During the last few decades iridium catalyzed C–H borylations have become an important method to access aryl boronic esters. As aryl C–H borylations are governed predominately by sterics, this reaction offers a complementary regiochemical approach to traditional synthetic routes accessing aromatic boronic esters such as metal halogen exchange and Miyaura borylation. As these reactions can be reliably directed away from positions ortho to any functionality other than hydrogen, fluorine, and nitriles, iridium catalyzed borylations find ample use in industry and total synthesis. Since this reaction is directed sterically and not electronically, regiochemical selectivity can become challenging in cases where multiple activation sites are available, especially in the case of 1,2-disubstituted arenes. To overcome this challenge, we developed a method for para selective borylation of phenols and anilines utilizing alkyl ammonium cations as steric shields to direct borylation. We further show how this methodology can be expanded to utilize in situ heteroatom borylation in place of the alkyl ammonium cations to access the same para selectivity. We further utilized existing 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Bpin) functionalities to guide the regiochemistry of iridium catalyzed C–H borylation ortho to itself to access 1,2-diborylated arenes as well as new 1,2,3-triborylated arenes. As borylated compounds are important synthetic intermediates, being able to study C–H borylations mechanistically offers important insights into reactions utilizing these compounds. We therefore investigated developing a method to measure boron heavy atom isotope effects using fluorine reporters and NMR to observe boron isotopic distributions.
Read
