The Journal of Organic Chemistry
Article
chromatography (hexanes/ethyl acetate = 10/1) to give ketone 20
(648 mg, 1.00 mmol, 86%) as colorless oil: IR (thin film, cm−1) 2928,
2857, 1688, 1620, 1463, 1359, 1093; H NMR (300 MHz, CDCl3) δ
123.2, 77.0, 61.2, 60.1, 56.4, 50.8, 48.4, 44.6, 44.3, 44.0, 39.1, 31.3,
27.3, 19.3, 19.2, 14.1; HRMS (ESI) calcd for C22H34O6Na+ [M + Na]+
417.2253, obsd 417.2242.
1
7.76−7.55 (m, 4H), 7.50−7.30 (m, 6H), 6.03 (s, 1H), 5.35 (t, J = 6.1
Hz, 1H), 4.25−4.03 (m, 2H), 3.78 (t, J = 6.5 Hz, 2H), 3.38 (s, 1H),
3.22 (s, 3H), 2.56 (dd, J = 17.0, 9.1 Hz, 1H), 2.33 (t, J = 6.4 Hz, 2H),
2.24 (dd, J = 17.0, 2.7 Hz, 1H), 2.19−1.91 (m, 5H), 1.70−1.52 (m,
3H), 1.45 (s, 3H), 1.37−1.12 (m, 3H), 1.04 (s, 9H), 0.88 (s, 9H), 0.04
(s, 6H); 13C NMR (75 MHz, CDCl3) δ 201.3, 154.3, 138.8, 135.4,
133.5, 129.6, 127.6, 126.6, 125.6, 76.9, 61.8, 60.0, 56.4, 46.5, 44.2, 44.0,
39.1, 31.2, 27.5, 26.7, 25.9, 19.6, 19.3, 19.1, 18.2, 12.3, −5.1; HRMS
(ESI) calcd for C40H62O4Si2Li+ [M + Li]+ 669.4347, obsd 669.4343.
(E)-3-((1R,2S,3R)-2-((E)-6-((tert-Butyldiphenylsilyl)oxy)-4-
methyl-2-oxohex-3-en-1-yl)-3-methoxycyclohexyl)but-2-enal
(21). To a solution of 20 (621 mg, 0.937 mmol) in ethanol (15 mL)
was added PPTS (70 mg, 0.28 mmol). The solution was maintained at
30 °C for 2 h before it was concentrated. The residue was filtered
through a pad of silica gel (hexanes/ethyl acetate = 10/1 to 1/1). The
filtrate was concentrated and the residue was taken into DMSO (15
mL). The solution was treated with IBX (444 mg, 1.59 mmol) and
stirred at room temperature for 2 h before it was extracted with diethyl
ether (3 × 50 mL). The combined ether phase was washed with brine
(20 mL), dried over Na2SO4, filtered, and concentrated. The residue
was purified by column chromatography to give aldehyde 21 (440 mg,
86% over two steps) as colorless oil: IR (thin film, cm−1) 2931, 2857,
1670, 1620, 1427, 11359, 1196, 1090; 1H NMR (300 MHz, CDCl3) δ
9.96 (d, J = 8.0 Hz, 1H), 7.80−7.54 (m, 4H), 7.39 (m, 6H), 6.02 (d, J
= 1.2 Hz, 1H), 5.89 (dd, J = 8.0, 1.1 Hz, 1H), 3.79 (t, J = 6.4 Hz, 2H),
3.41 (d, J = 3.0 Hz, 1H), 3.22 (s, 3H), 2.63 (dd, J = 16.9, 8.9 Hz, 1H),
2.45−2.27 (m, 3H), 2.27−2.12 (m, 2H), 2.12−1.95 (m, 7H), 1.74−
1.48 (m, 3H), 1.34 (m, 3H), 1.02 (s, 9H); 13C NMR (75 MHz,
CDCl3) δ 200.2, 191.2, 166.5, 155.5, 135.5, 133.5, 129.7, 128.5, 127.7,
125.3, 76.6, 61.7, 56.5, 47.8, 44.1, 44.0, 38.8, 31.1, 27.3, 26.8, 19.5,
19.3, 19.2, 14.2 (one carbon missing); HRMS (ESI) calcd for
C34H47O4Si+ [M + H]+ 547.3244, obsd 547.3265.
