m, 1 H), 2.0 (dd,
J = 5.2, 9.8 Hz, 1 H), 2.28 (s, 3 H), 2.79–2.95 (m, 1 H), 3.33–3.48
(m, 1 H), 4.95–5.13 (m, 2 H), 5.76–5.96 (m, 1 H), 6.97 (d, J =
7.3 Hz, 2 H), 7.12 (d, J = 7.5 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 20.9, 22.8, 27.7, 29.3, 32.3, 44.1, 114.7, 126.9, 127.8,
129.8, 134.8, 137.6, 138.9, 143.0 ppm.
2-[(1R,4S)-4,7-Dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl]ethanol
(12): Compound 5 (1.35 g, 7.26 mmol) in dry THF (15 mL) was
charged into a 100-mL, two-necked round-bottomed flask
equipped with a magnetic spin bar, a nitrogen inlet, and a septum.
To this flask was added 9-BBN (0.5 m in THF, 29 mL, 14.51 mmol)
dropwise at 0 °C, and the mixture was stirred for 15 h at room
temperature. After complete consumption of the starting com-
pound, the reaction mixture was quenched with 3 n NaOH (10 mL)
at 0 °C, followed by the addition of 30% H2O2 (15 mL) dropwise,
and the resulting solution was stirred for 6 h at room temperature.
The organic phase was separated, and the aqueous layer was ex-
tracted with ethyl acetate (3ϫ15 mL). The combined organic phase
was washed with brine (1 ϫ 30 mL) and dried with anhydrous
Na2SO4, and the solvent was evaporated under reduced pressure.
The crude product was subjected to flash column chromatography
(silica gel, 10% EtOAc/hexane) to obtain pure primary alcohol 12
hexane). [α]2D5 = –43.7 (c = 0.8, CHCl ). IR (neat): ν = 2924, 1783,
˜
3
1700, 1382, 1209, 702 cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.25
(d, J = 6.8 Hz, 3 H), 1.46–1.70 (m, 3 H), 1.98–2.13 (m, 2 H), 2.28
(s, 3 H), 2.80 (dd, J = 9.8, 12.8 Hz, 1 H), 2.86–3.01 (m, 1 H), 3.22–
3.29 (m, 1 H), 3.34 (dd, J = 3.7, 12.8 Hz, 1 H), 3.38–3.50 (m, 1 H),
4.15–4.22 (m, 2 H), 4.65–4.78 (m, 1 H), 6.93–7.18 (m, 3 H), 7.20–
7.39 (m, 5 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0, 23.5,
24.0, 26.8, 31.7, 34.1, 38.0, 42.6, 55.3, 66.1, 127.1, 127.3, 128.6,
128.9, 129.0, 129.4, 135.1, 135.3, 138.4, 139.2, 153.3, 172.3 ppm.
MS (ESI): m/z = 378[M + H]+. HRMS (ESI): calcd. for C24H27NO3
Na [M + Na]+ 400.1888; found 400.1897.
(R)-4-Benzyl-3-{(R)-2-[(1R,4S)-4,7-dimethyl1,2,3,4-tetrahydronaph-
thalen-1-yl]propanoyl}oxazolidin-2-one (16): To a stirred solution of
15 (1.35 g, 3.58 mmol) in anhydrous THF (15 mL) under a nitrogen
atmosphere was added LiHMDS (1.06 m in THF, 6.75 mL,
7.16 mmol) at 0 °C. After stirring for 0.5 h, methyl iodide (0.56 mL,
(1.30 g, 88%). Rf = 0.6 (silica gel, 20% EtOAc/hexane). [α]2D5
+18.7 (c = 0.7, CHCl ). IR (neat): ν = 3362, 2928, 1453, 1054,
=
˜
3
1
814 cm–1. H NMR (300 MHz, CDCl3): δ = 1.24 (d, J = 7.0 Hz, 3 8.95 mmol) was added, and the mixture was stirred for another
H), 1.39–1.66 (m, 2 H), 1.71–2.05 (m, 4 H), 2.3 (s, 3 H), 2.80–2.97, 0.5 h. The reaction mixture was quenched with saturated aqueous
(m, 2 H), 3.77, (dd, J = 6.2, 7.3 Hz, 2 H), 6.92–7.01 (m, 2 H), 7.07, NH4Cl solution (8 mL), the organic layer was separated, and the
(d, J = 7.5 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0,
aqueous layer was extracted with ethyl acetate (2ϫ15 mL). The
23.4, 23.8, 27.3, 31.9, 34.3, 39.9, 61.1, 126.6, 128.3, 129.2, 134.9,
combined organic layer was washed with brine (20 mL) and dried
Eur. J. Org. Chem. 2012, 2072–2076
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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