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Highly Diastereoselective Mannich-Type Reactions of Chiral N-Acylhydrazones

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journal contribution
posted on 09.07.2004, 00:00 by Mikkel F. Jacobsen, Liviu Ionita, Troels Skrydstrup
The Lewis acid-mediated addition of silyl enolates to easily accessible homochiral N-acylhydrazones derived from 3-amino-2-oxazolidinones proceeded in yields up to 71% and diastereomeric ratios of 99:1. In most cases, optimal reaction conditions entailed the simple use of ZnCl2 in acetonitrile at room temperature. Hydrazones derived from phenyl-, isopropyl-, and benzyl-substituted 2-oxazolidinones were examined in the reaction in terms of yield and diastereoselectivity. The facile SmI2-mediated N−N bond cleavage of the formed hydrazines was demonstrated yielding a β-amino acid derivative. Hence, the overall reaction sequence constitutes an efficient asymmetric Mannich-type reaction. The sense of diastereoselectivity was explained by a preferential attack on the less shielded Si face of the chiral hydrazones and confirmed by means of X-ray crystallography.