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

Abstract

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).