S. Ra´dl et al. / Tetrahedron Letters 43 (2002) 2087–2090
2089
using Jones’ reagent. Pyridinium chromate, as well as
sodium chlorite, with or without a chlorine scavenger,
was also used for the oxidation without apparent
advantage. The last step, leading to the cis-racemate 2
was carried out according to the patented procedure
with tert-BuOH, DCC, and DMAP.
4. For examples see: (a) Barlett, P. A.; Myerson. J. Am.
Chem. Soc. 1978, 100, 3950–3952; (b) Bennett, F.;
Knight, D. W.; Fenton, G. J. Chem. Soc., Perkin Trans.
1 1991, 519–523.
5. For examples see: (a) Cardillo, G.; Orena, M.; Porzi, G.;
Sandri, S. J. Chem. Soc., Chem. Commun. 1981, 465–466;
(b) Barlett, P. A.; Meadows, J. D.; Brown, E. G.; Mori-
moto, A.; Jernstedt, K. K. J. Org. Chem. 1982, 47,
4013–4018; (c) Cardillo, G.; Orena, M.; Porzi, G.; Sandri,
S.; Tomasini, C. J. Org. Chem. 1984, 49, 701–703; (d)
Duan, J. J.-W.; Smith, A. B., III. J. Org. Chem. 1993, 58,
3703–3711; (e) Ley, S. V.; Norman, J.; Pinel, C. Tetra-
hedron Lett. 1994, 35, 2095–2098.
Since we hoped, that this modification can also be used
for production of larger amounts of the (4R,6R)-isomer
of 2, which serves as a key intermediate for atorvastatin
synthesis, we tried to circumvent the potentially haz-
ardous ozonization step. Compound 7 was smoothly
oxidized with mCPBA to give satisfactory yields of
epoxy derivative 11. This compound could be
hydrolyzed to the corresponding vicinal dihydroxy
derivative, which should be easily oxidized to the corre-
sponding aldehyde 8 with sodium periodate without the
necessity to use highly toxic osmium(VIII) oxide.8 We
found that epoxy derivative 11 can be directly oxidized
with periodic acid at room temperature by a slight
modification of the published procedure9 to yield alde-
hyde 8. An attempt to prepare 9 by a direct oxidation
of epoxy derivative 11 using chromium(VI) oxide and
periodic acid in aqueous acetone at ambient
temperature10 failed.
6. Duan, J. J.-W.; Sprengeler, P. A.; Smith, A. B., III.
Tetrahedron Lett. 1992, 35, 6439–6442.
7. Butler, D. E.; Deering, C. F.; Millar, A.; Nanninga, T.
N.; Roth, B. D. (Warner-Lambert Co.) US Patent
5,245,047.
8. Minami, T.; Takahashi, K.; Hiyama, T. Tetrahedron Lett.
1993, 34, 513.
9. Sih, C. J.; Salomon, R. G.; Price, P.; Sood, R.; Peruz-
zotti, G. J. Am. Chem. Soc. 1975, 97, 857–865.
10. (a) Schithenner, H. F.; Weinreb, S. M. J. Org. Chem.
1980, 45, 3372–3373; (b) Khatri, N. A.; Schithenner, H.
F.; Shingarpure, J.; Weinreb, S. M. J. Am. Chem. Soc.
1981, 103, 6387–6393.
In our attempts to obtain pure optical isomers of 2, we
prepared various salts of 9 with optically active amines,
e.g. (R)-(+)-1-phenylethylamine, (S)-(−)-1-phenylethyl-
amine, quinine and quinidine, and crystallized them
from various solvents. The chiral purity of the recov-
ered acid 9 was determined by HPLC on a cellulose
tris(3,5-dimethylphenyl carbamate) chiral column, after
the conversion to 2 as previously described.11 However,
none of these conditions led to a useful level of
resolution.
11. Mann, E. E.; Palmer, C. W.; Hagen, S. R. J. Liq. Chrom.
Relat. Technol. 1997, 20, 2441–2450.
