P. Bovicelli et al. / Tetrahedron Letters 46 (2005) 1255–1257
1257
BF *Et O / Et O
H
3
2
2
H
Br
-
+
3
H CO
3
O
H CO
3
O Na
3
-20˚, conv. 90%, 75%
THF, 10˚, 95%
OCH
OCH
3
3
7
8
H
3
H
3
O
Na CO /Pyr/toluene
2
3
H CO
3
OH
H CO
3
O /CoSalen/CH CN
O
2
3
OCH
3
OCH
R.T., 70%
3
9
10
Scheme 3. Synthesis of CoQ3.
9. Blaha, L.; Weichet, J. Collect. Czechoslov. Chem. Commun.
1965, 30, 2068–2073.
10. Bovicelli, P.; Mincione, E.; Antonioletti, R.; Bernini, R.;
Colombari, M. Synth. Commun. 2001, 31, 67; Bovicelli, P.;
Bernini, R.; Antonioletti, R.; Mincione, E. Tetrahedron
Lett. 2002, 43, 5563.
By treating 8 with BF3 etherate at ꢀ20 °C an almost
complete conversion of it into two compounds occurred,
resulting from the shift of the alkenyl chain to the ortho
(75%) and para (25%) positions, with respect to the ini-
tial position of the ethereal moiety. From the crude,
product 9 could be easily separated by flash chromato-
graphy and submitted to the oxidation reaction
promoted by Co(salen).15
11. A Varian Mercury 300 MHz instrument was used to
record NMR spectra. All compounds were isolated as oils.
1
Significant data for key compounds. 3: NMR d (ppm):
7.50 (1H, d, J = 2.2 Hz, Ar–H), 7.33 (1H, d, J = 2.2 Hz,
Ar–H), 3.81 (3H, s, CH3O); 18C NMR d (ppm): 199.6
(C@O), 153.8 (ArC–OCH3), 129.3 (ArC–CO), 117.8
(ArC–Br), 62.2 (CH3O), 30.4 (CH3CO), 20.3 (CH3). 4:
1H NMR d (ppm): 7.23 (1H, d, J = 2.2 Hz, Ar–H), 6.82
(1H, d, J = 2.2 Hz, Ar–H), 2.32 (3H, s, CH3CO); 13C
NMR d (ppm): 168.8 (COO), 147.0 (ArC–O), 144.2 (ArC–
OCO), 117.2 (ArC–Br), 60.9 (CH3O), 20.6 (CH3COO). 6:
1H NMR d (ppm): 6.42 (1H, d, J = 1.5 Hz, Ar–H), 6.29
(1H, d, J = 1.5 Hz, Ar–H), 3.85 (3H, s, CH3O), 3.84 (3H,
s, CH3O), 2.26 (3H, s, ArCH3); 13C NMR d (ppm): 152.0
and 149.0 (ArC–OH and ArC–O), 134.0 and 133.4 (ArC–
The final step was much more efficient than previ-
ously observed in the case of iridol and gave high
yields of CoQ3 10, the ubiquinone with the farnesyl side
chain.
The exploitation of the same strategy in the synthesis of
higher order ubiquinones by using suitable polyisopre-
nols is presently our main purpose. Besides, iridol has
the correct functionalities for acting as a good scavenger
of free radicals, and a number of derivatives can be pre-
pared with this objective.
1
O and ArC–Me), 60.8 (CH3O), 55.7 (CH3O). 8: H NMR
d (ppm): 6.40 (2H, bs, 2Ar–H), 5.11 (1H, t, J = 6.6 Hz, C–
CH@C), 4.60 (2H, d, J = 6.6 Hz, O–CH2–C@C); 13C
NMR d (ppm): 65.5 (Ar–O–CH2), 60.2 (CH3O), 55.5
(CH3O). 9: 1H NMRd (ppm): 6.27 (Ar–H), 3.88 (3H,
s, CH3O), 3.83 (3H, s, CH3O), 3.30 (2H, d, J = 6.6 Hz, Ar–
CH2–C). 13C NMR d (ppm): 60.9 (CH3O), 55.7 (CH3O),
16.1 (Ar–CH2).
References and notes
1. Kaikkonen, J.; Nyyssonen, K.; Porkkala-Sarataho, E.;
Poulsen, S. H.; Metsa-Ketela, T.; Hayn, M.; Salonen, R.;
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(C) 1969, 308–312; Bacon, R. G. R.; Rennison, S. C. J.
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Kuilman, T.; Piekstra, O. G.; Hulshof, L. A.; Sheldon, R.
A. Tetrahedron 1989, 45, 5565–5578.
13. For mechanistic considerations of the copper catalysed
nucleophilic substitution reaction of sodium methoxide
with bromobenzene derivatives see: Aalten, H. L.; van
Koten, G.; Grove, D. M.; Kuilman, T.; Piekstra, O. G.;
Hulshof, L. A.; Sheldon, R. A. Tetrahedron 1989, 45,
5565–5578.
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14. Other bromo aryls such as 2,6-dibromo-4-methyl-phenol,
2-bromo-4-(2-hydroxy-ethyl)-phenol, 2,6-dibromo-4-(2-
5. Lu, L.; Chen, F. Synth. Commun. 2004, 34(22), 4049–
4053.
6. Masaki, Y.; Hashimoto, K.; Kaji, K. Chem. Pharm. Bull.
1994, 32, 3952–3958; Keinan, E.; Eren, D. J. Org. Chem.
1987, 52, 3872–3875.
hydroxy-ethyl)-phenol,
biphenyl gave the corresponding methoxy derivatives in
good to excellent yields.
5,50-dibromo-2,20-dimethoxy-
15. Benzendale, I. R.; Lee, A.-L.; Ley, S. V. Synlett 2001, 9,
1482.
7. Merz, A.; Rauschel, M. Synthesis 1993, 797–802.
8. Lipshutz, B. H. US 6,545,184 B1 (2003-04-08).