Duality of mechanism in the tetramethylfluoroformamidinium hexafluorophosphate-mediated synthesis of N-benzyloxycarbonylamino acid fluorides

In the tetramethylfluoroformamidinium-hexafluorophosphate mediated fluorination of Z-amino acids the occurrence of at least two concurrent pathways has been observed: the direct conversion of the activated intermediate into the product and the intramolecular cyclization to the corresponding oxazolone followed by fluoride nucleophilic ring opening. The contribution of the second process strongly depends on the nature of the amino acid, being absent in the natural amino acids while in the alpha-alkyl-alpha-methyl derivatives it parallels the steric bulkiness of the alkyl substituent (Me<i-Pr<t-Bu). The formation of the oxazolone with subsequent slow ring opening appears the main cause of the decreased reactivity towards fluorination of the alpha-alpha-disubstituted amino acids. Addition of “HF” species to the reaction mixture considerably accelerates the oxazolone ring opening process and therefore the formation of the alpha-alpha-disubstituted acyl fluorides