Synthesis of Ferrocene 1,3-Derivatives by Distal C-H Activation

The third position of cyclopentadienyl ring of a monosubstituted ferrocene has remained as an inaccessible chemical space for direct functionalization. Until recently, functionalizing the C(3)-position while bypassing the predominantly active C(2)-position is the most challenging task. Herein, we report a distal C-H functionalization of monosubstituted ferrocenes using an easily removable directing group with precise site-selectivity, under a Pd-II/ mono-N-protected amino-acid ligand catalytic system. The robust synthetic protocol leads to the synthesis of ferrocene 1,3-derivatives with broad scope in olefins while functionalizing ferrocenyl methylamine in moderate to good yields via a highly strained ferrocene appended 12-membered palladacycle intermediate.

Automated summary

In this study, a method for distal C-H functionalization of monosubstituted ferrocenes using an easily removable directing group under a Pd-II/ mono-N-protected amino-acid ligand catalytic system is reported. The synthetic protocol allows for the synthesis of ferrocene 1,3-derivatives with broad scope in olefins, by functionalizing ferrocenyl methylamine in moderate to good yields through a highly strained ferrocene appended 12-membered palladacycle intermediate.