Truncated diastereoselective Passerini reaction, a rapid construction of polysubstituted oxazole and peptides having α-hydroxy-β-amino acid component

The reaction of aldehydes and ketones, including aliphatic and aromatic ones, with amides of alpha-isocyano-beta-phenylpropionic acid in toluene in the presence of lithium bromide gives 2,4,5-trisubstituted oxazoles in good to excellent yield. Protected chiral alpha-amino aldehydes participate in this reaction to give, after hydrolysis of the oxazoles, norstatine-containing peptides in good overall yield. The nucleophilic addition of isonitriles to N,N-dibenzyl phenylalanal is investigated for the first time and is found to be stereoselective leading predominantly to the anti-adduct (dr=9/1). On the other hand, the reaction between the N-Boc phenylalanal and isonitrile is non-stereoselective. (C) 2004 Elsevier Ltd. All rights reserved.