6
Tetrahedron
1
1590, 1540, 1454, 1166, 1034, 839, 765 cm-1; H NMR (300
127.9, 127.4 (2C), 126.4, 85.5, 30.7, 26.4. HRMS (EI): m/z calcd
for C19H14O3 [M]+ 290.0946, found 290.0943. HPLC: Chiralcel®
OD-H, Hexane/i-PrOH (85:15), flow rate: 1.0 mL/min, λ = 254
nm, tR1(minor) = 15.5 min, tR2(major) = 21.4 min, ee = 10%. All
spectral and physical characteristics of spirolactone 2f are
consistent with those reported in the literature.4b
ACCEPTED MANUSCRIPT
MHz, CDCl3) δ 8.01 (d, J = 7.5 Hz, 1H), 7.77 – 7.69 (m, 2H),
7.55 – 7.41 (m, 1H), 6.66 (s, 1H), 2.87 (ddd, J = 17.6, 11.1, 9.6
Hz, 1H), 2.60 (ddd, J = 17.6, 9.6, 2.3 Hz, 1H), 2.45 (ddd, J =
13.5, 9.6, 2.3 Hz, 1H), 2.24 (ddd, J = 13.5, 11.1, 9.6 Hz, 1H); 13
C
NMR (75 MHz, CDCl3) δ 194.9, 175.8, 136.0, 135.2, 133.6,
130.2, 128.9, 128.1, 127.5, 122.6, 84.3, 31.3, 26.6. HRMS (EI):
m/z calcd for C13H9BrO3 [M]+ 291.9735, found 291.9746.
HPLC: Chiralcel® OD-H, Hexane/i-PrOH (85:15), flow rate: 1.0
mL/min, λ = 254 nm, tR1(minor) = 15.2 min, tR2(major) = 18.5
min, ee = 38%. All spectral and physical characteristics of
spirolactone 2c are consistent with those reported in the
literature.7b,d,15
Arnottin II (2g)
To a stirred suspension of arnottin I (8, 6.0 mg, 0.017 mmol) in
THF (0.6 mL) and MeOH (0.6 mL) were successively added
water (0.2 mL) and lithium hydroxide monohydrate (10.7 mg,
0.255 mmol) at room temperature. The reaction mixture was
heated to 60 °C and stirred overnight, after which time the
saponification was assumed to be complete. The resulting red
mixture was then cooled down to 0 °C, and diluted with a pre-
cooled aqueous solution of citric acid (50 mg in 1 mL) until the
solution became yellow (pH ≈ 3). Crushed ice was then added
into the separating funnel to maintain the temperature near 0 °C
during this work-up procedure, and the solution was extracted
with Et2O (3 × 1 mL). The combined organic extracts were dried
over Na2SO4, and evaporated to dryness while maintaining the
temperature below 10 °C. The resulting orangish residue was
immediately dissolved in CH2Cl2 (0.4 mL), and cesium
bicarbonate (16.5 mg, 0.085 mmol), water (0.8 mL) and the
phase-transfer agent 7e (10.4 mg, 0.017 mmol) were successively
added to the solution at room temperature. The resulting biphasic
solution was stirred at room temperature for 15 min before
cooling it down to 0 °C, whereafter a solution of BTI (8 mg,
0.019 mmol) in CH2Cl2 (0.4 mL) was added dropwise over 1 h
using a syringe pump. The reaction mixture was then stirred for 2
h, after which time a solution composed of 0.1 mL of saturated
aqueous sodium thiosulfate, 0.1 mL of saturated aqueous sodium
bicarbonate, and 1 mL of water was added. The organic layer was
separated and the aqueous layer was extracted with CH2Cl2 (3 × 2
mL). The combined organic extracts were washed with brine (2
mL), dried over Na2SO4, and evaporated to dryness. Purification
by column chromatography on silica gel, eluting with a
cyclohexane/EtOAc mixture (90:10 to 60:40), afforded recovered
arnottin I (2.5 mg) and arnottin II (2g, 2.0 mg, 32%, 54% brsm)
1',5-Dioxo-4,5-dihydro-1'H,3H-spiro[furan-2,2'-naphthalene]-4'-
carbaldehyde (spirolactone 2d)
This spirolactone was synthesized from naphthol 1d (24.4 mg,
0.1 mmol) and was obtained as a white solid (24.0 mg, 99%); Rf
= 0.26 (silica gel, EtOAc/cyclohexane 40:60); m.p. 169-171 °C;
IR (neat): 3059, 3030, 2944, 2920, 2872, 2850, 1786, 1693,
1591, 1278, 1175, 1032, 778, 703 cm-1; H NMR (300 MHz,
1
CDCl3) δ 9.82 (s, 1H), 8.65 (d, J = 7.8 Hz, 1H), 8.10 (dd, J = 7.6,
1.4 Hz, 1H), 7.73 (td, J = 7.8, 1.4 Hz, 1H), 7.53 (td, J = 7.6, 1.0
Hz, 1H), 7.01 (s, 1H), 2.90 (ddd, J = 17.6, 11.5, 9.4 Hz, 1H), 2.65
(ddd, J = 17.6, 9.4, 2.1 Hz, 1H), 2.49 (ddd, J = 13.4, 9.4, 2.1 Hz,
1H), 2.31 (ddd, J = 13.4, 11.5, 9.4 Hz, 1H). 13C NMR (75 MHz,
CDCl3): δ 194.6, 191.2, 175.5, 150.3, 136.0, 134.7, 132.3, 130.3,
128.7, 127.2, 127.1, 83.5, 31.2, 26.1. HRMS (ESI): m/z calcd for
C14H9O4 [M–H]- 241.0506, found 241.0502. HPLC: Chiralpak®
IA, Hexane/CHCl3 (70:30 to 35:65 over 60min), flow rate: 1.0
mL/min, λ = 254 nm, tR1(major) = 27.6 min, tR2(minor) = 35.5
min, ee = 34%.
