Advances in Iridium-Catalyzed C-H Borylation Enabled by 2,2’-Dipyridylarylmethane Ligands
Jones, Maggie Rose
Direct functionalization of unactivated C-H bonds presents a longstanding challenge in the field of synthetic chemistry, largely addressed by the use of low-valent transition metal catalysts and development of corresponding ligand platforms. Particularly, the field of catalytic C–H borylation has grown considerably since its founding, providing a means for the preparation of synthetically versatile organoborane products. The contents of this dissertation detail the design and examination of 2,2’-dipyridylarylmethane ligands envisioned to remedy current limitations to iridium-catalyzed sp2 and sp3 C-H borylation. Sp2 C–H borylation methods have found widespread and practical use in organic synthesis, however, regioselective transformations of monosubstituted arenes remain limited to a select few examples. Catalyst-induced selectivity is investigated, aimed at controlling site of functionalization through 2,2’-dipyridylarylmethane ligand features or secondary recognition elements. The analogous sp3 C–H borylation reaction remains challenging and has seen limited application to unactivated substrates; Existing catalysts are often hindered by incomplete consumption of the diboron reagent, poor functional-group tolerance, harsh reaction conditions, and the need for excess or neat substrate. The 2,2’-dipyridyl(3-fluorophenyl)methane ligand was identified to give highly active alkane borylation catalysts that facilitate C−H borylation with improved efficiency. This system provides for complete consumption of the diboron reagent, producing two molar equivalents of product at low catalyst loadings. The superior efficacy of this system also enables borylation of unactivated alkanes in hydrocarbon solvent with a reduced excess of substrate and improved functional group compatibility. Examination of structural and mechanistic features of this highly effective catalyst is also conducted, providing evidence in support of the envisioned facial κ3 coordination mode as an active catalyst species. Subtle manipulations of ligand structure are also demonstrated to have a profound impact on activity and speciation of the resulting catalyst, exemplifying the value of ligand development in the advancement of catalyst platforms.