252637-90-4Relevant articles and documents
Flow synthesis of fluorinated α-amino acids
Vukelic, Stella,Ushakov, Dmitry B.,Gilmore, Kerry,Koksch, Beate,Seeberger, Peter H.
supporting information, p. 3036 - 3039 (2015/05/13)
Fluorinated α-amino acids are versatile compounds that are used for many purposes in medicinal and biochemistry. However, their synthesis remains a significant hurdle, often requiring multiple steps, multiple protecting groups, and/or the use of highly toxic reagents. These challenges have limited the application of fluorinated α-amino acids. A convenient, protecting-group-free and semi-continuous process for the synthesis of racemic fluorinated α-amino acids from fluorinated amines is described. Following a singlet-oxygen-driven photooxidative cyanation, an acid-mediated hydrolysis of the intermediate α-amino nitrile yields the desired α-amino acid. Aliphatic, benzylic, and homobenzylic residues with different fluorination degrees are tolerated, providing good overall yields (50-67?%). This semi-continuous process is particularly advantageous for an aliphatic amine, the intermediate α-amino nitrile of which decomposes upon isolation. An efficient, semi-continuous, and protecting-group-free method for the synthesis of fluorinated α-amino acids from the corresponding amines has been developed. A low temperature photooxidative cyanation of benzylic and aliphatic amines provided α-amino nitriles with varying fluorination patterns. These unstable intermediates were trapped with an acid-mediated hydrolysis with good overall yields.
