The Journal of Organic Chemistry
Article
silica gel 60 F254 plates, and visualization was accomplished by UV
light. Column chromatography was performed on silica gel (Aldrich
toluene until all of the green component was collected). After removal
of the solvent, the crude thioketone was purified by column
chromatography on silica using n-pentane/toluene 7:1 as the eluent.
Product 12 was collected as a dark-blue liquid (327 mg) in 50% yield
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60, 230−400 mesh). H NMR spectra were recorded on 400 or 500
MHz NMR spectrometers. 13C NMR spectra were recorded on 100 or
1
125 MHz NMR spectrometers. Chemical shifts (δ) are denoted in
and stored at −24 °C under an argon atmosphere. H NMR (400
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parts per million relative to CDCl3 (for H detection, δ = 7.26 ppm;
MHz, CDCl3): δ 7.21 (d, J = 7.5 Hz, 1H), 7.01 (d, J = 7.5 Hz, 1H),
3.04 (s, 3H), 2.68 (s, 3H), 2.35 (s, 3H), 0.97 (s, 9H). 13C NMR (100
MHz, CDCl3): δ 250.1, 152.9, 145.0, 136.6, 133.5, 132.0, 130.7, 71.2,
35.3, 33.1, 28.0, 21.7, 18.2. HRMS (ESI) m/z: calcd for C15H21S+
233.13640 [M + H]+, found 233.13602 [M + H]+.
1
for 13C detection, δ = 77.16 ppm) or CD2Cl2 (for H detection, δ =
5.32 ppm; for 13C detection, δ = 53.50 ppm). For 1H NMR
spectroscopy, the splitting pattern of peaks is designated as follows: s
(singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br
(broad), or dd (doublet of doublets). HRMS spectra were obtained on
an LTQ Orbitrap XL mass spectrometer with ESI, APCI, or APPI
ionization. Cryo-UV−vis and CD measurements were performed using
a variable-temperature liquid nitrogen cryostat inserted into an FT
spectrophotometer or a spectropolarimeter. Transient absorption
experiments were performed using a Nd:YAG laser (FWHM, 8 ns;
355/532/1064 nm; up to 600 mW), a xenon lamp (250−800 nm,
using a 200−2500 nm monochromator with an accuracy of 0.2 nm),
and a 185−900 nm PMT detector. Irradiation experiments with UV
light were performed using an ENB-280C/FE lamp with λ = 312 30
or 365 30 nm or a 200 W Hg lamp fitted with suitable bandpass
filters (typical bandwidth of 10 nm). Irradiation experiments with
visible light were performed using suitable cutoff filters.
Dispiro[9H-fluorene-9,2′-thiirane-3′,1″-(2″-tert-butyl-4″,7″-di-
methyl-2″,3″-dihydro-1H-indene)] (16). Thioketone 12 (50 mg, 0.22
mmol) and diazofluorenone (15) (83 mg, 0.44 mmol) were dissolved
in dry toluene (20 mL) under a nitrogen atmosphere, and the mixture
was stirred at 70 °C for 1 h. The temperature of the solution was
slowly increased until reflux. The reaction ran overnight at reflux and
was followed by TLC (n-pentane/AcOEt 300:1). Upon depletion of
the starting compounds 12 and 15, the solvent was evaporated. The
crude product was first purified by column chromatography on silica
with n-pentane/toluene 11:1 as the eluent and then by crystallization
from n-heptane. Episulfide 16 was obtained as a white solid (32 mg) in
1
38% yield. H NMR (500 MHz, CDCl3): δ 7.71 (d, J = 7.3 Hz, 1H),
7.62 (d, J = 7.5 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.39 (t, J = 7.0 Hz,
1H), 7.32 (t, J = 7.5 Hz, 1H), 7.18 (t, J = 7.2 Hz, 1H), 7.09 (d, J = 7.8
Hz, 1H), 6.95 (t, J = 7.6 Hz, 1H), 6.81 (d, J = 7.7 Hz, 1H), 6.77 (d, J =
7.7 Hz, 1H), 2.83 (s, 3H), 2.71 (d, J = 6.2 Hz, 1H), 2.42 (d, J = 15.7
Hz, 1H), 2.03 (dd, J = 15.7, 6.2 Hz, 1H), 1.97 (s, 3H), 0.87 (s, 9H).