(1E,3Z,9E,12aS,13R,16aR)-3-Hydroxy-13-methoxy-1,9-di-
methyl-7,8,12a,13,14,15,16,16a-octahydro-5H-benzo[g][1]-
oxacyclotetradecine-5,11(12H)-dione (24). A solution of alcohol
22 (50 mg, 0.127 mmol) in anhydrous toluene (69 mL) was refluxed
under a N2 atmosphere for 20 h before it was concentrated in vacuo.
Purification by column chromatography (silica gel, hexane/EtOAc =
2/1) gave lactone 24 as colorless oil (33 mg, 76%): IR (thin film,
cm−1) 2934, 1741, 1682, 1620,1368, 1276, 1090; 1H NMR (300 MHz,
CDCl3) δ 6.21 (s, 1H), 5.93 (d, J = 1.2 Hz, 1H), 4.55 (ddd, J = 11.3,
6.9, 4.2 Hz, 1H), 4.09 (ddd, J = 11.7, 7.8, 4.2 Hz, 1H), 3.46 (d, J = 12.3
Hz, 1H), 3.39 (s, 1H), 3.30 (s, 3H), 3.24 (d, J = 12.3 Hz, 1H), 2.68
(dd, J = 15.8, 8.5 Hz, 1H), 2.52 (ddd, J = 11.0, 7.3, 4.7 Hz, 1H), 2.46−
2.33 (m, 1H), 2.33−2.17 (m, 2H), 2.17−1.99 (m, 5H), 1.92 (d, J = 0.9
Hz, 3H), 1.58−1.44 (m, 3H), 1.33 (ddd, J = 16.9, 13.0, 5.3 Hz, 2H);
13C NMR (75 MHz, CDCl3) δ 199.4, 190.4, 166.7, 166.7, 152.8, 126.1,
123.6, 80.5, 61.1, 56.5, 51.8, 50.4, 48.0, 40.2, 39.1, 30.2, 27.5, 19.1,
+
19.0, 16.8.; HRMS (ESI) calcd for C20H29O5 [M + H]+ 349.2015,
obsd 349.2012.
(4aR,4bS,6aS,7R,10aR,10bS)-12-Hydroxy-7-methoxy-4a,10b-
dimethyl-4,4a,4b,6,6a,7,8,9,10,10a,10b,11-dodecahydro-1H-
naphtho[2,1-f ]isochromene-1,5(3H)-dione (25). To a solution of
TBAF (1 M in THF, 33 μL, 0.033 mmol) in THF (0.5 mL) was added
lactone 24 (6.7 mg, 0.017 mmol) in THF (0.83 mL) at −78 °C over 1
min via a cannula, which was further rinsed with DMF (1.14 mL). The
reaction was allowed to 0 °C and stirred for 3 h before it was
quenched with satd aq NH4Cl (0.5 mL) and extracted with EtOAc (3
× 20 mL). The combined organic phases were washed with brine,
dried with MgSO4, and concentrated in vacuo. The residue was
purified by column chromatography (silica gel, hexanes/ethyl acetate
=2/1) to give polycyclic compound 25 (5.4 mg, 93%): IR (thin film,
1
cm−1) 2940, 1706, 1643, 1211, 1093; H NMR (300 MHz, CDCl3) δ
13.03 (s, 1H), 4.69−4.50 (m, 1H), 4.47−4.31 (m, 1H), 3.31 (s, 3H),
3.18 (s, 1H), 2.84−2.62 (m, 1H), 2.37 (d, J = 2.9 Hz, 2H), 2.26 (ddd, J
