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.The compatibility with Boc protecting groups allows for manipulating the regioselectivities for Ir–catalyzed borylations of nitrogen heterocycles. In addition, Ir–catalyzed borylations of protected amino acids are shown to be feasible for the first time, which augurs favorably for similar functionalizations of peptides. This work also established heat as a clean agent for Boc deprotection of BPin substituted heteroarenes.The halogen tolerance that is a hallmark of Ir C—H borylation makes it trivial to construct building blocks possessing halogen and boronate ester functionality. This unique feature of C—H borylation in combination with Suzuki coupling has allowed the synthesis of 2,3–diaryl and 3,5–diaryl thiophenes. DuP 697 a COX–2 inhibitor was synthesized in 5–steps with an overall 42% yield.Even though protolytic deborylation is an undesired side reaction in most coupling reactions, it was used to our advantage on diborylated substrates. C—H activation/borylation coupled with deborylation has proved to be powerful method in synthesizing pinacol boronic esters, with regiochemistry complementary to the previously known methods and tolerant of a variety of functional groups. The mildness and stereospecificity of the reactions has allowed us to use deuteration and deborylation on advanced molecules like pharmaceuticals.N–Methyliminodiacetic acid protection has been used to attenuate the reactivity of the diboron compounds. It has allowed us to desymmetrize diboron compounds generated from Ir–catalyzed C—H activation/borylation and Miyaura borylation. The selective coupling of BPin leaving the BMIDA intact allows for the iterative cross–coupling. The utility of these substrates with two or more reaction sites in multi transformations has been demonstrated. This allows for the synthesis of complex organic molecules from simple building blocks.
Read
