Since its discovery in 1999, Ir-catalyzed C-H activation/borylation has established itself as a potent tool for the construction of aromatic and heteroaromatic building blocks. Given their bench stability and versatility in chemical transformations, the use of boronates is synthetically advantageous. Catalysis by iridium features a regioselectiviy that is primarily directed by sterics, as opposed to electronics, complementing electrophilic aromatic substitution and functional group-directed metalation. Synthetic utilization of this characteristic allows access to structural moieties that are, in fact, relatively inaccessible via traditional routes. This last decade has been prolific with work on improvements, adaptations, and various applications of such borylations reported by many research groups.Herein, a number of synthetic aspects of this chemistry are discussed. Halogen tolerance, for instance, allows for the preparation of multifunctional cross-coupling partners as useful building blocks. This feature is showcased in the diversity-oriented route to the COX-2 inhibitor DuP 697 and a series of analogs. The special regioselectivity attained on heteroaromatics has been utilized toward the development of a novel convergent route to the TMC-95 core. For this purpose, preparation of a key intermediate was made possible via a neutral and mild Ir-catalyzed deborylation method, developed in our laboratories, that allows the preparation of heteroaromatics with unusually placed boronate groups via diborylation/monodeborylation. In addition, the same gentle deborylation procedure was adapted for the preparation of deuterium-labeled compounds in a site-selective manner, emphasizing the importance of the broad functional group tolerance of Ir-catalyzed C-H activation/borylation.Perhaps the most attractive of its characteristics is that, given the cleanliness with which it proceeds, Ir-catalyzed C-H activation/borylation is amenable to one-pot transformations. This concept is highlighted in our synthetic approach to the Hsp90 inhibitor autolytimycin. Taking advantage of both the regioselectivity and halogen tolerance, our method enabled a highly convergent construction of the full carbon network of this natural product. We provide an illustration of a C-H activation/borylation-based three-step one-pot process, which is complemented by a B-alkyl sp3-sp2 Suzuki coupling on a highly inactivated aromatic chloride, an unprecedented transformation in complex molecule synthesis. The late-stage applicability of these boron-based methods lead to the preparation of highly elaborated 5-alkyl-3-amidophenols, motifs that are present in many natural products and that are difficult to obtain via conventional methods.
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