Job/Unit: O20627
/KAP1
Date: 25-07-12 17:02:28
Pages: 10
Synthesis of Coenzyme Q10
(s, 3 H), 1.59 (s, 24 H), 1.67 (s, 3 H), 1.76 (s, 3 H), 1.93–2.02 (m,
4-(Benzenesulfonyl)-3,7,11,15,19,23,27,31,35,39-decamethyl-1-(3-iso-
18 H), 2.02–2.10 (m, 18 H), 2.13 (s, 3 H), 3.31 (d, J = 6.4 Hz, 2 propoxy-2-methyl-4,5,6-trimethoxyphenyl)tetraconta-2,6,10,14,18,
H), 3.77 (s, 3 H), 3.88 (s, 6 H), 3.95 (q, J = 7.2 Hz, 2 H), 5.03 (t,
J = 6.4 Hz, 1 H), 5.11 (t, J = 6.4 Hz, 9 H) ppm. 13C NMR: δ =
11.9, 15.8, 16.0, 16.0, 16.1, 16.2, 17.7, 25.7, 25.8, 26.6, 26.7, 26.8,
39.7, 39.7, 61.0, 61.0, 61.1, 122.9, 124.1, 124.2, 124.2, 124.4, 125.6,
129.1, 131.2, 134.8, 134.9, 134.9, 135.0, 135.0, 144.6, 145.0, 147.0,
147.5 ppm. HRMS (FAB+): calcd. for C62H98O4 906.7465; found
906.7461.
22,26,30,34,38-decaene (5c): Following the same procedure as for
5b, the reaction of the carbanion generated from 4c (0.46 g,
1.02 mmol) and tBuOK (0.15 g, 1.30 mmol) with solanesyl bromide
(0.85 g, 1.23 mmol) in THF (10 mL) at –20 °C for 1.5 h produced
5c (0.42 g, 0.40 mmol, 39%) as a clear liquid after purification by
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SiO2 column chromatography. Data for 5c: H NMR: δ = 1.25 (d,
J = 6.0 Hz, 3 H), 1.26 (d, J = 6.0 Hz, 3 H), 1.57 (s, 6 H), 1.60 (s,
21 H), 1.68 (s, 3 H), 1.83 (s, 3 H), 1.92 (s, 3 H), 1.94–2.02 (m, 16
H), 2.02–2.11 (m, 16 H), 2.54–2.66 (m, 1 H), 2.76–2.86 (m, 1 H),
3.14 (d of A of ABq, JAB = 15.2, Jd = 6.4 Hz, 1 H), 3.25 (d of B
of ABq, JAB = 15.2, Jd = 7.2 Hz, 1 H), 3.47 (dd, J = 11.6, 3.6 Hz,
1 H), 3.65 (s, 3 H), 3.86 (s, 3 H), 3.86 (s, 3 H), 4.33 (septet, J =
6.4 Hz, 1 H), 4.87 (t, J = 6.0 Hz, 1 H), 4.92 (t, J = 6.0 Hz, 1 H),
5.05 (t, J = 6.0 Hz, 1 H), 5.11 (t, J = 6.4 Hz, 7 H), 7.40–7.46 (m,
2 H), 7.50–7.56 (m, 1 H), 7.74–7.80 (m, 2 H) ppm. 13C NMR: δ =
12.6, 12.7, 14.0, 16.0, 16.3, 16.3, 17.7, 22.6, 22.7, 24.0, 25.3, 25.7,
26.1, 26.5, 26.7, 26.7, 26.7, 39.7, 39.7, 60.7, 61.0, 61.0, 73.8, 75.4,
118.6, 123.7, 124.1, 124.2, 124.2, 124.4, 125.9, 126.6, 127.2, 128.6,
128.8, 128.9, 129.1, 131.0, 132.9, 133.3, 133.3, 133.6, 134.9, 134.9,
134.9, 134.9, 135.0, 135.3, 137.9, 138.5, 144.6, 145.8, 146.1,
Coenzyme Q10 (1) from 5bЈ: A solution of ammonium cerium(IV)
nitrate (0.79 g, 1.44 mmol) in H2O (3 mL) and 64% HNO3
(0.06 mL, 0.96 mmol) were added to a stirred solution of 5bЈ
(0.44 g, 0.48 mmol) in MeCN (8 mL) and THF (8 mL) at 0 °C. The
mixture was stirred at 0 °C for 30 min, and the organic layer was
separated. The aqueous layer was extracted with CH2Cl2. The com-
bined organic extracts were washed with HCl (1 m), dried with an-
hydrous Na2SO4, filtered, and concentrated under reduced pres-
sure. The crude product was purified by SiO2 column chromatog-
raphy to give 1 (0.61 g, 0.35 mmol, 72%) as an orange solid. Data
