Complementary site-selectivity in arene functionalization enabled by overcoming the ortho constraint in palladium/norbornene catalysis.

Achieving site-selectivity in arene functionalization that is complementary to the site-selectivity from electrophilic aromatic substitution reactions has been a long-standing quest in organic synthesis. Palladium/norbornene cooperative catalysis potentially offers a unique approach to this problem, but its use has been hampered by the ortho constraint, which is the requirement of an ortho substituent for mono ortho functionalization of haloarenes. Here, we show that such a challenge could be addressed using a new class of bridgehead-modified norbornenes, thereby enabling a broadly useful strategy for arene functionalization with complementary site-selectivity. A range of ortho-unsubstituted aryl iodides, previously problematic substrates, can now be employed to provide mono ortho-functionalized products effectively. This method is applicable for late-stage functionalization of complex bioactive molecules at positions that are difficult to reach by conventional approaches.