UPDATES
Shihui Liu et al.
Compound 3d: White solid; yield 92%; mp 43–468C;
1H NMR (300 MHz, CDCl3) d 7.42 (d, J=8.6 Hz, 2H), 7.30
(d, J=8.7 Hz, 2H), 3.10 (s, 1H); 13C NMR (75 MHz, CDCl3)
d 134.9, 133.3, 128.7, 120.6, 82.6, 78.2.
Compound 3q: Colorless oil; yield 67%; 1H NMR
(400 MHz, CDCl3) d 7.27 (dd, J=8.9, 5.8 Hz, 2H), 7.23–7.14
(m, 3H), 2.82 (t, J=7.6 Hz, 2H), 2.45 (td, J=7.6, 2.6 Hz,
2H), 1.95 (t, J=2.6 Hz, 1H); 13C NMR (101 MHz, CDCl3) d
140.5, 129.3, 128.5, 126.5, 83.9, 69.1, 34.9, 20.7.
Compound 3e: Colorless oil; yield 92%; 1H NMR
(300 MHz, CDCl3) d 7.53 (dd, J=7.5, 1.8 Hz, 1H), 7.41 (dd,
J=7.8, 1.5 Hz, 1H), 7.42–7.19 (m, 2H), 3.37 (s, 1H);
13C NMR (75 MHz, CDCl3) d 136.2, 134.0, 129.9, 129.3,
126.4, 122.0, 82.4, 80.2.
Total synthesis of dihydroxerulin
Synthesis of alcohol 9 by Julia-Kocienski reaction: A solu-
tion of compound 8 (1.03 g, 2.6 mmol) in dry THF (12 mL)
was cooled to À788C under argon. LiHMDS (1.0M in
hexane, 2.6 mL) was added through a syringe within 15 min.
The reaction was stirred at À788C for 15 min before a solu-
tion of aldehyde 7 (292 mg, 2.0 mmol) in THF (4 mL) was
added within 15 min. The reaction temperature was allowed
to rise to 08C within 2 h. Water (15 mL) was added to
quench the reaction and THF was removed under reduced
pressure. The residue was extracted with EtOAc (3ꢂ
15 mL). The combined organic layer was washed with brine
(15 mL), dried over Na2SO4 and concentrated under re-
duced pressure. The crude product was dissolved in MeOH
(12 mL), hydrochloric acid (12M, 0.6 mL) was added slowly,
and the reaction mixture was stirred at rt for 10 min. Brine
(30 mL) was added, and the mixture was extracted with
EtOAc (3ꢂ15 mL). The combined organic layer was washed
sequentially with water (10 mL), aqueous NaHCO3 (10 mL)
and brine (10 mL), dried over Na2SO4 and concentrated
under reduced pressure. The crude product was purified by
column chromatography to give 218 mg desired product
(E)-9 (yield 54% for two steps) and 102 mg by-product (Z)-
Compound 3 f: White solid; yield 92%; mp 156–1588C;
1H NMR (400 MHz, CDCl3) d 7.62 (d, J=8.4 Hz, 2H), 7.56
(d, J=8.4 Hz, 2H), 3.32 (s, 1H); 13C NMR (101 MHz,
CDCl3) d 133.1, 132.5, 127.4, 118.7, 112.8, 82.3, 82.1.
Compound 3g: White solid; yield 93%; mp 147–1498C;
1H NMR (400 MHz, CDCl3) d 8.20 (d, J=8.8 Hz, 2H), 7.64
(d, J=8.8 Hz, 2H), 3.36 (s, 1H); 13C NMR (101 MHz,
CDCl3) d 147.5, 132.9, 128.9, 123.5, 82.3, 81.6.
Compound 3h: Colorless oil; yield 94%; 1H NMR
(400 MHz, CDCl3) d 8.30 (s, 1H), 8.19 (dd, J=8.3, 0.9 Hz,
1H), 7.78 (d, J=7.7 Hz, 1H), 7.52 (t, J=8.0 Hz, 1H), 3.24
(s, 1H); 13C NMR (101 MHz, CDCl3) d 148.0, 137.8, 129.4,
126.9, 123.9, 123.5, 81.1, 79.9.
Compound 3i: Colorless oil; yield 86%; 1H NMR
(300 MHz, CDCl3) d 7.43 (d, J=8.8 Hz, 2H), 6.84 (d, J=
8.8 Hz, 2H), 3.80 (s, 3H), 3.00 (s, 1H); 13C NMR (75 MHz,
CDCl3) d 159.9, 133.6, 114.1, 113.9, 83.9, 83.7, 55.3.
Compound 3j: Colorless oil; yield 83%; 1H NMR
(300 MHz, CDCl3) d 7.46 (dd, J=7.5, 1.7 Hz, 1H), 7.32 (dt,
J=8.1, 1.7 Hz, 1H), 6.96–6.85 (m, 2H), 3.90 (s, 3H), 3.31 (s,
1H); 13C NMR (75 MHz, CDCl3) d 160.5, 134.2, 130.3,
120.4, 111.1, 110.6, 81.1, 80.1, 55.8.
1
9 (yield 25% for two steps). (E)-9: Colorless oil; H NMR
Compound 3k: Colorless oil; yield 87%; 1H NMR
(300 MHz, CDCl3) d 7.23 (t, J=9.0 Hz, 1H), 7.09 (d, J=
7.6 Hz, 1H), 7.02 (s, 1H), 6.91 (dd, J=8.3, 2.6 Hz, 1H), 3.80
(s, 3H), 3.06 (s, 1H); 13C NMR (75 MHz, CDCl3) d 159.2,
129.4, 124.6, 123.0, 116.9, 115.4, 83.5, 77.2, 55.3.
