Synthesis of Sesquiterpenes
MEMCl (2.91 mL, 25.1 mmol) was slowly added dropwise. After
about 2 h, the greenish colour disappeared, and NaH (60% in min-
eral oil; 1.01 g, 25.3 mmol) was added. After 15 min, MEMCl
(3.34 mL, 28.78 mmol) was added dropwise. The reaction was
quenched after 2 h by the addition of saturated NH4Cl solution
(100 mL), and the mixture was extracted with EtOAc (3ϫ 70 mL).
The combined organic extracts were successively washed with
HB), 5.09 (d, J = 5.4 Hz, 1 H, 1ЈЈ-HA), 5.04 (d, J = 5.4 Hz, 1 H,
1ЈЈ-HB), 3.81 (m, 2 H, 2ЈЈ-H), 3.76 (m, 2 H, 6ЈЈ-H), 3.76 (s, 3 H,
3Ј-OCH3), 3.51 (m, 2 H, 7ЈЈ-H), 3.49 (m, 2 H, 3ЈЈ-H), 3.32 (s, 3 H,
8ЈЈ-H), 3.31 (s, 3 H, 4ЈЈ-H), 3.05 (d, J = 4.2 Hz, 1 H, 9-H), 2.12
(m, 1 H, 8-H), 1.94 (m, 1 H, 1-Heq), 1.62 (m, 1 H, 2-Hax), 1.56 (m,
2 H, 7-H), 1.43 (m, 2 H, 6-H), 1.33 (m, 1 H, 3-Heq), 1.31 (m, 1 H,
2-Heq), 1.23 (s, 3 H, 15-H), 1.12 (m, 1 H, 3-Hax), 0.96 (m, 1 H, 1-
NaHCO3 solution (2ϫ 50 mL), H2O (2ϫ 50 mL), and saturated Hax), 0.94 (d, J = 7.5 Hz, 3 H, 12-H), 0.81 (dd, J = 10.3, 2.3 Hz, 1
NaCl solution (2ϫ 50 mL), and passed through a plug of silica/
MgSO4, and the solvents were evaporated. The crude product was
purified by flash chromatography (silica gel; hexanes/Me2CO, 18:7)
H, 5-H), 0.79 (s, 6 H, 13-H, 14-H) ppm. 13C NMR (125 MHz,
CDCl3, 25 °C): δ = 206.2 (C-11), 153.8 (C-5Ј), 153.0 (C-3Ј), 137.9
(C-1Ј), 136.9 (C-2Ј), 106.5 (C-6Ј), 103.0 (C-4Ј), 98.6 (C-1ЈЈ), 93.8
(C-5ЈЈ), 71.5 (C-3ЈЈ), 71.4 (C-7ЈЈ), 69.2 (C-2ЈЈ), 67.5 (C-6ЈЈ), 64.8
to give 7 (7.20 g, 18.2 mmol, 80%) as a colourless viscous oil. Rf =
1
0.26 (hexanes/Me2CO, 18:7). H NMR (300 MHz, CDCl3, 25 °C): (C-9), 58.8 (C-4ЈЈ, C-8ЈЈ), 55.7 (3Ј-OCH3), 56.0 (C-5), 42.0 (C-3),
δ = 6.81 (d, J = 2.7 Hz, 1 H, 6-H), 6.54 (d, J = 2.7 Hz, 1 H, 4-H),
39.0 (C-1), 38.1 (C-10), 34.1 (C-7), 33.4 (C-13), 33.1 (C-4), 30.4 (C-
5.14 (s, 2 H, 5Ј-H), 5.11 (s, 2 H, 1Ј-H), 3.98 (m, 2 H, 2Ј-H), 3.75 8), 21.5 (C-14), 18.0 (C-2), 17.3 (C-6), 17.1 (C-12), 16.5 (C-15) ppm.
(m, 2 H, 6Ј-H), 3.74 (s, 3 H, OCH3), 3.54 (m, 2 H, 3Ј-H), 3.51 (m,
MS (EI, 70 eV): m/z (%) = 536 (20) [M]+, 460 (6), 447 (22), 372
2 H, 7Ј-H), 3.33 (s, 6 H, 4Ј-H, 8Ј-H) ppm. 13C NMR (75 MHz, (11), 316 (15), 255 (31), 240 (14), 193 (24), 137 (15), 123 (21), 89
CDCl3, 25 °C): δ = 154.1 (C-5), 153.6 (C-3), 138.0 (C-2), 117.5 (C- (100), 59 (100). HRMS (ESI): calcd. for C30H48O8Na [M + Na]+
1), 111.6 (C-6), 101.3 (C-4), 100.3 (C-1Ј), 93.7 (C-5Ј), 71.6 (C-3Ј),
71.4 (C-7Ј), 69.0 (C-2Ј), 67.5 (C-6Ј), 58.8 (C-4Ј, C-8Ј), 55.8 (OCH3)
ppm. MS (EI, 70 eV): m/z (%) = 396 (1) [M(81Br)]+, 394 (1)
[M(79Br)]+, 308 (1), 306 (1), 220 (2), 218 (3), 89 (78), 59 (100).