13C NMR (125 MHz, CDCl3): δ 145.7, 144.3, 142.4, 141.2, 141.2,
139.1, 132.8, 130.4, 129.6, 128.9, 127.9, 127.6, 126.6, 126.2, 126.0,
124.4, 120.0, 119.6, 61.0, 56.3, 51.6, 34.6, 31.6, 29.2, 20.9, 18.2. HRMS
(ESI) m/z: calcd for C28H29S+ 397.19900 [M + H]+, found 397.19827
[M + H]+.
Syntheses. (4,7-Dimethyl-1H-inden-3-yloxy)trimethylsilane (10).
To a stirred solution of ketone 930,31 (3.0 g, 19 mmol) and Et3N (8.0
mL, 57 mmol) in benzene (60 mL) under a nitrogen atmosphere was
added TMSOTf (8.0 mL, 46 mmol), and the resulting mixture was
stirred overnight at room temperature. The progress of the reaction
was followed by TLC (n-pentane/AcOEt 30:1), but care had to be
taken as the product decomposed on silica. The reaction was
quenched by the addition of a saturated aqueous NaHCO3 solution
(50 mL). The organic layer was separated, and the aqueous layer was
washed with n-pentane (3 × 20 mL). The combined organic layers
were dried on anhydrous Na2SO4. After filtration, the solvent was
evaporated to afford a brown liquid that solidified upon standing. A 1H
NMR spectrum of the crude intermediate showed the complete
conversion of ketone 9 into intermediate 10, which was used in the
next step without further purification. 1H NMR (400 MHz, CDCl3): δ
7.04 (d, J = 7.6 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 5.47 (t, J = 1.8 Hz,
1H), 3.19 (d, J = 1.8 Hz, 2H), 2.65 (s, 3H), 2.38 (s, 3H), 0.40 (s, 9H).
13C NMR (100 MHz, CDCl3): δ 155.7, 142.0, 138.4, 130.4, 129.1,
128.7, 126.5, 105.3, 32.7, 18.0, 17.7, 0.2.
9-(2-tert-Butyl-4,7-dimethyl-2,3-dihydro-1H-inden-1-ylidene)-9H-
fluorene (7). Episulfide 16 (32 mg, 0.08 mmol) was dissolved along
with P(C6H5-OMe-p)3 (35 mg, 0.10 mmol) in dry toluene (10 mL),
and the stirred mixture was heated at reflux overnight under a nitrogen
atmosphere. The solvent was evaporated, and the crude product was
purified by column chromatography on silica with n-pentane/AcOEt
300:1 as the eluent. Pure 7 was obtained as a white solid (27 mg) in
92% yield. The enantiomers of 7 were separated by preparative chiral
HPLC on an OD-H column with n-heptane/propane-2-ol 97:3 as the
eluent at a flux of 0.5 mL min−1. 1H NMR (500 MHz, CD2Cl2): δ 8.26
(dd, J = 5.5, 3.2 Hz, 1H), 7.83 (dd, J = 5.5, 3.2 Hz, 1H), 7.76 (d, J =
7.5 Hz, 1H), 7.47 (d, J = 7.9 Hz, 1H), 7.38 (dd, J = 5.7, 3.1 Hz, 2H),
7.30 (t, J = 7.4 Hz, 1H), 7.11 (m, 2H), 7.05 (d, J = 7.7 Hz, 1H), 4.22
(d, J = 5.6 Hz, 1H), 3.03 (dd, J = 15.0, 5.5 Hz, 1H), 2.86 (d, J = 15.0
Hz, 1H), 2.32 (s, 3H), 2.28 (s, 3H), 0.88 (s, 9H). 13C NMR (125
MHz, CD2Cl2): δ 152.2, 146.3, 142.6, 140.7, 139.8, 139.6, 138.5,
133.3, 130.9, 130.9, 130.4, 128.5, 127.5, 127.2, 126.9, 126.7, 125.4,
124.1, 119.8, 119.2, 58.6, 35.8, 35.5, 29.0, 20.7, 18.3. HRMS (ESI) m/
z: calcd for C28H29+ 365.22693 [M + H]+, found 365.22620 [M + H]+.
