A Long Journey to the Unknown Chemical Space: Synthesis of Ferrocene 1,3-Derivatives by Distal C-H Activation by a Template Approach

Reaching the unreachable! Ferrocene derivatives have found wide applications as ligands, catalysts, functionalized materials, fuel additives, agrochemicals, drugs and many bioorganometallic compounds. Planar chiral ferrocene derivatives are bench-mark ligands used in asymmetric catalysis both in bulk chemical industry and fine chemical synthesis. Traditionally, ferrocene-1,2-derivatives were prepared by lithiation-electrophilic quenching protocol, which is still being pursued, until recently when transition-metal catalyzed C-H activation came into play. But till date, the third position of Cp ring of ferrocene remained as hitherto inaccessible chemical space for the direct functionalization in the ferrocene and bypassing the active second position is most challenging task and beyond common comprehension. Here we report the regiospecific 1,3functionalization of ferrocene via covalently bound pyridine containing template directed approach with precise selectivity under Pd(II)/MPAA catalytic system. The process shows broad scope in olefins with ferrocenylmethylamine in moderate to good yields via highly strained 12-membered macrocyclophane-like pre-transition state with appended ferrocene. We believe that this result will pave the way towards the development of novel class of ferrocene pincer ligands that would be an addition to the repertoire of toolbox of ligands available for synthetic organic chemist.