HRMS (ESI): calcd. for C15H23O7BrNa [M + Na]+ 417.0525;
found 417.0509.
559.3247; found 559.3230.
11-{3Ј-Methoxy-2Ј,5Ј-bis[(2ЈЈ-methoxyethoxy)methoxy]phenyl}-
driman-11-ol (20): LiEt3BH (1 m in THF; 5.70 mL, 5.70 mmol) was
added to a solution of (–)-drimanophenone 5 (608 mg, 1.14 mmol)
in absolute Et2O (100 mL) at 0 °C under an inert gas atmosphere.
After 2 h, half-saturated NH4Cl solution (50 mL) was added, and
the aqueous layer was extracted with MTBE (3ϫ 20 mL). The
combined organic extracts were passed through a plug of silica/
MgSO4, and the solvents were evaporated. The residue was purified
by column chromatography (hexanes/Me2CO, 3:1) to give benzylic
alcohol 20 (602 mg, 1.12 mmol, 98%) as a colourless oil. Rf = 0.28
(hexanes/Me2CO, 3:1). 1H NMR (500 MHz, CDCl3, 25 °C): δ =
6.64 (d, J = 2.8 Hz, 1 H, 6Ј-H), 6.52 (d, J = 2.8 Hz, 1 H, 4Ј-H),
5.23 (d, J = 6.8 Hz, 1 H, 5ЈЈ-HA), 5.18 (d, J = 8.0 Hz, 1 H, 11-H),
5.18 (d, J = 6.8 Hz, 1 H, 5ЈЈ-HB), 5.13 (s, 2 H, 1ЈЈ-H), 4.01 (m, 1
H, 2ЈЈ-HA), 3.79 (m, 2 H, 6ЈЈ-H), 3.78 (s, 3 H, 3Ј-OCH3), 3.77 (m,
1 H, 2ЈЈ-HB), 3.55 (m, 4 H, 7ЈЈ-H, 3ЈЈ-H), 3.37 (s, 3 H, 8ЈЈ-H[a]),
3.33 (s, 3 H, 4ЈЈ-H[a]), 1.73 (dd, J = 9.6 Hz, 3.8 Hz, 1 H, 9-H), 1.58
(m, 1 H, 2-Hax), 1.50 (m, 1 H, H-8), 1.43 (m, 1 H, 6-Heq), 1.40 (m,
2 H, 7-H), 1.37 (m, 1 H, 2-Heq), 1.34 (m, 1 H, 3-Heq), 1.33 (m, 1
H, 6-Hax), 1.28 (m, 1 H, 1-Heq), 1.21 (m, 2 H, 1-Hax, 3-Hax), 1.10
(s, 3 H, 15-H), 0.94 (dd, J = 10.3 Hz, 2.3 Hz, 1 H, 5-H), 0.84 (s, 3
H, 13-H), 0.82 (s, 3 H, 14-H), 0.71 (d, J = 7.3 Hz, 3 H, 12-H) ppm.
[a] assignments may be reversed. 13C NMR (125 MHz, CDCl3,
25 °C): δ = 154.1 (C-5Ј), 152.1 (C-3Ј), 139.6 (C-1Ј), 138.2 (C-2Ј),
107.1 (C-6Ј), 100.4 (C-4Ј), 98.0 (C-1ЈЈ), 93.8 (C-5ЈЈ), 71.7 (C-3ЈЈ[b]),
71.6 (C-7ЈЈ[b]), 69.7 (C-11), 69.3 (C-2ЈЈ), 67.5 (C-6ЈЈ), 59.0 (C-4ЈЈ[c]),
58.9 (C-8ЈЈ[c]), 57.2 (C-9), 56.8 (C-5), 55.7 (3Ј-OCH3), 42.1 (C-3),
41.5 (C-1), 40.0 (C-10), 35.2 (C-7), 33.9 (C-13), 33.5 (C-4), 30.7 (C-
8), 21.7 (C-14), 18.6 (C-2), 17.4 (C-6), 17.2 (C-15), 16.3 (C-12) ppm.
[b, c] assignments may be reversed. MS (EI, 70 eV): m/z (%) = 538
(5) [M]+, 435 (95), 355 (7), 294 (28), 269 (57), 205 (26), 191 (16),
89 (100), 59 (100). HRMS (ESI): calcd. for C30H50O8Na [M +
Na]+ 561.3403; found 561.3398.