(E,Z)-Dispiro[2-methoxy-9H-fluorene-9,2′-thiirane-3′,1″-(2″-tert-
butyl-4″,7″-dimethyl-2″,3″-dihydro-1H-indene)] (E,Z-21). Thioke-
tone 12 (135 mg, 0.582 mmol) and diazofluorenone 20 (260 mg,
1.17 mmol) were dissolved in dry toluene (55 mL), and the mixture
was heated at reflux under a nitrogen atmosphere overnight. The
solvent was evaporated, and the crude product was purified by column
chromatography on silica with n-pentane/toluene 3:1 as the eluent.
Two fractions were collected, one containing predominantly one
diastereoisomer of 21 (57 mg) and the other one containing
predominantly the other diastereoisomer of 21 (110 mg). The crude
products were immediately used in the next step without further
purification. The overall crude yield of the reaction was 67%. HRMS
(ESI) m/z: calcd for C29H31OS+ 427.20956 [M + H]+, found
427.20904 [M + H]+.
2-tert-Butyl-4,7-dimethyl-2,3-dihydro-1H-inden-1-one (11).
Crude compound 10 (obtained from 19 mmol of ketone 9) was
dissolved in dry dichloromethane (24 mL), which was degassed with
argon, and 2.4 mL (21 mmol) of t-BuCl was added under an argon
atmosphere. The solution was cooled to −50 °C, and TiCl4 (2.4 mL,
21 mmol) was added in one portion. The reaction mixture was stirred
at that temperature, and the progress of the reaction was monitored by
TLC (n-pentane/AcOEt 30:1). After approximately 1 h, the reaction
was quenched by the addition of water (50 mL) and dichloromethane
(25 mL). The layers were separated, and the organic layer was washed
once more with water and once with diluted aqueous NaHCO3
solution. The organic solution was dried on anhydrous Na2SO4.
After filtration, the solvent was evaporated to afford a brown liquid
that was purified by column chromatography on silica using n-
pentane/AcOEt 30:1 as the eluent. This afforded ketone 11 as a waxy
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off-white solid (2.0 g) in 48% yield. H NMR (400 MHz, CDCl3): δ
7.22 (d, J = 7.4 Hz, 1H), 6.99 (d, J = 7.4 Hz, 1H), 3.02 (dd, J = 17.4,
8.1 Hz, 1H), 2.78 (dd, J = 17.4, 3.7 Hz, 1H), 2.58 (s, 3H), 2.44 (dd, J
= 7.7, 4.4 Hz, 1H), 2.31 (s, 3H), 1.06 (s, 9H). 13C NMR (100 MHz,
CDCl3): δ 209.5, 152.9, 135.9, 135.1, 134.3, 132.5, 129.4, 56.9, 33.9,
28.6, 27.8, 18.3, 17.6. HRMS (ESI) m/z: calcd for C15H21O+
217.15924 [M + H]+, found 217.15877 [M + H]+.
2-tert-Butyl-4,7-dimethyl-2,3-dihydro-1H-inden-1-thione (12).
Ketone 11 (614 mg, 2.84 mmol) was dissolved in dry toluene (60
mL), and P4S10 (14.0 g, 31.5 mmol) was added to the solution. The
reaction mixture was heated at reflux with stirring under a nitrogen
atmosphere. After 18 h the mixture was cooled to room temperature
and filtered over a plug of silica (the silica was flushed with more
(E,Z)-9-(2-tert-Butyl-4,7-dimethyl-2,3-dihydro-1H-inden-1-yli-
dene)-2-methoxy-9H-fluorene (E,Z-17). Episulfide 21 (first fraction;
57 mg, 0.13 mmol) and P(C6H5-OMe-p)3 (60 mg, 0.17 mmol) were
dissolved in dry toluene (20 mL), and the stirred mixture was heated
at reflux overnight under a nitrogen atmosphere in the absence of light.
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dx.doi.org/10.1021/jo500411z | J. Org. Chem. 2014, 79, 4446−4455