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

✍ Scribed by Hélio A. Stefani; Monica F. Z. J. Amaral; Gloria Reyes-Rangel; Jorge Vargas-Caporali; Eusebio Juaristi

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 565 KB
• Volume: 2010
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.201000852

✦ Synopsis

Abstract

A simple protocol for the Pd(OAc)~2~‐catalyzed cross‐coupling reaction of 1‐benzoyl‐(2__S__)‐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‐(2__S__)‐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 (–CF~3~, –OMe, –SEt, –CN, –CHO, –Cl, –Cbz, –NCbz,–OH, –CO~2~H) 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.