Drimanoyl Chloride (19): (+)-Drimanic acid (2; 866 mg, 3.63 mmol)
was dissolved in absolute CH2Cl2 (45 mL) under an inert gas atmo-
sphere, and oxalyl chloride (3.12 mL, 36.3 mmol) and DMF (2 μL,
26 μmol) were added. After 20 min, the evolution of gas ended, and
the reaction mixture was stirred for a further 30 min. The volatile
compounds were removed at 40 °C and 7 mbar to give 19 (933 mg,
3.63 mmol, 100%) pale yellowish waxy solid. 1H NMR (300 MHz,
CDCl3, 25 °C): δ = 2.79 (d, J = 4.7 Hz, 1 H, 9-H), 2.67 (m, 1 H,
8-H), 1.86 (m, 1 H, 1-Heq), 1.72 (m, 2 H, 7-H), 1.62 (m, 1 H, 2-
Hax), 1.51 (m, 1 H, 6-Heq), 1.41 (m, 2 H, 6-Hax, 2-Heq), 1.39 (m, 1
H, 3-Heq), 1.19 (s, 3 H, 15-H), 1.16 (m, 1 H, 3-Hax), 1.10 (d, J =
7.4 Hz, 3 H, 12-H), 1.05 (m, 1 H, 1-Hax), 0.90 (s, 3 H, 13-H), 0.82
(s, 3 H, 14-H), 0.78 (dd, J = 10.6, 3.5 Hz, 1 H, 5-H) ppm. 13C
NMR (75 MHz, CDCl3, 25 °C): δ = 173.4 (C-11), 73.0 (C-9), 55.3
(C-5), 41.8 (C-3), 39.4 (C-1), 39.2 (C-10), 33.4 (C-7, C-13), 33.1 (C-
4), 30.8 (C-8), 21.5 (C-14), 17.9 (C-2), 17.1 (C-6), 16.9 (C-12), 16.3
(C-15) ppm.
(–)-11-{3Ј-Methoxy-2Ј,5Ј-bis[(2ЈЈ-methoxyethoxy)methoxy]-
phenyl}driman-11-one (5): Compound 7 (2.15 g, 5.44 mmol) was
dissolved in Et2O (17 mL) in a Schlenk flask equipped with an
SmCo magnetic stirrer bar under an inert gas atmosphere, and the
solution was cooled to –78 °C. nBuLi (2.1 m in hexanes; 2.54 mL,
5.27 mmol) was added over 5 min with vigorous stirring. The re-
sulting highly viscous white suspension was stirred vigorously for
a further 10 min. Then, a freshly prepared solution of drimanoyl
chloride 19 (933 mg, 3.63 mmol) in absolute Et2O (13 mL) was
added, and the flask was rinsed with absolute Et2O (2ϫ 3 mL).
After 5 min, the cooling bath was removed, and the reaction mix-
ture was stirred at room temp. for 1.5 h. The mixture was then
partitioned between MTBE (100 mL) and half-saturated NH4Cl
solution (50 mL). The aqueous layer was extracted with MTBE
(2ϫ 50 mL). The combined organic extracts were passed through
a plug of silica/MgSO4, and the solvents were evaporated. The pale
yellowish crude product was purified by flash chromatography
(hexanes/Me2CO, 3:1) to give 5 (1.24 g, 2.33 mmol, 64 %) as a
Deoxyspongiaquinol (3): Benzylic alcohol 20 (306 mg, 568 μmol)
was dissolved in benzene (20 mL) under an inert gas atmosphere,
and SO3·pyridine (118 mg, 741 μmol) was added. The reaction mix-
ture was heated under reflux for 2.5 h. Then it was cooled to room
temp., and filtered through a plug of silica, which was rinsed with
EtOAc (250 mL). The solvent was evaporated.
colourless viscous oil. Rf = 0.32 (hexanes/Me2CO, 3:1). [α]2D3
–17.3 (c = 1.7, CHCl3). H NMR (500 MHz, CDCl3, 25 °C): δ = (20 mL) under an inert gas atmosphere and HCl (2 m in absolute
6.64 (d, J = 2.8 Hz, 1 H, 4Ј-H), 6.50 (d, J = 2.8 Hz, 1 H, 6Ј-H), Et2O; 5 mL) was added. After 2.5 h, half-saturated NaHCO3 solu-
5.18 (d, J = 7.0 Hz, 1 H, 5ЈЈ-HA), 5.15 (d, J = 7.0 Hz, 1 H, 5ЈЈ- tion (20 mL) was added, and the reaction mixture was partitioned
=
The elimination product (320 mg) was dissolved in absolute EtOH
1
Eur. J. Org. Chem. 2014, 6975–6982
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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