Regioselective catalytic transformation of carbon-hydrogen bonds to other functional groups represents a long-standing challenge in homogeneous and heterogeneous catalysis. The Ir-catalyzed C-H activation/borylation has emerged as a useful method for synthesizing various aryl and heteroaryl boronic esters with regiochemistry complimentary to traditional methods and tolerant of various functional groups. The steric dominance of C-H activation/borylation has allowed for the synthesis of new aromatic building blocks which were previously unaccessible or hard to synthesize.With the aid of high throughput experimentation (HTE), we designed reaction screens that would not only optimize Ir-catalyzed C-H borylation reactions for more challenging substrates, but also broaden the scope of this chemistry by assessing the efficiency and compatibility of the reactions as functions of precatayst, boron reagent, ligand, order of addition, temperature, solvent and substrate.We then sought to apply these results to unprotected anilines which were inert under conventional Ir-catalyzed C-H borylation conditions. Building off a recent report from our research group that utilized a unique outer sphere directing effect to obtain ¬ortho¬ functionalized C-H borylation products from NBoc protected anilines, we investigated whether we could use HBPin as a traceless protecting/directing group for the borylation of primary anilines under more forcing conditions. Our attempts were successful and provided for a one-pot protection/deprotection procedure that used a lower catalyst loading and gave products in better to comparable yields than the NBoc protected borylation reaction. Using an (η6-C6Me3H3)Ir(BPin)3 as starting material, five-coordinate bisphosphine complexes can be synthesized by displacement of the η6-C6Me3H3 with the incoming phosphine ligands. Using this method we have isolated the trans-Ir(PAr3F)2BPin3 complex which is thought to be the active catalyst for the ortho¬-C-H directed borylation of benzoate esters first discovered by Miyaura. The trans-Ir(PAr3F)2BPin3 complex is not catalytically competent with HBPin as borylating reagent. We have since been able to develop silylphosphine chelates (Figure 8) that are compatible with HBPin while retaining the unique selectivity shown with the Ir(PAr3F)2BPin3 complex. Studies to further improve on the silylphosphine ligand design and extend the substrate scope are ongoing.
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