1,2-Asymmetric induction in dianionic functionalization reactions of L-aspartic acid diesters ¹

Abstract

Functionalization of the dianions derived from N-protected aspartic acid esters is a simple route to the preparation of novel α-amino acids and peptidomimetic precursors. We have demonstrated previously that high levels of 1,2-asymmetric induction may be obtained in this reaction under the appropriate conditions (I.B. Parr, et al., J. Med. Chem., 1996, 39, 2367). The observed diastereoselectivity results from the complicated interaction of a number of experimental factors. We now report that the nature of the electrophile and the work-up protocol both influence the level of stereocontrol in the alkylation of N-benzyloxycarbonyl aspartic acid esters. In addition, the stereochemical preference for high anti selectivity in the reaction can be reversed by increasing the steric bulk of the α-ester. Application of these observations has allowed the stereocontrolled preparation of two novel, N-protected, chimeric α-amino acids and a peptidomimetic precursor. The molecular basis for 1,2-asymmetric induction in the alkylation reaction can be rationalized on the basis of the configurational preferences of the lithium ester enolate formed from the N-protected aspartate diester used in these studies.

References

1. Presented in part at the 201st National Meeting of the American Chemical Society, Atlanta, GA, April 1991. Abstracts of Papers, ORGN-227.
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