Silver‐Catalyzed Three‐Component 1,1‐Aminoacylation of Homopropargylamines: α‐Additions for Both Terminal Alkynes and Isocyanides

The reaction of secondary homopropargylamines, isocyanides, and water in the presence of a catalytic amount of silver acetate and subsequent purification by chromatography on silica gel afforded substituted proline amides in good to excellent yields. Primary homopropargylamines underwent a cyclizative Ugi–Joullié three‐component reaction with isocyanides and carboxylic acids to afford functionalized N‐acyl proline amides. High diastereoselectivity was observed in the synthesis of 4‐alkoxy and 4,5‐disubstituted proline derivatives. This work represents the first examples of a three‐component cyclizative 1,1‐aminoacylation of terminal alkynes. No atom lost: Homopropargylamines react with isocyanides and either carboxylic acids or water in the presence of a catalytic amount of silver acetate to afford substituted proline amides. This three‐component reaction proceeds by a cyclizative 1,1‐aminoacylation of terminal alkynes and affords good to excellent yields. Boc=tert‐butoxycarbonyl.