= 19.0, 11.9, 4.1 Hz, 2H), 2.09 (d, J = 12.3 Hz, 1H), 1.75 (d, J = 12.6
Hz, 2H), 1.68−1.56 (m, 2H), 1.53−1.36 (m, 4H), 1.20 (dd, J = 20.7,
9.4 Hz, 3H), 1.04 (s, 3H), 0.88 (s, 1H); 13C NMR (75 MHz, CDCl3)
δ 210.5, 171.0, 170.1, 102.3, 78.0, 66.2, 62.9, 56.7, 47.4, 45.5, 42.8,
41.8, 40.3, 35.9, 33.3, 27.7, 24.8, 21.9, 19.5, 18.8, 13.4; HRMS (ESI)
(E)-Ethyl 5-((1R,2S,3R)-2-((E)-6-((tert-Butyldiphenylsilyl)oxy)-
4-methyl-2-oxohex-3-en-1-yl)-3-methoxycyclohexyl)-3-oxo-
hex-4-enoate (21S). To a solution of aldehyde 21 (58 mg, 0.105
mmol) and ethyl diazoacetate (51.3 μL, 0.42 mmol) in dichloro-
methane (3 mL) was added tin(II) chloride (25 mg, 0.133 mmol).
The mixture was stirred at 30−35 °C overnight before it was
concentrated. The residue was purified by column chromatography to
give β-keto ester 21S (36 mg, 0.057 mmol, 54%) a mixture (∼10:1) of
+
calcd for C20H29O5 [M + H]+ 349.2015, obsd 349.2022.
(1Z,9E,12aS,16aR)-9-(2-((4-Methoxybenzyl)oxy)ethyl)-1,15-
dimethyl-7,8,12,12a,16,16a-hexahydro-3H-benzo[g][1]-
oxacyclotetradecine-3,5,11,13(4H)-tetraone (28). A solution of
alcohol 268 (0.62 g, 1.1 mmol) in toluene (350 mL) was refluxed
under an N2 atmosphere for 19 h before it was concentrated in vacuo.
The residue was purified by silica gel column chromatography
(hexanes/ethyl acetate = 1/1 to 1/2) to give lactones 27 (0.27 g, 46%)
1
its keto and enol forms: H NMR (300 MHz, CDCl3) δ 12.22 (s,
0.1H), 7.72−7.58 (m, 4H), 7.49−7.31 (m, 6H), 6.12 (s, 1H), 6.04 (s,
1H), 6.01 (s, 1H), 5.61 (s, 0.1H), 4.91 (s, 0.1H), 4.17 (dt, J = 8.3, 6.6
Hz, 2H), 3.77 (td, J = 6.4, 2.6 Hz, 2H), 3.42 (s, 3H), 3.21 (s, 3H), 2.60
(dd, J = 16.7, 9.0 Hz, 1H), 2.32 (dd, J = 12.5, 6.2 Hz, 2H), 2.28−2.11
(m, 3H), 2.05 (m, 6H), 1.99 (m, 2H), 1.93−1.88 (m, 1H), 1.79−1.71
(m, 1H), 1.67−1.46 (m, 1 H), 1.38 (m, 1H), 1.33−1.19 (m, 3H), 1.02
(s, 9H); 13C NMR (75 MHz, cdcl3) δ 200.32, 192.11, 167.62, 164.58,
155.46, 135.52, 133.52, 129.70, 127.68, 125.29, 123.14, 61.79, 61.14
(two carbons missing due to signal overlapping); HRMS (ESI) calcd
for C38H52O6SiLi+ [M + Li]+ 639.3693, found 639.3703.
