The studies in this dissertation are aimed at uncovering reactive and selective Ir-catalyzed C-H borylation (CHB) catalysts. Due to the high versatility of organoboron species, green methodology to produce the C-B bond is poised to support a myriad of subsequent transformations. These transformations include Suzuki couplings, aminations, oxidations, halogenations, cyanations, and trifluoromethylations.Typical iridium catalyzed CHBs proceed through an iridium trisboryl with a bidentate ligand such as bipyridine or 1,10-phenanthroline. The selectivity of these standard catalysts is generally driven by sterics; however, many methods of overcoming the steric bias have been developed in the two decades since the first thermal catalytic C-H activation borylation. These methods include both inner- and outer-sphere directed mechanisms. Outer-sphere directed borylations have been accomplished by leveraging hydrogen bonding, Lewis acid-base, and ion-pairing as directing elements. In general this reactivity is activated by precise design of the bidentate ligand framework.Herein is reported a subtle electrostatic interaction to direct ortho-borylation of phenols by simply switching boron source from the common B2pin2 (pin = pinacolate) to B2eg2 (eg = ethyleneglycolate). This electrostatic interaction was revealed by a careful computational analysis of key C-H activation transition states. Understanding gained by the computational studies led to the redesign of the boron source which enabled by selectivities of > 99% ortho borylation. This methodology was extended to the highly selective ortho-borylation of anilines, and the underlying mechanism has been interrogated.Currently, iridium based catalysts have been generated to borylate ortho, meta, and even para to a variety of classes of substrates; however, control of selectivity can breakdown in many fluorinated arenes without a directing group. These substrates are challenging because the fluoro moiety being similar in size to a hydrogen offers little in the way of steric bias. While working to overcome these challenges, a serendipitously discovered hydrazone based ligand was discovered. Exploration of the catalysts generated by this ligand revealed not only impressive activity rivaling dtbpy but also incredible selectivity for meta to a fluoro group.In general iridium CHB catalysts selectively activate sp2 C-H bonds leaving all sp3 C-H bonds intact; however, a method to turn on sp3 C-H activation would be desirable. It was reasoned that a directing group able to increase the effective concentration of the iridium catalyst near a C(sp3)-H bond may enable this transformation. Indeed, it was discovered that catalysts able to accept amide directing groups were able to selectively borylate compounds with amide N-methyl substituents.
Read