12. 1H NMR (CDCl3); compound 2: l 4.28 dddd (J=2.5,
4.5, 7.6, 8.2 Hz), 1H [-CH(-O-)-]; 4.14 ddt, (J=1.6, 7.6
Hz), 1H [-CH(-O-)-]; 2.51 dd, (J=1.6, 7.6 Hz), 2H
(CH2CN); 2.47 dd (J=8.2, 14.2 Hz), 1H (CH2CꢀO); 2.33
dd (J=2.5, 14.2 Hz), 1H (CH2CꢀO); 1.75 dt (J=4.5, 7.6
Hz), 1H (CH2); 1.46 s, 9H, (CH3); 1.45 q (J=0.6 Hz), 3H
(CH3); 1.38 q (J=0.6 Hz), 3H (CH3); 1.32 dt, 1H (CH2).
Compound 4: l 5.80 ddt (J=7.0, 9.8, 17.3 Hz), 1H
(-CHꢀ); 5.21 m, 2H (CH2ꢀ); 4.54 ddt (J=3.1, 6.23, 12.0
Hz), 1H [-CH(-O-)-]; 4.46 dddd (J=3.1, 4.5, 6.9, 11.5
Hz), 1H [-CH(-O-)-]; 3.40 dd (J=4.5, 10.7 Hz), 1H
(CH2I); 3.30 dd (J=6.9, 10.7 Hz), 1H (CH2I); 2.61–2.38
m, 2H (-CH2-Cꢀ); 2.38 dt (J=3.1, 14.2 Hz), 1H (CH2);
1.72 dt (J=12.0, 14.2 Hz), 1H (CH2). Compound 7: l
5.79 dddd (J=6.5, 7.4, 10.3, 17.1 Hz), 1H (-CHꢀ); 5. 10
dddt (J=1.3, 1.6, 2.2, 17.1 Hz), 1H (CH2ꢀ); 5.08 dddt
(J=1.0, 1.3, 2.2, 10.3 Hz), 1H (CH2ꢀ); 4.11 ddt, (J=2.5,
6.0, 6.2 Hz), 1H [-CH(-O-)-]; 3.91 ddt, (J=2.5, 6.0, 6.6
Hz), 1H [-CH(-O-)-]; 2.54 dd (J=6.0, 16.6 Hz), 1H
(CH2CN); 2.46 dd (J=6.2, 16.6 Hz), 1H (CH2CN); 2.33
ddddt (J=1.3, 1.6, 6.0, 6.5, 14.1 Hz), 1H (-CH2-Cꢀ); 2.17
ddddt (J=1.0, 1.3, 6.6, 7.4, 14.1 Hz), 1H (-CH2-Cꢀ); 1.68
dt (J=2.5, 12.8 Hz), 1H (CH2); 1.26 dt (J=11.5, 12.8
Hz), 1H (CH2); 1.45 q (J=0.7 Hz), 3H (CH3); 1.40 q
(J=0.7 Hz), 3H (CH3). Compound 8: l 9.77 dd (J=1.5,
1.8 Hz), 1H (CHꢀO); 4.47 dddt (J=2.5, 5.9, 7.1, 11.7
Hz), 1H [-CH(-O-)-]; 4.18 dddt, (J=2.5, 5.9, 8.5, 11.7
Hz), 1H [-CH(-O-)-]; 2.65 dd, (J=7.1, 12.6 Hz), 1H
(CH2CN); 2.52 dd (J=5.9, 12.8 Hz), 1H (CH2CN); 2.48
m, 2H (CH2CꢀO); 1.76 dt (J=2.5, 12.6 Hz), 1H (CH2);
1.48 q (J=0.5 Hz), 3H (CH3); 1.39 q (J=0.5 Hz), 3H
(CH3); 1.16 dt (J=11.7, 12.6), 1H (CH2). Compound 9: l
4.33 dddd (J=2.6, 4.5, 7.1, 8.2 Hz), 1H [-CH(-O-)-]; 4.20
ddt, (J=4.5, 6.0, 8.4 Hz), 1H [-CH(-O-)-]; 2.50 m, 2H
(CH2CN); 2.47 dd (J=8.2, 16.4 Hz), 1H (CH2CꢀO); 2.33
1
The prepared compounds were characterized by H,12
13C NMR,13 IR14 and GC–MS.15
Acknowledgements
Financial support provided by Leciva Praha is greatly
appreciated.
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