for 1: 1H NMR: δ = 1.55 (s, 3 H), 1.58 (s, 3 H), 1.60 (s, 18 H), 1.68
(s, 6 H), 1.74 (s, 3 H), 1.93–2.02 (m, 18 H), 2.01 (s, 3 H), 2.02–2.13
(m, 18 H), 3.18 (d, J = 7.2 Hz, 2 H), 3.98 (s, 3 H), 3.99 (s, 3 H),
4.94 (t, J = 7.2 Hz, 1 H), 5.06 (t, J = 6.8 Hz, 1 H), 5.11 (t, J =
6.8 Hz, 8 H) ppm. 13C NMR: δ = 14.4, 18.5, 18.5, 18.8, 20.2, 25.9,
27.8, 28.2, 29.0, 29.0, 29.1, 29.1, 29.2, 29.2, 29.3, 34.5, 42.2, 42.2,
42.5, 63.5, 63.5, 121.5, 126.3, 126.6, 126.8, 126.9, 127.5, 133.7,
137.3, 137.4, 137.4, 137.5, 140.1, 141.3, 144.2, 146.7, 146.9, 186.4,
187.2 ppm.
147.5 ppm. IR (KBr): ν = 1446, 1415, 1382, 1355, 1304, 1197, 1146,
˜
1105, 1083, 1066, 1039, 985, 925 cm–1. HRMS (FAB+): calcd. for
C69H104O6S 1060.7554; found 1060.7565.
3,7,11,15,19,23,27,31,35,39-Decamethyl-1-(3-isopropoxy-2-methyl-
4,5,6-trimethoxyphenyl)tetraconta-2,6,10,14,18,22,26,30,34,38-de-
caene (5cЈ): Following the same procedure as for 5bЈ, The reaction
of 5c (0.85 g, 0.80 mmol), Pd(dppe)Cl2 (23 mg, 0.04 mmol), and a
THF solution (1 m) of LiEt3BH (1.60 mL, 1.60 mmol) in THF
(10 mL) at room temp. for 2 h produced 5cЈ (0.63 g, 0.68 mmol,
2-Isopropoxy-3,4,5-trimethoxy-1-methylbenzene (2c): 2,3,4-Trimeth-
oxy-6-methylphenol (6) (3.0 g, 15.1 mmol) was added to a stirred
suspension of NaH (0.72 g, 30.26 mmol) in DMF (30 mL) at 0 °C.
The resulting black solution was stirred at that temperature for
30 min, and then 2-bromopropane (2.84 mL, 30.26 mmol) was
added. The mixture was stirred at 0 °C for 11 h, then warmed up
to room temperature, and H2O was added to the mixture. The mix-
ture was extracted with CH2Cl2, washed with NaOH (1 m), dried
with anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. The crude product was purified by SiO2 column
chromatography to give 2c (2.37 g, 9.86 mmol, 65%) as a clear li-
quid. Data for 2c: 1H NMR: δ = 1.25 (d, J = 6.0 Hz, 6 H), 2.18 (s,
3 H), 3.79 (s, 3 H), 3.83 (s, 3 H), 3.86 (s, 3 H), 4.34 (septet, J =
6.0 Hz, 1 H), 6.42 (s, 1 H) ppm. 13C NMR: δ = 16.5, 25.4, 55.8,
60.5, 60.9, 74.9, 108.1, 126.4, 140.6, 143.0, 147.0, 148.5 ppm. IR
86%) as
a clear liquid after purification by SiO2 column
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chromatography. Data for 5cЈ: H NMR: δ = 1.27 (d, J = 6.4 Hz,
6 H), 1.58 (s, 3 H), 1.60 (s, 24 H), 1.68 (s, 3 H), 1.76 (s, 3 H), 1.94–
2.02 (m, 18 H), 2.02–2.11 (m, 18 H), 2.12 (s, 3 H), 3.31 (d, J =
6.4 Hz, 2 H), 3.78 (s, 3 H), 3.86 (s, 3 H), 3.89 (s, 3 H), 4.36 (septet,
J = 6.4 Hz, 1 H), 5.03 (t, J = 6.4 Hz, 1 H), 5.11 (t, J = 6.8 Hz, 9
H) ppm. 13C NMR: δ = 12.6, 16.0, 16.2, 17.7, 22.7, 25.7, 25.9, 26.7,
26.7, 26.8, 39.7, 60.8, 61.1, 61.1, 123.0, 124.1, 124.2, 124.3, 124.4,
126.1, 129.1, 131.2, 134.9, 134.9, 135.0, 144.7, 145.1, 145.8,
147.2 ppm. HRMS (FAB+): calcd. for C63H100O4 920.7622; found
920.7623.
