THE ASYMMETRIC-SYNTHESIS OF ALPHA-AMINO-ACIDS - ELECTROPHILIC AZIDATION OF CHIRAL IMIDE ENOLATES, A PRACTICAL APPROACH TO THE SYNTHESIS OF (R)-ALPHA-AZIDO AND (S)-ALPHA-AZIDO CARBOXYLIC-ACIDS

Two complementary approaches to the asymmetric synthesis of α-amino acids have been achieved. In the initially investigated reaction sequence, the diastereoselective bromination of the illustrated boron enolate with N-bromosuccinimide was followed by stereospecific azide displacement by tetramethylguanidinium azide. The resulting α-azido carboximides may be readily purified to high diastereomeric purity by chromatography on silica.[inline formula omitted] In the second reaction sequence, the illustrated potassium enolate was treated with 2,4,6-triisopropylbenzenesulfonyl azide, and the intermediate sulfonyl triazene was decomposed through an acetic acid quench to give the α-azido carboximide. The diastereoselection of the reaction as a function of R is as follows: R = Me, CH2Ph, 97:3; R = CHMe2, 98:2; R = CMe3, >99:1; R = Ph, 91:9. The important parameters of this azidation process were evaluated, and experiments were conducted to help elucidate the mechanism of the reaction.[inline formula omitted] The α-azido carboximide products have been shown to be versatile α-amino acid synthons that may be readily converted to α-amino acids as well as to N-protected α-amino acid derivatives. The racemization-free removal of the chiral auxiliary was achieved in high yield both by saponification and transesterification, either before or after reduction and acylation of the azide functionality. © 1990, American Chemical Society. All rights reserved.