4'-Phenyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-
1',5-dione (spirolactone 2e)
This spirolactone was synthesized from naphthol 1e4b,7b (29.2 mg,
0.1 mmol) and was obtained as a white solid (24.1 mg, 83%). Rf
= 0.22 (silica gel, EtOAc/cyclohexane 20:80); m.p. 172–174 °C.
(lit.4b 172-174 °C. IR (neat): 3564, 3060, 1784, 1693, 1591, 1175,
777, 703 cm-1; H NMR (300 MHz, CDCl3) δ 8.08 (dd, J = 7.7,
1
isolated as
a
yellow solid. Rf
=
0.46 (silica gel,
EtOAc/cyclohexane 50:50); m.p. 222-223 °C (lit.14 225-226 °C);
IR (neat): 2954, 2922, 2852, 1769, 1679, 1599, 1496, 1481,
1392, 1270, 1032, 1020, 932 cm-1; 1H NMR (600 MHz, CDCl3) δ
7.38 (s, 1H), 7.05 (d, J = 8.3 Hz, 1H), 6.78 (d, J = 8.3 Hz, 1H),
6.78 (s, 1H), 6.69 (d, J = 9.8 Hz, 1H), 6.10 (d, J = 1.2 Hz, 1H),
6.09 (d, J = 1.2 Hz, 1H), 6.09 (d, J = 9.8 Hz, 1H), 4.17 (s, 3H),
3.86 (s, 3H). 13C NMR (151 MHz, CDCl3): δ 191.1, 167.6, 154.1,
153.6, 149.2, 148.6, 139.3, 134.6, 130.4, 128.4, 123.2, 119.3,
117.4, 115.6, 108.1, 107.8, 102.6, 84.5, 62.9, 57.1. HRMS (ESI):
m/z calcd for C20H14O7Na [M+Na] 389.0631, found 389.0624.
HPLC: Chiralpak® IA, Hexane/i-PrOH/CHCl3 (63:16:21), flow
rate: 0.5 mL/min, λ = 254 nm, tR1(minor) = 15.2 min, tR2(major) =
19.1 min, ee = 0%. All spectral and physical characteristics of
arnottin II (2h) are identical to those reported in the literature.13b,c
1.2 Hz, 1H), 7.55 (td, J = 7.7, 1.5 Hz, 1H), 7.49 – 7.38 (m, 4H),
7.37 – 7.32 (m, 2H), 7.15 (d, J = 7.8 Hz, 1H), 6.12 (s, 1H), 2.91
(ddd, J = 17.6, 11.3, 9.5 Hz, 1H), 2.62 (ddd, J = 17.6, 9.5, 2.2 Hz,
1H), 2.52 (ddd, J = 13.4, 9.5, 2.2 Hz, 1H), 2.28 (ddd, J = 13.4,
11.3, 9.5 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 196.6, 176.5,
139.9, 137.7, 137.5, 135.4, 130.7, 129.0, 128.8 (2C), 128.7 (2C),
128.5, 128.2, 127.7, 127.5, 83.8, 31.6, 26.8. HRMS (EI): m/z
calcd for C19H14O3 [M]+ 290.0943, found 290.0944. HPLC:
Chiralcel® OD-H, Hexane/i-PrOH (85:15), flow rate: 1.0
mL/min, λ = 254 nm, tR1(major) = 16.6 min, tR2(minor) = 22.1
min, ee = 4%. All spectral and physical characteristics of
spirolactone 2e are consistent with those reported in the
literature.4b,7b
3'-Phenyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-
1',5-dione (spirolactone 2f)
Acknowledgments
This spirolactone was synthesized from naphthol 1f (29.2 mg, 0.1
mmol) and was obtained as a sticky yellow solid (22.9 mg, 79%).
Rf = 0.57 (silica gel, EtOAc/cyclohexane 40:60); m.p. 168–170
°C. (lit.4b 172-173 °C); IR (neat): 3557, 3056, 3960, 1789, 1687,
1596, 1289, 1171, 1030, 767 cm-1; 1H NMR (300 MHz, CDCl3) δ
8.03 (d, J = 7.7 Hz, 1H), 7.65 (td, J = 7.7, 1.4 Hz, 1H), 7.53 –
7.45 (m, 2H), 7.42 (dd, J = 7.6, 1.2 Hz, 1H), 7.40 – 7.36 (m, 3H),
7.31 (d, J = 7.6 Hz, 1H), 6.68 (s, 1H), 2.87 – 2.69 (m, 1H), 2.43 –
2.13 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 196.6, 176.6, 143.3,
137.3, 136.7, 135.9, 129.3, 128.9, 128.8, 128.6 (2C), 128.4,
Financial support from the Ministère de la Recherche and the
CNRS, including a ministerial research assistantship for K.A., is
gratefully acknowledged. We thank Simafex (France) for
providing us with the hypervalent iodine reagents used in this
study, Aladin Hamoud and Bastian Muriel for their initial
contributions to this work.