The Journal of Organic Chemistry
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would significantly decrease) to give an orange-yellow mixture, which
was stirred at −78 °C for 15 min. At this time, p-quinone monoketal 98
(297 mg, 0.60 mmol) was added in THF (1.80 mL, 0.33 M) dropwise
to the mixture. The resulting mixture was stirred at −78 °C and allowed
to slowly warm to room temperature. The color changed from orange
yellow to a deep purple, indicating formation of the deprotonated
anthraquinone. After 15 h, the purple mixture was cooled to 0 °C and
quenched with the addition of water. The mixture was transferred into a
separatory funnel with EtOAc (40 mL), and the layers were separated.
The aqueous layer was acidified with 1 N HCl to a pH of 4−5 and then
extracted with EtOAc (100 mL total). The red organic layer was dried
over Na2SO4, filtered, and concentrated to give a red residue. The
residue was purified by flash column chromatography (75% EtOAc/
hexanes) to give the desired anthraquinone 18 (250 mg, 66%) as a red
foam and the undesired epimer 100 (21 mg, 6%; total 72% yield of
anthraquinones) as a red solid, whose crystal structure was confirmed
by X-ray crystallography.18 If anthraquinone 100 was desired, the
reaction could be heated to reflux for 3 h or compound 18 could be
heated with > 1 equivalent t-BuOLi. Desired anthraquinone 18: TLC
(EtOAc): Rf 0.35 (UV, visible red spot). 1H NMR (400 MHz, CDCl3):
δ 12.90 (s, 1H), 7.85 (d, J = 1.0 Hz, 1H), 7.64 (t, J = 8.1 Hz, 1H), 7.36−
7.28 (m, 2H), 6.94 (s, 1H), 6.58 (s, 1H), 6.10−5.99 (m, 2H), 5.23 (s,
1H), 4.73 (d, J = 6.6 Hz, 1H), 4.63 (td, J = 6.9, 2.7 Hz, 1H), 4.00 (s,
3H), 3.93 (s, 3H), 3.90 (s, 3H), 3.08 (d, J = 14.2 Hz, 1H), 3.01 (d, J =
14.2 Hz, 1H), 2.55−2.40 (m, 1H), 2.35 (s, 2H), 2.32 (dd, J = 4.8, 2.7
Hz, 1H), 1.40 (s, 3H), 1.34 (s, 3H). 13C NMR (101 MHz, CDCl3): δ
189.1, 182.0, 168.3, 159.8, 158.2, 155.7, 152.3, 150.0, 147.3, 134.8,
134.7, 133.9, 129.4, 127.9, 127.8, 124.0, 120.5, 118.7, 118.6, 116.8,
114.7, 112.5, 111.8, 108.0, 81.0, 77.8, 72.1, 57.2, 56.7, 55.9, 46.5, 30.9,
29.8, 27.1, 25.2, 22.6. FTIR (ReactIR): 1761, 1670, 1607, 1237, 1048.
HRMS (ESI) m/z: [M + H]+ calc. for C36H35O10 627.2225, found
627.2254. [α]2D5 = −163° (c = 0.8, MeOH). Undesired epimer
anthraquinone 100: TLC (EtOAc): Rf 0.50 (UV, visible red spot). 1H
NMR (400 MHz, CDCl3): δ 13.34 (s, 1H), 7.91−7.85 (m, 2H), 7.66
(t, J = 8.1 Hz, 1H), 7.33 (dd, J = 8.5, 1.1 Hz, 1H), 7.24 (s, 1H), 6.73 (s,
1H), 5.74 (dt, J = 10.1, 4.1 Hz, 1H), 5.35 (s, 1H), 5.19 (dd, J = 10.1, 1.6
Hz, 1H), 4.18 (ddd, J = 7.7, 6.0, 3.8 Hz, 1H), 4.08 (dd, J = 6.0, 1.3 Hz,
1H), 4.01 (s, 3H), 3.97 (s, 3H), 3.96 (s, 3H), 3.58 (d, J = 13.8 Hz, 1H),
3.20 (d, J = 13.9 Hz, 1H), 2.46 (s, 4H), 2.12 (dtd, J = 18.5, 4.3, 2.0 Hz,
1H), 1.46 (s, 3H), 1.34 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 189.5,
182.1, 168.2, 159.8, 158.3, 156.3, 152.7, 150.5, 147.5, 134.6, 134.1,
133.8, 128.7, 128.2, 126.7, 123.9, 121.1, 118.9, 118.7, 116.8, 115.3,
112.0, 112.0, 107.4, 82.2, 75.4, 72.5, 57.5, 56.7, 56.0, 46.9, 33.1, 30.2,
27.8, 26.1, 22.9. FTIR (ReactIR): 1761, 1670, 1607, 1236, 1046.
