Functionalization of (2S)‐Isopropyl‐5‐iodo‐2,3‐dihydro‐4(H)‐pyrimidin‐4‐ones by a Suzuki–Miyaura Cross‐Coupling Reaction Using Aryltrifluoroborate Salts: Convenient Enantioselective Preparation of α‐Substituted β‐Amino Acids

Abstract

AbstractA simple protocol for the Pd(OAc)2‐catalyzed cross‐coupling reaction of 1‐benzoyl‐(2S)‐isopropyl‐5‐iodo‐2,3‐dihydro‐4(H)‐pyrimidin‐4‐ones with potassium aryltrifluoroborates was developed. The reaction is performed at 110 °C with a ligand‐free catalyst. In all cases, complete conversion of the 1‐benzoyl‐(2S)‐isopropyl‐5‐iodo‐2,3‐dihydro‐4(H)‐pyrimidin‐4‐onesand aryltrifluoroborates into the C–C coupling products was observed within 30–360 min. It is noteworthy that a largevariety of groups present in the potassium aryltrifluoroborates (–CF3, –OMe, –SEt, –CN, –CHO, –Cl, –Cbz, –NCbz,–OH, –CO2H) could be tolerated. Hydrogenation of the endocyclic double bonds in the Suzuki–Miyaura products followed by acid hydrolysis afforded highly enantioenrichedα‐aryl‐substituted β‐amino acids.