E
J. Westphal et al.
Paper
Synthesis
5 mol%), and H2O (2.8 mL, 157 mmol, 52 equiv) were added. After 3 h
at r.t., the solution of the in situ generated alkylborane was added and
stirring was continued at 85 °C for 16 h. Then, sat. aq NH4Cl (150 mL)
and MTBE (100 mL) were added and the layers were separated. The
aqueous layer was extracted with MTBE (3 ×) and the combined or-
ganic layers were washed with H2O (2 ×). After drying (MgSO4), the
solvent was evaporated under reduced pressure and the residue was
purified by column chromatography (cHex/EtOAc 50:1) to afford 7
(650 mg, 2.80 mmol, 93%) as a colorless liquid (Rf = 0.72, cHex/EtOAc
10:1). The enantiomeric purity was 94% ee as determined by GC [BGB
6-TBDMS column, 50 to 100 °C (0.1 °C/min); tR = 363 min, 367 min
(main enantiomer)].
8b
Rf = 0.46 (cHex/EtOAc 50:1).
[α]λ20 +32.7 (365 nm), +20.0 (436 nm), +9.06 (546 nm), +7.5 (579 nm),
+6.7 (589 nm) (c = 0.78 g/100 mL in CH2Cl2).
IR (ATR): 2951 (vs), 2900 (s), 2868 (m), 1470 (m), 1448 (s), 1399 (m),
1374 (m), 1363 (m), 1326 (m), 1266 (s), 1150 (m), 1114 (vs), 1024
(m), 1008 (s), 820 cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 5.37 (br s, 1 H, H9), 3.31 (s, 3 H, H15),
2.54 (s, 1 H, H7), 2.02–1.97 (m, 1 H, H2), 1.90–1.89 (m, 1 H, H5), 1.87–
1.83 (m, 2 H, H3), 1.77 (s, 3 H, H14), 1.73–1.63 (m, 1 H, H10), 1.50–
1.45 (m, 2 H, H4), 1.00 (s, 3 H, H12a), 0.89 (s, 3 H, H12b), 0.88 (d, J =
4.9 Hz, 3 H, H13).
20
[α]λ –23 (365 nm), –16.4 (436 nm), –9.8 (546 nm), –8.3 (579 nm),
7.9 (589 nm) (c = 0.79 g/100 mL in CH2Cl2).3
13C NMR (75 MHz, CDCl3): δ = 140.8 (C8), 124.3 (C9), 67.5 (C7), 58.3
(C11), 57.1 (C15), 53.9 (C1), 50.8 (C5), 36.5 (C3), 35.7 (C2), 31.8 (C10),
25.2 (C12a), 23.3 (C4), 22.8 (C12b), 19.1 (C13), 17.7 (C14).
IR (ATR): 2958 (m), 2923 (m), 1611 (m), 1580 (m), 1506 (s), 1464 (s),
1455 (s), 1411 (m), 1286 (m), 1259 (vs), 1191 (m), 1157 (m), 1127
(m), 1098 (m), 1043 (vs), 927 (m), 845 (m), 809 cm–1 (vs).
GC-MS (70 eV): m/z (%) = 232 (10, [M]+), 217 (4, [M – CH3]+), 200 (1),
1H NMR (300 MHz, CDCl3): δ = 7.10 (d, J = 7.7 Hz, 1 H, H6), 6.79 (d, J =
7.7 Hz, 1 H, H5), 6.72 (s, 1 H, H3), 5.17 (t, J = 7.0 Hz, 1 H, CH=), 3.85 (s,
3 H, OCH3), 3.19 (sext, J = 7.0 Hz, 1 H, H2′), 2.38 (s, 3 H, ArCH3), 1.97
(quint, J = 7.2 Hz, 2 H, H4′), 1.73 (s, 3 H, =CCH3), 1.70–1.60 (m, 2 H,
H3′), 1.59 (s, 3 H, =CCH3), 1.23 (d, J = 7.0 Hz, 3 H, H1′).
13C NMR (75 MHz, CDCl3): δ = 157.1 (C2), 136.3 (C4), 133.0 (C1), 131.2
(C6′), 126.7 (C6), 125.0 (C5′), 121.2 (C5), 111.6 (C3), 55.5 (OCH3), 37.3
(C3′), 31.6 (C2′), 26.4 (C4′), 25.9 (vinyl-CH3), 21.5 (ArCH3), 21.2 (C1′),
17.7 (vinyl-CH3).
175 (8), 149 (100), 115 (21), 91 (34).
Cedrenone (9)
To a stirred solution of the mixture 8a/8b (200 mg, 0.86 mmol, 1.0
equiv) in CH2Cl2 (20 mL) under argon at 0 °C was added dropwise Br2
(44 μL, 0.86 mmol, 1.0 equiv). After 0.5 h at 0 °C, all volatiles were re-
moved under reduced pressure and the residue was diluted with n-
pentane (5 mL). Then, HSnBu3 (232 μL, 0.86 mmol, 1.0 equiv) was
added. After 0.5 h at 0 °C, the whole mixture was directly subjected to
column chromatography (n-pentane, ultra pure silica gel) to yield
pure cedrenone 9 (115 mg, 0.53 mmol, 61%) as a colorless oil.
GC-MS (70 eV): m/z (%) = 232 (27, [M]+), 217 (4, [M – CH3]+), 201 (1,
[M – OCH3]+), 149 (100).
