Persulfate-Mediated Oxidative C−H Functionalization of Glycinates to Access Diverse Unnatural Amino Acids

We have developed an operationally simple and green approach to prepare robust α-alkyl unnatural amino acids through the dual oxidative activation of glycine derivatives and alkylcarboxylic acids with persulfate as the sole oxidizing agent. This method allows for the utilization of naturally abundant alkylcarboxylic acids as radical sources without the assistance of catalysts. Notably, this method allows for the late-stage decoration of biologically relevant carboxylic acids and peptides to construct diverse unnatural amino acids. In addition, the generality of the oxidative activation method enables a facile synthetic approach to α-phosphonyl glycine derivatives by using phosphites and phosphine oxides.