Coenzyme Q10 (1) from 5cЈ: Following the same CAN oxidation
procedure as was used starting from 5bЈ, the reaction of 5cЈ (0.18 g,
0.19 mmol), a solution of ammonium cerium(IV) nitrate (0.31 g,
0.57 mmol) in H2O (1 mL), and 64% HNO3 (0.02 mL, 0.38 mmol)
in MeCN (3 mL) and THF (3 mL) at 0 °C for 30 min produced 1
(0.13 g, 0.15 mmol, 79%) as an orange solid after purification by
SiO2 column chromatography.
(KBr): ν = 1491, 1464, 1410, 1377, 1344, 1228, 1194, 1126, 1086,
˜
1039, 993, 930, 926 cm–1. HRMS (EI+): calcd. for C13H20O4
240.1362; found 240.1359.
1-(Benzenesulfonyl)-4-(3-isopropoxy-2-methyl-4,5,6-trimethoxy-
phenyl)-2-methylbut-2-ene (4c): Following the same procedure as for
4b, the reaction of 2c (0.35 g, 1.47 mmol), 3a (0.30 g, 1.23 mmol),
and FeCl3 (0.06 g, 0.37 mmol) in CH2Cl2 (10 mL) at 40 °C for 24 h
produced 4c (0.19 g, 0.42 mmol, 35%) as a clear liquid after purifi-
cation by SiO2 column chromatography. The crude product was a
1-(Benzenesulfonyl)-2-methyl-4-(2-methyl-3,4,5,6-tetramethoxy-
phenyl)but-2-ene (4a): Compound 3a (1.00 g, 4.09 mmol) and FeCl3
(0.21 g, 1.23 mmol) were added to a stirred solution of tetrameth-
oxytoluene (2a) (1.05 g, 4.90 mmol) in CH2Cl2 (30 mL). The mix-
ture was heated at 40 °C for 8 h, then allowed to cool to room
temperature, diluted with CH2Cl2, washed with 10% NH4Cl, dried
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27:1 mixture of E/Z isomers (by HPLC analysis). Data for 4c: H
NMR: δ = 1.27 (d, J = 6.4 Hz, 3 H), 1.94 (s, 3 H), 1.98 (s, 3 H),
3.24 (d, J = 6.4 Hz, 2 H), 3.70 (s, 3 H), 3.71 (s, 2 H), 3.87 (s, 6 H),
4.34 (septet, J = 6.4 Hz, 1 H), 4.92 (t, J = 6.4 Hz, 1 H), 5.59 (t, J
= 8.0 Hz, 1 H, Z-isomer), 7.40–7.46 (m, 2 H), 7.51–7.57 (m, 1 H), with anhydrous Na2SO4, filtered, and concentrated under reduced
7.76–7.81 (m, 2 H) ppm. 13C NMR: δ = 12.6, 14.3, 17.0, 22.6, 26.3,
55.8, 60.7, 60.9, 61.0, 66.0, 123.2, 125.4, 127.0, 128.4, 128.8, 133.3,
pressure. The crude product was a 8.5:1 mixture of E/Z isomers
(by HPLC analysis), which was purified by recrystallization from a
4:1 mixture of MeOH/EtOH to give 4a (1.16 g, 2.75 mmol, 67%) as
a white solid (E/Z = 37:1). Data for 4a: M.p. 78–80 °C. 1H NMR: δ
= 1.94 (s, 3 H), 1.98 (s, 3 H), 3.24 (d, J = 7.2 Hz, 2 H), 3.70 (s, 3
H), 3.71 (s, 2 H), 3.77 (s, 3 H), 3.87 (s, 3 H), 3.91 (s, 3 H), 4.92 (t,
134.5, 138.2, 144.6, 145.5, 145.7, 147.1 ppm. IR (KBr): ν = 1466,
˜
1448, 1415, 1354, 1309, 1252, 1151, 1134, 1103, 1084, 1039, 985,
924 cm–1. HRMS (CI+): calcd. for C24H33O6S 449.1998; found
449.2000.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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