1
and 28 (57 mg, 6%) as colorless oil. Compound 28: H NMR (300
MHz, CDCl3) δ 7.25−7.18 (m, 2H), 6.90−6.81 (m, 2H), 6.07 (s, 1H),
5.96 (s, 1H), 5.95 (dd, J = 2.3, 1.3 Hz, 1H), 4.62 (td, J = 11.4, 3.7 Hz,
1H), 4.58−4.44 (m, 1H), 4.41 (s, 2H), 4.08 (ddd, J = 11.2, 4.7, 3.1 Hz,
1H), 3.79 (s, 3H), 3.69 (dt, J = 9.1, 5.7 Hz, 1H), 3.62−3.50 (m, 1H),
3.46 (d, J = 13.0 Hz, 1H), 3.30−3.15 (m, 2H), 3.15−2.96 (m, 2H),
2.75−2.58 (m, 1H), 2.58−2.48 (m, 2H), 2.48−2.32 (m, 2H), 2.02 (dd,
J = 17.7, 4.4 Hz, 1H), 1.95 (s, 3H), 1.82 (dd, J = 5.9, 1.3 Hz, 3H); 13C
NMR (125 MHz, CDCl3) δ 198.4, 198.0, 190.3, 166.6, 162.0, 160.4,
159.1, 153.9, 130.3, 129.2, 128.7, 125.8, 124.8, 113.7, 72.6, 69.5, 61.0,
55.3, 52.8, 45.5, 42.1, 41.4, 38.9, 34.1, 31.2, 24.3, 21.6; HRMS (ESI)
calcd for C29H34O7Li+ [M + Li]+ 501.2465, obsd 501.2441.
(Z)-7-((tert-Butyldimethylsilyl)oxy)-3-methylhept-2-en-1-ol
(30S1). A solution of DIBAL-H in toluene (1 M, 50.6 mL, 50.6 mmol)
was added to a stirred solution of 30 (6.2 g, 20.6 mmol) in CH2Cl2
(30 mL) at −78 °C dropwise and stirred at the same temperature for
30 min. The reaction was quenched with MeOH (10 mL) followed by
satd aq potassium sodium tartrate (30 mL) at 0 °C. The mixture was
allowed to room temperature and filtered through a pad of Celite with
ethyl acetate (100 mL) as the eluent. The combined filtrate was
concentrated in vacuo, and the residue was purified by silica gel column
(E)-Ethyl 5-((1R,2S,3R)-2-((E)-6-Hydroxy-4-methyl-2-oxohex-
3-en-1-yl)-3-methoxycyclohexyl)-3-oxohex-4-enoate (22). To a
solution of β-keto ester 21S (192 mg, 0.304 mmol) in THF (17 mL)
were added a solution of TBAF in THF (1 M, 1.22 mL, 1.22 mmol)
and acetic acid (70 μL, 1.22 mmol) at 0 °C. The solution was allowed
to warm room temperature over 2 h and stirred until the reaction was
complete as indicated by TLC. The solution was concentrated in
vacuo, and the residue was purified by column chromatography to give
alcohol 22 as colorless oil (59 mg, 50%): IR (thin film, cm−1) 3470,
1
2937, 1714, 1682, 1608; H NMR (300 MHz, CDCl3) δ 12.21 (s,
0.23H, enol form), 6.10 (d, J = 0.9 Hz, 1H), 6.06 (d, J = 1.1 Hz, 1H),
4.18 (q, J = 7.1 Hz, 2H), 3.78 (t, J = 6.2 Hz, 2H), 3.43 (s, 3H), 3.41 (s,
1H), 3.25 (s, 3H), 2.57 (dd, J = 17.7, 8.8 Hz, 1H), 2.36 (t, J = 6.2 Hz,
2H), 2.22 (m, 2H), 2.17−2.10 (m, 3H), 2.09−1.94 (m, 4H), 1.77 (m,
2H), 1.66−1.44 (m, 3H), 1.38 (m,1H), 1.26 (t, J = 7.1 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 200.3, 192.2, 167.8, 164.6, 154.6, 125.5,
8940
dx.doi.org/10.1021/jo301287z | J. Org. Chem. 2012, 77, 8933−8945