In particular, when R1 is an aromatic substituent, a ring-
opening reaction occurs, mainly at the 3-position (benzylic
position) of the aziridine ring.5 On the other hand, oxazoline-
5-carboxylate can be a useful intermediate as the synthetic
equivalent of an R-cation for the preparation of R-substituted
â-amino esters. Unlike oxazoline-4-carboxylate, we found
that oxazoline-5-carboxylates were utilized by many groups,6
but mainly as an intermediate for N-benzoyl-(2R,3S)-3-
phenylisoserine, a taxol C-13 side chain. Herein, we report
an efficient synthesis of both cis- and trans-oxazoline-5-
carboxylates as well as their ring-opening reactions.
sulfonate 3 with DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)
in refluxing chloroform for 1 h gave trans-oxazoline 5 with
net retention of configuration in 76% yield with a trace of
cis-oxazoline 4, which can be removed by column chroma-
tography. Epimerizations of cis-oxazoline-4-carboxylate or
cis-imidazoline to its thermodynamically more stable trans-
isomer using triethylamine were reported very recently.8,3c
However, in our case, we did not observe any epimerization
from cis-oxazoline to trans-oxazoline in refluxing chloroform
in the presence of DBU. We believe epimerization of 3 to
anti methanesulfonate occurred first, then trans-oxazoline
was obtained from this intermediate. The NMR spectra of
the cis-isomer 4 and the trans-isomer 5 showed a distinct
difference in the coupling constants. The coupling constant
between H-4 and H-5 for the cis-isomer 4 was 10.8 Hz and
that for the trans-isomer 5 was 6.8 Hz.
Commercially available isopropyl trans-cinnamate (1) was
the starting point of our synthesis (Scheme 1). Amino alcohol
Scheme 1
Ring-opening reactions of trans- and cis-oxazoline-5-
carboxylates are summarized in Table 1. When trimethylsilyl
Table 1. Ring-Opening Reaction of trans- and
cis-Oxazoline-5-carboxylates (5, 4)
2 was obtained in 81% yield following the reported Sharpless
AA reaction.7 Amino alcohol 2 was then converted to its
methanesulfonate 3, which was successfully transformed to
cis-oxazoline 4 with a clean inversion of configuration at
the R-center in 62% yield with potassium bicarbonate in
acetone-water. On the other hand, treatment of methane-
azide was used as an azide source for the synthesis of the
R,â-diamino acid derivative, we found that there were huge
differences in reactivity between the trans- and cis-oxazoline
compounds. Treatment of trans-oxazoline 5 with trimethyl-
silyl azide in methanol at 70-80 °C led to the trans-azide 6
in 90% yield. However, even at higher reaction temperature
or in the presence of additional Lewis acid such as boron
trifluoride diethyl etherate (Et2O‚BF3) or trimethylsilyl triflate
(TMSOTf), only unreacted cis-oxazoline 4 was recovered
in an attempt to open this oxazoline ring with trimethylsilyl
(5) (a) Papa, C.; Tomasini, C. Org. Lett. 1999, 1, 2153. (b) Tanner, D.
Angew. Chem., Int. Ed. Engl. 1994, 33, 599.
(6) (a) Gou, D.-M.; Liu, Y.-C.; Chen, C.-S. J. Org. Chem. 1993, 58,
1287. (b) Kingston, D. G. I.; Chaudhary, A. G.; Gunatilaka, A. A. L.;
Middleton, M. L. Tetrahedron Lett. 1994, 35, 4483. (c) Bunnage, M. E.;
Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1993, 1375.
(d) Chen, S.-H.; Farina, V.; Vyas, D. M.; Doyle, T. W.; Long, B. H.;
Fairchild, C. J. Org. Chem. 1996, 61, 2065.
(7) Bruncko, M.; Schlingloff, G.; Sharpless, K. B. Angew. Chem., Int.
Ed. Engl. 1997, 36, 1483.
(8) Hayashi, T.; Kishi, E.; Soloshonok, V. A.; Uozumi, Y. Tetrahedron
Lett. 1996, 37, 4969.
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Org. Lett., Vol. 2, No. 9, 2000