412
considerations suggest that quinoxaline alters the rate-determining step by dropping
the activation energy of the Pd
II
to Pd
IV
oxidation step leading to greater formation
of the desired fluorinated product. Remarkably, the prerequisite of an external
ligand can be circumvented when quinoxaline is used as the directing group in the
palladium- catalyzed fluorination reaction (Scheme 53) [109].
Independent research in this line unveils that palladium-catalyzed site- and diastereoselective β-fluorination of α-amino acids can be achieved by employing
2-(pyridine-2-yl)isopropyl amine (PIP) as the chelating directing group. Both benzylic and methylene C–H bonds of α-amino acids were regiospecifically converted
into the corresponding β-fluorinated product in satisfactory synthetic yields (Scheme
54) [110, 111].
Scheme 52 8-Aminoquinoline-directed b-fluorination of C(sp
3
)–H bonds
Scheme 53 Quinoxaline-directed β-fluorination of carboxamides
Scheme 51 Mono- and bis-chlorination using 8-aminoquinoline directing group
A. Gupta et al.