H
J. Lu et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3): = 6.39 (t, J = 5.6 Hz, 1 H, =CH), 3.99–3.85
(m, 4 H, 2 OCH2), 2.77 (dd, J = 15.6, 5.6 Hz, 1 H), 2.39 (t, J = 7.6 Hz, 2
H), 2.13 (s, 3 H, COCH3), 2.12–1.62 (m, 9 H), 1.58–1.16 (m, 10 H), 1.05
(s, 3 H, CH3), 0.95 (s, 3 H, CH3), 0.93 (s, 3 H, CH3), 0.89 (s, 6 H, 2 CH3),
0.85 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): = 209.4, 208.0, 137.1, 135.2, 113.2,
65.12, 65.11, 54.2, 53.1, 47.8, 44.6, 42.4, 41.7, 39.9, 38.0, 36.9, 35.9,
34.4, 30.2, 27.23, 27.19, 27.0, 26.8, 23.1, 20.1 (2 C), 19.1, 18.7, 18.3,
16.7.
13C NMR (100 MHz, CDCl3): = 202.7, 176.6, 118.1, 113.1, 65.08,
65.02, 59.7, 53.7, 44.0, 43.2, 42.3, 41.9, 39.3, 38.38, 38.35, 37.9, 37.1,
36.7, 33.5, 30.6, 28.0, 27.0, 24.2, 23.1, 22.0, 21.5, 20.7, 20.1, 18.6, 16.2.
MS (EI): m/z (%) = 477.4 (60) [M + Na]+.
HRMS-ESI: m/z [M + Na]+ calcd for C30H46NaO3: 477.3345; found:
477.3359.
Compound (+)-11 was crystallized from a mixture of diethyl ether
and hexane (1:1) to give single crystals and the structure was solved
by X-ray analysis.
MS (EI): m/z (%) = 495.3 (70) [M + Na]+.
HRMS-ESI: m/z [M + Na]+ calcd for C30H48NaO4: 495.3450; found:
495.3481.
(+)-(6a′R,8a′S,12a′R,12b′R,14b′R)-Ethyl 4′,4′,6a′,11′,11′,14b′-Hexa-
methyl-8′-oxo-2′,4′,4a′,5′,6′,6a′,8′,8a′,9′,10′,11′,12′,12a′,12b′,13′,14′,
14a′,14b′-octadecahydro-1′H-spiro[[1,3]dioxolane-2,3′-picene]-
8a′-carboxylate [(+)-5]
The product was crystallized from diethyl ether to give single crystals
and the structure was verified by X-ray analysis.
[LDA was prepared by following the procedure described in the syn-
thesis (–)-9 and was titrated prior to use]. To a cold (–78 °C) solution
of (–)-10 (0.173 g, 0.38 mmol) in THF (2 mL) under argon was added a
solution of LDA (0.57 mmol) in THF (1 mL) by syringe. The resulting
solution was stirred at –78 °C for 1 h, HMPA (0.102 g, 0.57 mmol) was
added and the mixture was stirred for 15 min. Next, ethyl cyanofor-
mate (75 mg, 0.76 mmol) was added and the mixture was stirred for
30 min. The reaction mixture was diluted with aqueous NH4Cl solu-
tion and extracted with ethyl acetate (3 × 20 mL). The combined or-
ganic layers were washed with water and brine, dried (MgSO4), con-
centrated, and column chromatographed on silica gel using a mixture
of hexane, dichloromethane and diethyl ether (8:3:1) as eluent to give
pure (+)-5.
(–)-(6a′R,8a′S,12a′R,12b′R,14b′R)-4′,4′,6a′,11′,11′,14b′-Hexamethyl-
4′,4a′,5′,6′,6a′,8a′,9′,10′,11′,12′,12a′,12b′,13′,14′,14a′,14b′-hexadeca-
hydro-1′H-spiro[[1,3]dioxolane-2,3′-picen]-8′(2′H)-one [(–)-10]
and (+)-(6a′R,8a′R,12a′S,12b′R,14b′R)-4′,4′,6a′,11′,11′,14b′-Hexam-
ethyl-4′,4a′,5′,6′,6a′,8a′,9′,10′,11′,12′,12a′,12b′,13′,14′,14a′,14b′-
hexadecahydro-1′H-spiro[[1,3]dioxolane-2,3′-picen]-8′(2′H)-one
[(+)-11]
To a solution of distilled ethanol (5 mL) under argon at 25 °C was add-
ed sodium (11 mg, 0.46 mmol) and the resulting solution was stirred
for 10 min until all the sodium metal had dissolved. To a solution of
(–)-6 (0.11 g, 0.23 mmol) in distilled ethanol (40 mL) under argon was
added the above sodium ethoxide solution via cannula. The resulting
yellow solution was stirred at 55 °C for 14 h, cooled to 25 °C, neutral-
ized with acetic acid, and concentrated under vacuum to remove eth-
anol and water. The residue was diluted with water and extracted
with ethyl acetate (3 × 30 mL). The combined organic layer washed
with water and brine, dried (MgSO4), concentrated, and column chro-
matographed on silica gel using a mixture of hexane, dichlorometh-
ane and diethyl ether (7.5:3:1) as eluent to give products (–)-10 and
(+)-11.