HRMS (ESI) m/z: [M + H]+ calc. for C36H35O10 627.2225; found
627.2252. [α]2D5 = −1443° (c = 0.7, CHCl3).
CDCl3): δ 7.48 (dd, J = 7.9, 1.8 Hz, 2H), 7.28−7.22 (m, 3H), 7.08 (d, J
= 8.8 Hz, 1H), 6.86 (d, J = 8.9 Hz, 1H), 6.59 (s, 1H), 3.95 (s, 3H), 3.87
(s, 3H). 13C NMR (101 MHz, CDCl3): δ 167.1, 152.0, 147.8, 135.2,
134.3, 130.4, 129.0, 129.0, 118.1, 114.9, 113.3, 83.9, 56.5, 56.4. FTIR
(ReactIR): 1772, 1507, 1071, 1032, 967. LRMS (ESI): calculated [M +
H]+ 303.06, found 303.0.
New: Compound 106. Sulfide 105 (230 mg, 0.76 mmol) was
dissolved in CH2Cl2 (7.6 mL, 0.1 M) and cooled to 0 °C. One portion
of m-chloroperoxybenzoic acid (<77%, 341 mg, 1.52 mmol, 2 equiv)
was added at 0 °C. The mixture was stirred for 20 min at °C and then a
second portion of m-CPBA (170 mg, 0.76 mmol, 1 equiv) was added.
The mixture was stirred for 30 min afterward and then allowed to come
to room temperature and stirred for 1 h. The reaction was quenched
with aqueous saturated NaHCO3, and the layers were separated. The
organic layer was dried over Na2SO4, filtered, and concentrated. Further
purification by flash column chromatography (50% EtOAc/CH2Cl2)
gave the title sulfonated phthalide 106 as a white solid (188 mg, 0.56
mmol, 74%). 1H NMR (400 MHz, CDCl3): δ 7.93 (dd, J = 8.4, 1.3 Hz,
2H), 7.70−7.66 (m, 1H), 7.56 (dd, J = 8.4, 7.4 Hz, 2H), 7.22 (d, J = 8.9
Hz, 1H), 7.02 (d, J = 8.9 Hz, 1H), 6.23 (d, J = 0.5 Hz, 1H), 3.95 (s, 3H),
3.93 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 165.6, 152.6, 149.6,
135.9, 134.8, 130.0, 129.3, 128.5, 119.6, 115.1, 114.9, 89.6, 56.9, 56.6.
HRMS (ESI): calculated [M + H]+ 335.0584, found 335.0576. FTIR
(ReactIR): 1796, 1510, 1335, 1107, 1033.
New: Compounds 107 and 108. A flame-dried vial was charged
with t-BuOLi (1 M in THF, 1.06 mL, 2.65 equiv) and cooled to −78 °C.
Sulfone 106 (134 mg, 0.40 mmol, 1 equiv) was added as a solid in one
portion to give an orange-yellow mixture, which was stirred at −78 °C
for 15 min. At this time, p-quinone monoketal 98 (198 mg, 0.40 mmol)
was added in THF (1.21 mL, 0.33 M) dropwise to the mixture. The
resulting mixture was stirred at −78 °C and allowed to slowly warm to
room temperature. The color changed from orange yellow to a deep
purple, indicating formation of the deprotonated anthraquinone. After
15 h, the purple mixture was cooled to 0 °C and quenched with the
addition of water. The mixture was transferred into a separatory funnel
with EtOAc (40 mL), and the layers were separated. The aqueous layer
was acidified with 1 N HCl to a pH of 4−5 and then extracted with
EtOAc (100 mL total). The red organic layer was dried over Na2SO4,
filtered, and concentrated to give a red residue. The residue was purified
by flash column chromatography (90% EtOAc/hexanes) to give the
desired anthraquinone 107 (108 mg, 42%) as a red solid and the
undesired epimer 108 (36 mg, 14%; total 56% yield of anthraquinones)
as a red solid. Compound 107: 1H NMR: (400 MHz, CDCl3): δ 12.76
(s, 1H), 7.33−7.18 (m, 5H), 7.01 (s, 1H), 6.60 (s, 1H), 6.04−5.92 (m,
2H), 5.23 (s, 1H), 4.64 (d, J = 6.7 Hz, 1H), 4.58 (td, J = 6.9, 3.0 Hz,
1H), 3.97 (s, 3H), 3.94 (s, 3H), 3.91 (s, 3H), 3.90 (s, 3H), 3.10 (d, J =
14.1 Hz, 1H), 2.96 (d, J = 14.1 Hz, 1H), 2.49 (ddt, J = 17.7, 7.3, 2.4 Hz,
1H), 2.37 (s, 3H), 2.31 (dt, J = 17.9, 3.8 Hz, 1H), 1.38 (s, 3H), 1.31 (s,
3H). 13C NMR (101 MHz, CDCl3): δ 189.1, 182.8, 168.4, 158.2,
154.9, 154.2, 153.2, 151.2, 150.1, 147.3, 134.6, 129.7, 127.4, 126.6,
126.0, 121.8, 121.5, 120.7, 118.5, 117.1, 115.9, 112.5, 111.8, 108.0, 81.3,
77.8, 72.1, 57.4, 57.1, 57.0, 55.9, 46.5, 31.1, 29.7, 27.1, 25.2, 22.7. FTIR
(ReactIR): 1756, 1732, 1700, 1652, 1560. HRMS (ESI): calculated [M
+ H]+ 657.2330, found 657.2318. [α]D25: −47.9, (c = 0.85, CHCl3).
