New Synthetic Technology for Efficient Construction of α-Hydroxy-β-amino Amides via the Passerini Reaction1

The Passerini reaction of N-protected amino aldehydes, isonitriles, and TFA using pyridine-type bases proceeds under mild conditions and directly affords α-hydroxy-β-amino amide derivatives in moderate to high yields. These adducts are readily hydrolyzed to α-hydroxy-β-amino carboxylic acids. Application of these key intermediates to concise syntheses of P1-α-ketoamide protease inhibitors is illustrated.