Split cross-coupling via Rh-catalysed activation of unstrained aryl-aryl bonds

Constructive functionalization of unstrained aryl-aryl bonds has been a fundamental challenge in organic synthesis due to the inertness of these bonds. Here we report a split cross-coupling strategy that allows twofold arylation with diverse aryl iodides through cleaving unstrained aryl-aryl bonds of common 2,2 '-biphenols. The reaction is catalysed by a rhodium complex and promoted by a removable phosphinite directing group and an organic reductant such as tetrakis(dimethylamino)ethylene. The combined experimental and computational mechanistic studies reveal a turnover-limiting reductive elimination step that can be accelerated by a Lewis acid co-catalyst. The utility of this coupling method has been illustrated in the modular and simplified syntheses of unsymmetrical 2,6-diarylated phenols and skeletal insertion of phenylene units. Unstrained aryl-aryl bonds are among the most inert bonds in organic chemistry. Now the development of a split cross-coupling strategy enables the direct functionalization of such bonds through Rh-catalysed C-C cleavage and cross-coupling with aryl halides, providing a method for biaryl synthesis.