[α]λ20 –29.4 (546 nm), –25.1 (579 nm), –24.6 (589 nm) (c = 0.37 g/100
mL in CH2Cl2).
Photocyclization Products 8a and 8b
IR (ATR): 2944 (s), 2866 (m), 1739 (vs), 1455 (m), 1377 (m), 1279 (m),
1217 (m), 1148 (m), 1035 (s), 981 (s), 944 (m), 846 (m), 678 cm–1 (m).
Compound 7 (200 mg, 0.86 mmol, 1.0 equiv) was dissolved in MTBE
(40 mL, c = 0.02 M) and exposed to the light from a Rayonet photore-
actor (254 nm, 250 W) for 6 h. Afterwards, the solvent was removed
and the residue was subjected to column chromatography (cHex/EtO-
Ac 50:1). Compound 8a and 8b were isolated in a combined yield of
168 mg (0.72 mmol, 84%) as a yellow oil. Analytically pure samples of
both isomers were obtained from early and late fractions, respective-
ly.
1H NMR (300 MHz, CDCl3): δ = 5.36 (dd, J = 2.6, 1.1 Hz, 1 H, H9), 2.53–
2.36 (m, 2 H, H10), 2.32 (dd, J = 4.3, 2.1 Hz, 1 H, H2), 2.20 (dd, J = 8.6,
5.0 Hz, 1 H, H5), 2.07 (s, 1 H, H7), 1.72 (s, 3 H, CH3 at C8), 1.65–1.59
(m, 2 H, H3, H4), 1.50–1.43 (m, 1 H, H4), 1.35–1.31 (m, 1 H, H3), 1.15
(s, 3 H, CH3 at C6), 0.86 (s, 3 H, CH3 at C6), 0.84 (d, J = 7.2 Hz, 3 H, CH3
at C2).
13C NMR (75 MHz, CDCl3): δ = 219.3 (C11), 138.2 (C8), 120.6 (C9), 65.8
(C7), 60.2 (C1), 57.2 (C5), 42.3 (C6), 41.9 (C10), 36.1 (C3), 33.7 (C2),
25.9 (CH3 at C6), 24.6 (C4 and CH3 at C6), 24.3 (CH3 at C8), 15.1 (CH3 at
C2).
8a
Rf = 0.39 (cHex/EtOAc 50:1).
[α]λ20 +36.8 (365 nm), +24.2 (436 nm), +11.0 (546 nm), +9.1 (579 nm),
+8.1 (589 nm) (c = 0.65 g/100 ml in CH2Cl2).
(–)-(α)-Cedrene (1)
IR (ATR): 2951 (vs), 2868 (m), 1458 (m), 1447 (m), 1375 (m), 1131
(m), 1038 (m), 751 cm–1 (m).
Cedrenone (9; 50 mg, 0.23 mmol, 1.0 equiv) and tosylhydrazine (53
mg, 0.26 mmol, 1.3 equiv) were dissolved in EtOH (2 mL) and refluxed
for 2.5 h. The solvent was evaporated and the residue was dissolved in
THF/H2O (4:1, 5 mL). NaBH4 (35 mg, 0.92 mmol, 4.0 equiv) was slowly
added and the mixture was refluxed again for 2 h. After cooling down
to r.t., the mixture was diluted with H2O and n-pentane and the layers
were separated. The aqueous layer was extracted with n-pentane (3
×). The combined organic layers were washed first with sat. aq
NaHCO3, then with aq 1 N HCl and brine, and finally dried (MgSO4).
After evaporating the solvent, the residue was subjected to column
chromatography (n-pentane) to yield (–)-α-cedrene (1) as a colorless
liquid (43 mg, 0.22 mmol, 92%).
1H NMR (500 MHz, CDCl3): δ = 5.57 (d, J = 5.6 Hz, 1 H, H10), 5.54 (d, J =
5.6 Hz, 1 H, H9), 3.35 (s, 3 H, OCH3), 2.44–2.39 (m, 1 H, H2), 2.06–2.01
(m, 1 H, H3a), 1.87–1.84 (m, 1 H, H5), 1.62 (s, 1 H, H7), 1.55–1.49 (m,
2 H, H4), 1.32 (s, 3 H, CH3 at C8), 1.11–1.08 (m, 1 H, H3b), 1.03 (d, J =
7.2 Hz, 3 H, CH3 at C2), 1.00 (s, 3 H, CH3 at C6), 0.99 (s, 3 H, CH3 at C6).
13C NMR (126 MHz, CDCl3): δ = 134.5 (C10), 131.7 (C9), 94.8 (C8), 72.9
(C11), 68.6 (C5), 57.7 (OCH3), 56.1 (C7), 42.7 (C1), 40.8 (C6), 37.7 (C3),
32.5 (C2), 29.0 (2 × CH3 at C6), 28.4 (C4), 18.7 (CH3 at C2), 17.3 (CH3 at
C8).
GC-MS (70 eV): m/z (%) = 232 (7, [M]+), 217 (8, [M – CH3]+), 149 (100),
20
133 (15), 115 (28), 91 (48).
[α]λ –330.5 (365 nm), –195.8 (436 nm), –109 (546 nm), –94.7 (579
nm), –91.2 (589 nm) (c = 0.57 g/100 mL in CH2Cl2).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G