We are engaged in the systematic efforts to exploit new, efficient, and broadly useful palladium/norbornene (Pd/NBE) catalysis for site-specific arene mono- and di-functionalization. Our objective in the proposed funding period includes: first to develop new classes of vicinal di- functionalization, e.g. ortho amination, acylation, thiolation and annulation with epoxides by discovering new classes of electrophiles; and second to address the ?ortho effect? limitation (requirement of a pre-existing ortho substituent) by developing new NBE-type ligands. The proposed research is expected to vastly expand the toolbox for arene functionalization via site- specifically installing functional groups at unactivated positions, which in turn would streamline synthesis of complex biologically important molecules containing multi-substituted aromatic scaffolds.
Poly-substituted arenes and heteroarenes are ubiquitous in pharmaceuticals and approved drugs; however, the efficiency of using conventional approaches to access these structural motifs remains to be improved. The outlined proposal aims to enable new efficient catalytic methods for direct preparation of poly-substituted arenes and heteroarenes from readily available feedstocks. Success of the proposed research would significantly expedite the synthesis of complex aromatic molecules, which, in turn, would ultimately accelerate drug discovery.