Efficient synthesis of fluorinated α- and β-amino nitriles from fluoroalkylated α,β-unsaturated imines

• Published in: Tetrahedron 2011-02, Vol.67 (8), p.1575-1579
• Main Authors: Palacios, Francisco, Ochoa de Retana, Ana M., Pascual, Sergio, Fernández de Trocóniz, Guillermo
• Format: Article
• Language: English
• Subjects: Acetonitrile; Aliphatic compounds; Chemistry; Cyanides; Derivatives; Exact sciences and technology; Fluorinated α and β-amino nitriles; Fluorinated α,β-unsaturated imines; Fluoroalkylated enamines; Hydrolysis; Imines; Nitriles; Organic chemistry; Phosphorylated enamines; Preparations and properties; Synthesis (chemistry); Tetrahedrons; β-Amino acid derivatives
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2010.12.046

A simple and efficient synthesis of fluoroalkylated α-amino nitrile ( 4) derivatives by regioselective 1,2-addition of trimethylsilyl cyanide to fluoroalkylated α,β-unsaturated imines ( 1) is described. Fluoroalkylated β-amino nitriles ( 7) are also prepared by regioselective 1,2-addition of α-carbanions derived from acetonitrile to fluoroalkylated α,β-unsaturated imines ( 1). Fluoroalkylated α-( 4) and β-amino nitriles ( 7) are also prepared through an ‘one pot’ procedure by reaction of enaminophosphonate 2 with BuLi, addition of aldehydes and subsequent addition of either trimethylsilyl cyanide or α-carbanion derived from acetonitrile. Basic hydrolysis of α-( 4) and β-amino nitriles ( 7) gives fluoroalkylated α-( 5) and β-amino acids ( 8). [Display omitted]