Synthesis of complex unnatural fluorine-containing amino acids

The area of fluorinated amino acid synthesis has seen rapid growth over the past decade. As reports of singly fluorinated natural amino acid derivatives have grown, researchers have turned their attention to develop methodology to access complex proteinogenic examples. A variety of reaction conditions have been employed in this area, exploiting new advances in the wider synthetic community such as photocatalysis and palladium cross-coupling. In addition, novel fluorinated functional groups have also been incorporated into amino acids, with SF_X and perfluoro moieties now appearing with more frequency in the literature. This review focuses on synthetic methodology for accessing complex non-proteinogenic amino acids, along with amino acids containing multiple fluorine atoms such as CF₃, SF₅ and perfluoroaromatic groups.