658
without any detectable racemization. An efficient resolution is obtained with five equivalents of t-BuOK
(entry 4). If only three equivalents of base are used, the reaction is slower and a small part of ester 1 (2R)
is hydrolyzed (entry 3). If the oxygen of the side chain is sterically crowded (entry 7) or absent (entry 8),
the resolution is incomplete.
These results suggest that the tetrahedric intermediate as proposed by Gassman and co-workers is
probably better stabilized in the case of diastereomer 1 (2S) as compared to the diastereomer 1 (2R) and
leads to differences in the ester cleavage and thereby kinetic resolution.
In summary, we presented here a cleavage of sterically crowded α- and β-aminoesters, using non-
aqueous conditions. We established a stereoselective accelerating effect of a neighboring heteroatom in
the deprotection procedure. This effect was used for the preparation of optically pure aziridine ester 1
(2R) and acid 1 (2S) through an efficient kinetic resolution. This method is of particular interest for the
preparation of the above mentioned aziridines whose use in asymmetric synthesis is under investigation
in our laboratory.
Acknowledgements
One of us (V.A.) thanks MENRT for a grant.
References
1. Alezra, V.; Bonin, M.; Micouin, L.; Husson, H.-P. Tetrahedron Lett., 2000, 41, 651.
2. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd Ed; Wiley: New York, 1981.
3. Gassman, P. G.; Schenk, W. N. J. Org. Chem. 1977, 42, 918.
4. Unlike the Gassman standard procedure, no additional amount of water was needed to perform the reaction. We assume that
moisture present in the solvent and in unsublimed potassium t-butoxide is enough to provide the KOH equivalent needed for
the first step of the deprotection.
5. Typical procedures: (a) Deprotection of compound 4: To a solution of aminoester 4 (200 mg, 0.9 mmol) in THF (10 mL) was
added t-BuOK (203 mg, 1.8 mmol) at 0°C. Saturated NH4Cl aqueous solution (1 mL) was added after 1 h and the solvent was
subsequently evaporated. The crude mixture was dissolved in a small amount of water, neutralized by an HCl 1N solution and
concentrated. The crude mixture was triturated in MeOH and the solvent was evaporated to give 122 mg of amino acid (82%).
(b) Kinetic resolution of esters 1: To an equimolar solution of aziridines 1 (2R) and 1 (2S) (150 mg, 0.54 mmol) in THF (10
mL) was added t-BuOK (304 mg, 2.70 mmol) at −20°C. After 1 h was added a small amount of a saturated NH4Cl aqueous
solution, the mixture was dried on magnesium sulfate and filtrated. THF was evaporated, the crude product was dissolved in
a mixture of H2O/CH2Cl2 and extracted three times with CH2Cl2. The organic phases were combined, dried and evaporated
to give ester 1 (2R) as an oil (75 mg, 50%). The aqueous phase was treated as described for compound 3 (see Ref. 5a) to give
acid 1 (2S) as its potassium salt (67 mg, 48%). 1 (2R).
6. ‘Classical’ saponification (KOH, H2O, THF) of this compound required 24 h for completion.
7. (a) Chung, S.-K.; Kang, D.-H. Tetrahedron: Asymmetry 1997, 8, 3027. (b) Reetz, M. T. Angew. Chem., Int. Ed. Engl. 1991,
30, 1531.
8. Gassman, P. G.; Hodgson, P. K. G.; Balchunis, R. J. J. Am. Chem. Soc. 1976, 98, 1275.
9. These compounds were prepared according to a reported procedure. (a) Harada, K.; Nakamura, I. J. Chem. Soc., Chem.
Commun. 1978, 522. (b) Häner, R.; Maetzke, T.; Seebach, D. Helv. Chim. Acta 1987, 70, 1676.