Palladium‐Catalyzed Asymmetric Decarboxylative Allylation of Azlactone Enol Carbonates: Fast Access to Enantioenriched α‐Allyl Quaternary Amino Acids

• Published in: European journal of organic chemistry 2019-01, Vol.2019 (4), p.732-741
• Main Authors: Serra, Massimo, Bernardi, Eric, Marrubini, Giorgio, De Lorenzi, Ersilia, Colombo, Lino
• Format: Article
• Language: English
• Subjects: Allyl compounds; Allylation; Amino acids; Aromatic compounds; Asymmetric catalysis; Asymmetric synthesis; Carbonates; Chemical reactions; Enantiomers; Palladium; Quaternary amino acids; Recrystallization
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201801363

We report a fast protocol for the synthesis of enantioenriched quaternary 4‐allyl oxazol‐5‐ones. The key step is a Pd‐catalyzed enantioselective Tsuji allylation of azlactone allyl enol carbonates, which can be easily prepared starting from racemic α‐amino acids. The use of (R,R)‐DACH‐phenyl Trost chiral ligand allowed the attainment of the allylated derivatives in very good yields (83–98 %) and with ee up to 85 %. Scaling up the allylation protocol to gram quantities did not affect the yields end ee values. The produced 4‐allyl azlactones can be converted into the corresponding quaternary amino acids or submitted to further synthetic elaborations exploiting the allyl moiety as a handle for the attachment of alkyl and aryl groups. After hydrolysis of the azlactone ring, the zwitterionic amino acids can be attained in enantiopure or nearly optically pure form through only one recrystallization step. A practical synthetic protocol for the preparation of enantioenriched 4‐allyl oxazol‐5‐ones was developed. The key Pd‐catalyzed decarboxylative allylation allowed the attainment of the allylated derivatives in very good yields (83–98 %) and with ee up to 85 %. The corresponding quaternary amino acids can be recovered in their enantiopure form or in high optical purity after a single recrystallization step.