Direct functionalization of C⁰́₂H bonds reduces the number of synthetic steps for a target molecule enhancing efficiency and avoiding undesired waste material. Iridium catalyzed C-H activation-borylation (CHB) is an established method to access aryl boronic esters. Regioselectivity challenges can arise when multiple hydrogens are present in the molecule. This thesis describes the design of novel strategies to selective direct the CHB to one specific position.Ortho selective CHB has the challenge to go against the traditional CHB selectivity dictated by steric effects. Previously, our group reported a strategy for highly ortho-selective CHB of anilines by using a small B2eg2 (eg = ethanediol) as the borylating reagent. However, the products were unstable and transesterification with pinacol was needed. Chapter 2 builds upon this issue and presents a solution based on the modulation of the size of the boron partner. Small diboron partners retain the high ortho regioselectivity for CHB of aniline but larger borylating reagents generate more stable products. In our estimation, B2bg2 (bg = 1,2-butanediol) represents the best balance of reactivity, regioselectivity and stability.Remote functionalization including para selective reactions are difficult because a potential directing group would be far from the desired reactive site. Chapter 3 details how para CHB of tetraalkylammonium sulfates and sulfamates have been achieved using bipyridine-ligated Ir boryl catalysts. Selectivities can be modulated by both the length of the alkyl groups in the tetraalkylammonium cations and the substituents on the bipyridine ligands. Ion pairing, where the alkyl groups of the cation shield the meta C⁸́₂H bonds in the counteranions, is proposed to account for para selectivity. The 4,4'-dimethoxy-2,2'-bipyridine ligand gave superior selectivities.The next chapter describes how intramolecular hydrogen bonding (IMHB) can lead to steric shielding effects that can direct CHB regiochemistry. Bpin/arene IMHB can promote remote borylations of N-borylated anilines, 2-amino-N-alkylpyridine, tetrahydroquinolines, indoles and 1-borylated naphthalenes. Our studies support molecular geometries with the Bpin orientation controlled by a C-H⁰́Ø⁰́Ø⁰́ØO IMHB. Calculated rotation barriers to displace the Bpin group are above 4 kcal/mol, suggesting that the planar ground conformation of the borylated arenes is retained during CHB. This study informs researchers to evaluate not only inter- but also intramolecular noncovalent interactions as potential drivers of remote CHB regioselectivity.The borylated products from CHB can be further manipulated in Suzuki-Miyaura cross-coupling (SMC) with aryl halides as the typical electrophilic partner. Aryl imidazolylsulfonates are nongenotoxic electrophiles that can be used in palladium catalyzed SMC to avoid halogenated materials. Chapter 5 shows the efforts towards a nickel-catalyzed SMC of aryl imidazolyl-sulfonates. Results show considerable amounts of the corresponding diarylsulfate formed during the reaction. Interestingly, the diaryl sulfa byproducts were found to be competent electrophilic partners for both palladium and nickel-catalyzed SMC.In summary, this thesis presents novel methodologies to access challenging transformations as the para borylations of phenols, anilines and benzyl alcohols. This was possible by the analysis of the different components of the catalytic system: design of ligands, diboron partners and substrate directing groups and how they interact during the reaction. Finally, the potential of aryl imidazolylsulfonates as nongenotoxic pseudohalides in nickel-catalyzed SMC was evaluated.
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