the way the lithiated oxazolinyloxirane 2e and the nitrone
3a interact with each other. It is worth pointing out that the
configuration at the C-3 of (+)-4i was ascertained to be
opposite (R) to that for the starting oxazolinyloxirane (S,S)-
(-)-1e,14 indicating that an inversion had occurred at this
carbon.15
Configuration of the three newly created stereogenic
centers is presumably established in the transition state TS-2
(Scheme 4) that results from the nucleophilic addition of the
lithiated oxirane 2e on the re face of 3a. To justify such a
transition state we assume that the lithiated oxiranes (S,S)-
2e-Li and (S,R)-2e-Li14 interconvert; then, the diastereomeric
lithiated oxirane (S,R)-2e-Li (having the isopropyl group on
the C-4 of the oxazoline ring far away from the oxirane C-Li
bond) preferentially reacts with the nitrone for experiencing
a lower steric hindrance to produce (3R,4R,7S,11S)-(+)-4i.
Treatment of (+)-4i with aq oxalic acid afforded optically
active 5-isoxazolidinone (+)-5a highly enantioenriched (ee
> 99%) and in good yield (76%).
quantitatively reduced to the corresponding epoxyamino acid
(+)-8a (ee > 99%, [R]D +9).
In conclusion, this paper describes how novel dispirocyclic
compounds such as 4, epoxy-isoxazolidinones 5, and R-epoxy-
â-amino acids 8, all never reported before, can simply and
highly stereoselectively be obtained just by combining the
chemistry of lithiated oxazolinyloxiranes with that of ni-
trones.
Acknowledgment. This work was carried out under the
framework of the National Project “Stereoselezione in Sintesi
Organica, Metodologie ed Applicazioni” and the FIRB
Project “Progettazione, preparazione e valutazione biologica
e farmacologica di nuove molecole organiche quali potenziali
farmaci innovativi” supported by the Ministero dell’Istruzione,
dell’Universita` e della Ricerca (MIUR, Rome) and by the
University of Bari and CNR (Rome). We are also grateful
to Prof. Marcel Pierrot of the Centre Scientifique Saint-
Jerome, Marseille, France, for performing X-ray analysis on
compounds (()-4a and (+)-4i.
Similarly, lithiation of oxazolinyloxirane (R,R)-(+)-1e (dr
98/2, ee > 99%, [R]D +79) (Scheme 5) followed by the
addition of 3a furnished, via (3S,4S,7R,11R)-(-)-4i, the
enantiomeric 5-isoxazolidinone (-)-5a in high optical purity
(ee > 99%, [R]D -82) and good yield (60%). This could be
Supporting Information Available: Spectroscopic and
physical data for compounds (+)/(-)-1e, 4a-h, 5a-d, 6,
7, and 8a-d, and crystallographic data for (()-4a and (+)-
4i. This material is available free of charge via the Internet
(12) The (S,S) absolute configuration of the major diastereomer of
oxazolinyloxirane (-)-1e (dr 98/2) was deduced by combining the results
of a 2D-NOESY Phase-Sensitive experiment and calculations (see Sup-
porting Information) and was in agreement with what reported for other
optically active oxazolinyloxiranes prepared as just described for (-)-1e
(see ref 13).
OL034927Q
(15) Concerning the configurational stability of oxiranyllithiums and their
synthetic applications see: (a) Satoh, T. Chem. ReV. 1996, 96, 3303-3325.
(b) Mori, Y. ReV. Heteroatom Chem. 1997, 17, 183-211. (c) Alickmann,
D.; Frohlich, R.; Wurthwein, E.-U. Org. Lett. 2001, 3, 1527-1530. (d)
Dechoux, L.; Agami, C.; Doris, E.; Mioskowski, C. Eur. J. Org. Chem.
2001, 4107-4110. (e) Hodgson, D. M.; Gras, E. Synthesis 2002, 12, 1625-
1642. (f) Yamauchi, Y.; Katagiri, T.; Uneyama, K. Org. Lett. 2002, 4, 173-
176. (g) Mori, Y.; Takase, T.; Noyori, R. Tetrahedron Lett. 2003, 44, 2605-
2608.
(13) Capriati, V.; Florio, S.; Luisi, R. Eur. J. Org. Chem. 2001, 2035-
2039.
(14) That an equilibrium between the two lithiated diastereomeric species
(S,S)-2e-Li and (S,R)-2e-Li may occur, as shown in Scheme 5, was proved
by the following experiment: when (S,S)-(-)-1e (dr 98: 2, ee > 99%)
was lithiated with s-BuLi/TMEDA at -98 °C and the resulting mixture
quenched after a few minutes with a D+ source, an almost 1:1 mixture of
(S,S)-1e and (S,R)-1e (both 95% D) was obtained.
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Org. Lett., Vol. 5, No. 15, 2003