Accelerating effect induced by the structure of alpha-amino acid in the copper-catalyzed coupling reaction of aryl halides with alpha-amino acids. Synthesis of benzolactam-V8

The coupling of optically pure alpha-amino acids with aryl halides produces enantiopure N-aryl-ccamino acids with retention of configuration under the catalysis of CuI. This reaction can complete at much lower temperature tha n typical Ullmann condensation even for electron-rich aryl halides, which i ndicates that an accelerating effect induced by the structure of the alpha- amino acid exists in this reaction, alpha-Amino acids with larger hydrophob ic groups give higher coupling yields, while those with smaller hydrophobic groups only deliver lower yields and no coupling products were detected fo r those with hydrophilic groups. No racemization was observed in most cases of this coupling reaction. After some controlled experiments, a possible m echanism including the pi-complex and the intramolecular substitution-react ion is proposed. Based on this catalyzed reaction, a facile and stereoselec tive-synthesis of benzolactam-V8, a new PKC activator, is achieved.