Yield: 90 mg (45%); white solid; mp 153–155 °C; []D25 = 91.3 (c
0.425, CHCl3).
1H NMR (400 MHz, CDCl3): = 5.79 (s, 1 H, =CH), 4.16–4.06 (m, 2 H,
CO2CH2), 3.95–3.84 (m, 4 H, 2 OCH2), 2.54 (dd, J = 12.8, 4.4 Hz, 1 H),
2.34 (ddd, J = 13.6, 7.2, 3.2 Hz, 1 H), 2.15 (dd, J = 13.6, 3.6 Hz, 1 H),
1.92 (d, J = 12.0 Hz, 1 H), 1.80 (td, J = 13.6, 3.2 Hz, 2 H), 1.71–1.57 (m,
5 H), 1.51–1.28 (m, 6 H), 1.24 (t, J = 7.6 Hz, 3 H, CH3CH2O2C), 1.18–
1.10 (m, 5 H), 1.08 (s, 3 H, CH3), 0.98 (s, 3 H, CH3), 0.94 (s, 3 H, CH3),
0.92 (s, 3 H, CH3), 0.85 (s, 3 H, CH3), 0.83 (s, 3 H, CH3).
Compound (–)-10 (Less Polar Product)
Yield: 45 mg (40%); white solid; mp 203.0–205.0 °C; []D25 = –34.0 (c
0.15, CHCl3).
1H NMR (400 MHz, CDCl3): = 5.81 (d, J = 2.0 Hz, 1 H, =CH), 3.98–3.87
(m, 4 H, 2 OCH2), 2.33–2.25 (m, 1 H), 2.17–2.09 (m 1 H), 2.02 (ddd,
J = 15.6, 8.4, 4.4 Hz, 1 H), 1.87–1.57 (m, 5 H), 1.52–1.29 (m, 9 H), 1.26–
1.09 (m, 6 H), 1.09 (s, 3 H, CH3), 0.94 (s, 3 H, CH3), 0.93 (s, 6 H, 2 CH3),
0.86 (s, 6 H, 2 CH3).
13C NMR (100 MHz, CDCl3): = 197.2, 174.6, 172.3, 117.8, 113.2, 65.2
(2 C), 61.4, 58.6, 55.6, 53.6, 43.6, 42.9, 42.4, 41.4, 39.5, 38.3, 38.1, 37.1,
34.96, 34.95, 32.9, 30.6, 27.5, 27.1, 24.6, 23.2, 22.0, 21.3, 20.2, 18.7,
16.4, 14.3.
MS (EI): m/z (%) = 549.4 (100) [M + Na]+.
HRMS-ESI: m/z [M + Na]+ calcd for C33H50NaO5: 549.3556; found:
549.3559.
The product was crystallized from a mixture of diethyl ether and hex-
ane (1:1) to give single crystals and the structure was solved by X-ray
analysis.
13C NMR (100 MHz, CDCl3): = 202.9, 174.7, 119.5, 113.2, 65.1 (2 C),
56.7, 53.3, 48.5, 44.4, 42.3, 41.2, 41.1, 40.5, 38.8, 38.1, 37.9, 37.0, 33.4,
32.8, 30.6, 27.1, 24.8, 23.1, 23.0, 21.5, 20.4, 20.1, 18.7, 16.6.
MS (EI): m/z (%) = 477.3 [M + Na]+.
HRMS-ESI: m/z [M + Na]+ calcd for C30H46NaO3: 477.3345; found:
(–)-(6a′R,8a′R,12a′S,12b′R,14b′R)-Ethyl 4′,4′,6a′,11′,11′,14b′-Hexa-
methyl-8′-oxo-2′,4′,4a′,5′,6′,6a′,8′,8a′,9′,10′,11′,12′,12a′,12b′,13′,14′,
14a′,14b′-octadecahydro-1′H-spiro[[1,3]dioxolane-2,3′-picene]-
8a′-carboxylate [(–)-4]
477.3360.
Compound (+)-11 (More Polar Product)
Yield: 35 mg (30%); white solid; mp 201.0–203.5 °C; []D25 = +222.5 (c
0.19, CHCl3).
1H NMR (400 MHz, CDCl3): = 5.75 (s, 1 H, =CH), 4.02–3.84 (m, 4 H, 2
OCH2), 2.37 (dt, J = 13.2, 4.4 Hz, 1 H), 2.09–1.61 (m, 6 H), 1.58–1.17
(m, 12 H), 1.14–0.98 (m, 4 H), 1.13 (s, 3 H, CH3), 0.94 (s, 9 H, 3 CH3),
0.87 (s, 3 H, CH3), 0.84 (s, 3 H, CH3).
To a cold (–78 °C) solution of (+)-11 (40 mg, 0.088 mmol) in dried di-
ethyl ether (1 mL) under argon was added freshly prepared LDA (0.12
mmol) in diethyl ether (1 mL), and the solution was stirred at –78 °C
for 1 h. HMPA (24 mg, 0.12 mmol) was added and the mixture was
stirred at –78 °C for 15 min. Next, ethyl cyanoformate (18 mg, 0.17
mmol) added and the mixture was for 30 min. The reaction mixture
was diluted with aqueous NH4Cl solution and extracted with ethyl ac-
etate (3 × 10 mL). The combined organic layers were washed with
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I