Asymmetric synthesis of (S)-1-aminoindan-1,5-dicarboxylic acid and related analogues via intramolecular acylation of enantiopure α,α-disubstituted amino acids

α,α-Disubstituted amino acid derivatives are synthesized either by a self-regeneration of stereocenter strategy or using the asymmetric Strecker reaction/alkylation method. Of the four types of substrates tested for intramolecular acylation, those with a 4-alkoxyl group do not react, those with a 4-bromo substituent give lower conversions, while those without a 4-substituent or with a 4-methyl group work well to give the desired cyclization products. Based on these investigations, a new route for preparing (S)-1-aminoindan-1,5-dicarboxylic acid (S)-AIDA and its analogues was developed.