of the improved results of entry 3 to attain 94% regios-
electivity, and 10a was isolated in 91% yield (entry 10).
Later, entry 10 was scaled up (40 mg to 1.5 g) in the
synthetic application to find similar efficiency. The copper
reagent with a different ratio (9/Cu(acac)2 = 2:1) was less
selective (entry 11). Reagents prepared from Cu(OAc) and
Cu(OAc)2 showed no reactivity toward the substitution
(data not shown).
To clarify the influence of the protective group in 3,
picolinates 10bꢀe were subjected to the substitution under
the optimized conditions (entry 10). The TES ether 3b
showed similar selectivity and reactivity (entry 12), whereas
TBDPS and Bn derivatives 3c,d produced 10c,d less effi-
ciently than 3a,b (entries 13,14). Acetate 3e gave a mixture of
unidentified products (entry 15).
coupling with p-MeC6H4I and (E)-I-CHdCH-Bu deliv-
ered 16 and 17 in good yields. During the transformations
neither allene nor diene byproducts were formed. Pre-
viously, compounds similar to 15ꢀ17 have been synthe-
sized bythe reaction ofcyclopentadiene monoepoxidewith
acetylides.10 However, the yields and selectivity are quite
low and, in addition, the monoepoxide is chemically highly
unstable. Thus, the present method is advantageous with
respect to selectivity and yield.
Scheme 2. Conversion of the TMS Acetylenes
We then applied the method to the cyclohexene derivative
4a, which upon reaction with 9/Cu(acac)2 in CH2Cl2/THF at
0 °C for 2 h afforded the SN20 product 12 with high product
selectivity and regioselectivity and in good yield (eq 1).
To investigate the synthetic potential of this substitu-
tion, the transformation of 10a shown in Scheme 2 was
investigated.9 Desilylation with K2CO3 in MeOH afforded
14 in 82% yield. Alkylation of 14 with C5H11I proceeded
cleanly to furnish 15 in 76% yield, while Sonogashira
(5) Sugai, T.; Mori, K. Synthesis 1988, 19–22.
Similarly, the TMS group was removed from 12 and the
resulting acetylene 18 was converted toalkylacetylene 19 in
55% yield over two steps (Scheme 2). A compound similar
to 19 was once synthesized by the epoxide opening of
cyclohexadiene monoepoxide and lithium acetylides.11
We then studied the synthesis of the PGF2R intermediate
26, which was previously synthesized by Stork as a diaster-
eomeric mixture via the epoxide ring opening of racemic
cyclopentadiene monoepoxide with the lithium acetylide
generated from the propargylic alcohol derivative.10a
Probably due to the reasons mentioned above and/or lack
of an efficient method for obtaining the optically active
epoxide with a reasonable yield and high % ee,12 the
intermediate has been left obscurely in the community of
(6) (a) Myers, A. G.; Hammond, M.; Wu, Y. Tetrahedron Lett. 1996,
37, 3083–3086. (b) Myers, A. G.; Glatthar,R.;Hammond,M.;Harrington,
P. M.; Kuo, E. Y.; Liang, J.; Schaus, S. E.; Wu, Y.; Xiang, J.-N. J. Am. Chem.
Soc. 2002, 124, 5380–5401.
(7) The trans stereochemsitry of 10a was determined by converting to
14 (Scheme 2) and then to i, which was identical by 1H NMR spectro-
scopy with that derived from known alcohol iii.7a,b The low yields were
probably due to high volatility. (a) Ito, M.; Matsuumi, M.; Murugesh,
M. G.; Kobayashi, Y. J. Org. Chem. 2001, 66, 5881–5889. (b) Schneider,
C.; Brauner, J. Eur. J. Org. Chem. 2001, 4445–4450.
(10) (a) Stork, G.; Isobe, M. J. Am. Chem. Soc. 1975, 97, 4745–4746.
(b) Crosby, G. A.; Stephenson, R. A. J. Chem. Soc., Chem. Commun.
1975, 287–288. (c) Bradbury, R. H.; Walker, K. A. M. J. Org. Chem.
1983, 48, 1741–1750. (d) Briggs, A. J.; Walker, K. A. M. J. Org. Chem.
1990, 55, 2962–2964.
(8) (a) Goering, H. L.; Tseng, C. C. J. Org. Chem. 1983, 48, 3986–
3990. (b) Underiner, T. L.; Paisley, S. D.; Schmitter, J.; Lesheski, L.;
Goering, H. L. J. Org. Chem. 1989, 54, 2369–2374 and references cited
therein.
(11) Alexakis, A.; Vrancken, E.; Mangeney, P.; Chemla, F. J. Chem.
Soc., Perkin Trans. 1 2000, 3352–3353.
(12) (a) Mikane, D.; Hamada, T.; Irie, R.; Katsuki, T. Synlett 1995,
827–828. (b) Chang, S.; Heid, R. M.; Jacobsen, E. N. Tetrahedron Lett.
(9) Allylic substitution of 3a with RCtCMgBr (R = C5H11, Ph) and
Cu(acac)2 was unsuccessful.
1994, 35, 669–672. (c) Zaidlewicz, M.; Krzemı
1996, 37, 7131–7134.
´
nski, M. Tetrahedron Lett.
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