(300 MHz, CDCl3) d 6.62 (dd, J=15.6, 10.8 Hz, 1H), 6.10
(m, 1H), 5.82 (m, 1H), 5.48 (d, J=15.6 Hz, 1H), 3.60 (t, J=
6.6 Hz, 2H), 2.28 (m, 2H), 2.18 (m, 2H), 1.98 (br, 1H), 1.64
(m, 2H), 1.56 (m, 2H), 0.98 (t, J=7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3) d 144.5, 138.2, 130.0, 108.1, 85.2, 76.3,
74.6, 65.5, 62.1, 31.8, 29.1, 21.8, 21.6, 13.5; HR-MS (ESI)
m/z calcd. for C14H19O [M + H]+ 203.1436, found 203.1431.
Synthesis of aldehyde 11: To a solution of alcohol 9
(202 mg, 1.0 mmol) in DMSO (2.0 mL) and CH3CN
(3.0 mL) was added 2-iodoxybenzoic acid (IBX, 700 mg,
2.5 mmol) and catalyst 10 (51 mg, 0.20 mmol). The resulting
mixture was stirred at rt until the reaction was completed
(monitored by TLC). Direct column chromatography on
silica gel gave 129 mg (65%) of desired polyene aldehyde 11
(E:Z> 10:1). 1H NMR (300 MHz, CDCl3) d 9.57 (d, J=
7.8 Hz, 1H), 7.09 (dd, J=15.3, 10.8 Hz, 1H), 6.70 (m, 2H),
6.51 (dd, J=13.8, 11.1 Hz, 1H), 6.19 (dd, J=15.3, 7.8 Hz,
1H), 5.85 (d, J=14.4 Hz, 1H), 2.32 (t, J=6.9 Hz, 2H), 1.63–
1.51 (m, 2H), 0.99 (t, J=7.4 Hz, 3H); 13C NMR (75 MHz,
CDCl3) d 193.1, 150.3, 142.4, 140.4, 132.7, 132.3, 115.9, 88.2,
81.1, 74.0, 65.3, 21.7, 13.4; HR-MS (ESI) m/z calcd. for
C14H15O [M + H]+ 199.1123, found 199.1132.
Compound 3l: Colorless oil; yield 87%; 1H NMR
(300 MHz, CDCl3) d 8.36 (d, J=8.2 Hz, 1H), 7.83 (d, J=
8.1 Hz, 2H), 7.73 (d, J=7.1 Hz, 1H), 7.59–7.48 (m, 2H),
7.40 (t, J=7.7 Hz, 1H), 3.46 (s, 1H); 13C NMR (75 MHz,
CDCl3) d 133.5, 133.1, 131.3, 129.3, 128.3, 127.0, 126.5, 126.1,
125.1, 119.8, 82.1, 81.8.
Compound 3m: Yellow solid; yield 72%; mp 67–698C;
1H NMR (600 MHz, CDCl3) d 7.80 (d, J=4.2 Hz, 1H), 7.17
(d, J=4.2 Hz, 1H), 3.58 (s, 1H); 13C NMR (151 MHz,
CDCl3) d 132.2, 129.2, 128.1, 86.0, 75.1.
Compound 3n: Yellow solid; yield 77%; mp 52–548C;
1H NMR (400 MHz, CDCl3) d 7.30 (d, J=3.6 Hz, 1H), 6.80
(d, J=3.7 Hz, 1H), 3.56 (s, 1H); 13C NMR (151 MHz,
CDCl3) d 138.0, 118.3, 111.9, 85.5, 71.7.
Compound 3o: White solid; yield 68%; mp 162–1648C;
1H NMR (400 MHz, CDCl3) d 7.97 (d, J=8.3 Hz, 1H), 7.79
(s, 1H), 7.76 (d, J=8.4 Hz, 2H), 7.63 (d, J=7.8 Hz, 1H),
7.35 (t, J=7.9 Hz, 1H), 7.26 (dd, J=15.1, 7.5 Hz, 1H), 7.18
(d, J=8.2 Hz, 2H), 3.26 (s, 1H), 2.28 (s, 3H); 13C NMR
(101 MHz, CDCl3) d 145.5, 134.8, 134.1, 130.8, 130.1, 130.0,
127.0, 125.6, 123.9, 120.5, 113.6, 104.1, 81.7, 75.0, 21.6.
Compound 3p: Colorless oil; yield 93%; 1H NMR
(300 MHz, CDCl3) d 7.46–7.30 (m, 2H), 7.25 (m, 1H), 6.98–
6.80 (m, 2H), 6.20 (dd, J=16.5, 2.3 Hz, 1H), 3.82 (s, 3H),
3.03 (d, J=2.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 157.0,
138.6, 130.0, 127.0, 124.8, 120.7, 111.0, 107.5, 83.8, 78.7, 54.5.
Synthesis of dibromoalkene 12: To a solution of Ph3P
(472 mg, 1.80 mmol) in CH2Cl2 (2 mL) at 08C was added
CBr4 (306 mg, 0.92 mmol). The mixture was stirred at 08C
for 30 min before
a solution of aldehyde 11 (80 mg,
0.4 mmol) in CH2Cl2 (1.0 mL) was added. The reaction was
stirred at 08C for 30 min. Et2O (20 mL) was added and fil-
tered through Celite. The filtrate was concentrated under re-
duced pressure. The crude product was purified by column
chromatography to give 124 mg (88%) of desired product
6
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
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