Compound 108: 1H NMR: (400 MHz, CDCl3): δ 13.23 (s, 1H), 7.84
(s, 1H), 7.34 (d, J = 9.1 Hz, 1H), 7.24 (s, 1H), 6.72 (s, 1H), 5.69 (dt, J =
9.3, 4.2 Hz, 1H), 5.35 (s, 1H), 5.12 (d, J = 10.0 Hz, 1H), 4.39−4.24 (m,
1H), 4.15 (d, J = 1.3 Hz, 1H), 3.99 (s, 3H), 3.96 (d, J = 1.5 Hz, 6H),
3.58 (d, J = 13.8 Hz, 1H), 3.17 (d, J = 13.9 Hz, 1H), 2.47 (s, 3H), 2.10
(d, J = 18.5 Hz, 1H), 1.45 (s, 3H), 1.35 (s, 3H). 13C NMR (101 MHz,
CDCl3): FTIR (ReactIR): 1767, 1737, 1701, 1631, 1521. HRMS
(ESI): calculated [M + H]+ 657.2330, found 657.2326. [α]2D5: −29.3, (c
= 0.075, CHCl3).
Compound 102. Prepared as previously reported with 2,5-
methoxybenzoic acid 101 (9.1 g, 50 mmol) and thionyl chloride (8
mL, 110 mmol, 2.2 equiv) and then CH2Cl2 (38 mL, 1.3 M) and Et2NH
(10.34 mL, 100 mmol, 2 equiv) to give compound 102 (3.87 g, 33%).62
Compound 103. Prepared as previously reported with THF (14.8
mL, 0.27 M), sec-butyl lithium (1.4 M in cyclohexane, 3.71 mL, 5.2
mmol, 1.3 equiv), tetramethylenediamine (774 μL, 5.2 mmol, 1.3
equiv), amide 102 (949 mg, 4 mmol) in THF (3 mL, 1.3 M), and DMF
(373 μL, 4.8 mmol, 1.2 equiv) to give the formylated amide 103 (782
mg, 74%).63
Compound 104. Prepared as previously reported with formylated
amide 103 (767 mg, 2.90 mmol), 1 N HCl (13.4 mL), and glacial acetic
acid (6.7 mL) to give the title lactol 104 (342 mg, 65%).64
Compound 105. Prepared as previously reported, lactol 104 (180
mg, 1 mmol), p-toluenesulfonic acid hydrate (9.5 mg, 0.05 mmol, 5 mol
%), MgSO4 (2 g, 1 g per mmol SM), and toluene (5 mL, 0.2 M) were
added to a flask and reflux condenser. Thiophenol (84 μL, 0.9 mmol,
0.9 equiv) was added, and the mixture was brought to boil for 3 h. The
mixture was cooled and quenched by the slow addition of aqueous
saturated NaHCO3. The mixture was extracted with EtOAc (100 mL).
The organic layers were washed with aqueous saturated NaHCO3,
water, and brine, followed by drying over Na2SO4, filtration, and
concentration on the rotary evaporator. The orange solid 105 was used
directly in the next step (252 mg, 83%).65 1H NMR (400 MHz,
General Procedure for Optimization of Triflation (Com-
pound 109, Table 3). A dry vial was charged with a base and a solvent.
Anthraquinone 18 (0.1 mmol to 0.01 mmol) was added in solvent
dropwise. Purple color denoted deprotonation of the red anthraqui-
none to its corresponding phenol. The triflating reagent (3 equiv) was
added afterward. Reactions were monitored by 1H NMR, as the starting
material and triflate 109 cospot as a yellow mixture on TLC (EtOAc).
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