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F. Legrand et al.
LETTER
H
H
References and Notes
H
CO2Me
CO2Me
i
(1) See, inter alia: (a) Cherfils, J.; Chardin, P. Trends Biochem.
Sci. 1999, 24, 306. (b) Takai, Y.; Sasaki, T.; Matozaki, T.
Physiol. Rev. 2001, 81, 153. (c) Marinissen, M. J.; Gutkind,
J. S. Trends Biochem. Sci. 2005, 30, 423. (d) Zeghouf, M.;
Guibert, B.; Zeeh, J.-C.; Cherfils, J. Biochem. Soc. Trans.
2005, 33, 1265. (e) Hall, A. Biochem. Soc. Trans. 2005, 33,
891.
MOMO
MOMO
I
CHO
H
4
21
iii
(2) Singleton, V. L.; Bohonos, N.; Ullstrup, A. J. Nature
(London) 1958, 181, 1072.
H
H
CO2Me
MeO2C
(3) See, for example: (a) Robineau, S.; Chabre, M.; Antonny, B.
Proc. Natl. Acad. Sci. U. S. A. 2000, 97, 9913. (b) Renault,
L.; Guibert, B.; Cherfils, J. Nature (London) 2003, 426, 525.
(c) Mossessova, E.; Corpina, R. A.; Goldberg, J. Mol. Cell.
2003, 12, 1403. (d) Cherfils, J.; Pacaud, P. Med. Sci. (Paris)
2004, 20, 393. (e) Pommier, Y.; Cherfils, J. Trends
Pharmacol. Sci. 2005, 26, 138.
(4) Archambaud, S.; Aphecetche-Julienne, K.; Guingant, A.
Synlett 2005, 139.
(5) Zeeh, J.-C.; Zeghouf, M.; Grauffel, C.; Guibert, B.; Martin,
E.; Dejaegere, A.; Cherfils, J. J. Biol. Chem. 2006, 281,
11805.
H
H
CO2Me
H
HO
ii
I
I
I
H
O
O
24
25
Scheme 7 Reagents and conditions: (i) anhyd CrCl2 (5.8 equiv),
CHI3 (2 equiv), 1,4-dioxane–THF (6:1), 20 °C, 72 h, 88%, see ref. 19
for more experimental details; (ii) PhSH (5 equiv), BF3·OEt2 (5
equiv), THF, 20 °C, 1 h, 92%; (iii) (MeO)2CH2 (70 equiv), P2O5 (20
equiv), CHCl3, 20 °C, 1 h, 93%.
(6) Gais, H. J.; Bülow, G.; Zatorski, A.; Jentsch, M.; Maidonis,
P.; Hemmerle, H. J. Org. Chem. 1989, 54, 5115.
(7) Yoshihisa, M.; Yoshiyasu, T.; Kazu, A. Chem. Pharm. Bull.
1987, 35, 2266.
(8) Ballini, R.; Bosica, G.; Fiorini, D.; Righi, P. Synthesis 2002,
681.
(9) Heating 9 in Ac2O (or in Ac2O with a catalytic amount of
DMAP) at reflux failed to give anhydride 6. Failure was also
encountered while attempting distillation of 9 in the
presence of a catalytic amount of sulfuric acid. However, 6
could be obtained in low yields when 9 was treated with
ClCO2Me and NMM (1.1 equiv each) in THF at 20 °C for 30
min (35%) or with TFA (4 equiv) in dioxane at 75 °C for 2 h
(38%).
(10) (a) Bolm, C.; Gerlach, A.; Dinter, C. L. Synlett 1999, 195.
(b) Bolm, C.; Schiffers, I.; Dinter, C. L.; Gerlach, A. J. Org.
Chem. 2000, 65, 6984.
Figure 1 X-ray crystal structure of 25
(11) (a) Deng, L.; Chen, Y.; Tian, S.-K. WO 2001074741, 2001.
(b) See also: Chen, Y.; Tian, S.-K.; Deng, L. J. Am. Chem.
Soc. 2000, 122, 9542.
(12) Enantiomeric ratio was determined by GPC using a Lipodex
E column; tR (the injector and detector temperatures were
220 °C): 74.9 min (major enantiomer) and 76.6 min (minor
enantiomer).
a pad of Celite and neutral alumina followed by purifica-
tion through a silica gel column [elution first with hexane
to remove iodoform in excess then with a EtOAc–PE mix-
ture (1:9)] afforded 4 (E/Z = 97:3) in up to 88% and in a
reproducible manner.
In conclusion, a synthesis of the methyl (1R,2R,4S)-2-
[(E)-2-iodovinyl]-4-(methoxymethoxy)-cyclopentanecar-
boxylate (4) has been achieved in nine steps from the
prochiral anhydride 6. By comparison with our previous
synthesis of brefeldin C, unanticipated difficulties due to
the presence and (or) the sensitive nature of the OMOM
group were encountered. However, we found conditions
to circumvent all of these difficulties and to reach 4 in
good overall yield (20% from 6). Use of vinylic iodide 4
as a scaffold to prepare several brefeldin A analogues is
under way and the results of these studies will be reported
in due course.
(13) This reaction was also performed under several other
reduction conditions: NaBH(OAc)3 ds (4R) = 90%, 76%;
NaBH4, ds (4R) = 95%, 88%; t-(BuO)3AlLiH, ds
(4R) = 99%, 87%.
(14) Treatment of monoacid 16 and diacid 18 with diazomethane
in Et2O afforded the corresponding cis and trans
diastereomeric methyldiesters that could be easily
differentiated by NMR spectroscopy [cis-isomer, d = 3.67
(CO2Me), 3.01 (H1, H2) ppm; trans-isomer: d = 3.70
(CO2Me), 3.39 (H1 or H2), 3.15 (H1 or H2) ppm].
(15) Fukuyama, T.; Lin, S.-C.; Li, L. J. Am. Chem. Soc. 1990,
112, 7050.
(16) Evans, D. A.; Willis, M. C.; Johnston, J. N. Org. Lett. 1999,
1, 865.
(17) Takai, K.; Nitta, K.; Utimoto, K. J. Am. Chem. Soc. 1986,
108, 7408.
(18) Evans, D. A.; Black, W. C. J. Am. Chem. Soc. 1993, 115,
4497.
(19) Preparation of Methyl (1R,2R,4S)-2-[(E)-2-Iodovinyl]-4-
(methoxymethoxy)cyclopentanecarboxylate (4)
To a suspension of anhyd CrCl2 (1 g, 8.1 mmol) in anhyd and
Synlett 2008, No. 3, 389–393 © Thieme Stuttgart · New York