| Biaryls are important targets for numerous applications in organic synthesis. As a result, the development of metal-mediated aryl cross-coupling has been extensively studied. The disadvantage of this approach is the requirement for each coupling partner to be prefunctionalized. To address this challenge, our studies focused on the development of direct, site selective C--H arylation.;We developed a PdII-catalyzed, ligand-directed C--H arylation reaction, that employs [Ar--IIII--Ar] + reagents as terminal oxidants. High site-selectivity was achieved by employing substrates containing either oxygen or nitrogen-directing groups for functionalization of a specific C--H bond. This approach led to the installation of both electron rich and electron poor aryl groups. Additionally, excellent functional group tolerance was observed. Finally, investigations found that the generation of [Ar---IIII---Ar] + in situ were feasible for subsequent C--H functionalization.;Mechanistic investigations of directed C--H arylation elucidated the catalytic cycle. This represents the first thorough investigation of a ligand-directed, palladium- catalyzed C--H arylation. These studies implicated a high-oxidation state dimeric palladium species as a catalytic intermediate. Furthermore, oxidation was found to be rate-limiting, unlike most C--H functionalization reactions.;We also extended this methodology to the C--H arylation of substrates lacking a directing group. We demonstrated that palladium catalysts and [Ar--I III--Ar]+ oxidants afford site selective C2 arylation of indoles at room temperature, with excellent functional group tolerance. The installation of both electron rich and electron poor indoles, with electronically diverse of aryl groups was achieved. The viability of in situ oxidant generation, followed by indole arylation also was shown. Preliminary mechanistic investigations of indole arylation implicated the formation of an active catalyst prior to arylation.;This dissertation describes the development of site selective C--H arylation reactions using palladium catalysis. These transformations are general with respect to aryl group and substrate, and are complimentary to Pd 0/II catalytic cycles. The functional group tolerance, broad substrate scope, and variety of installed aryl groups, make this methodology attractive for biaryl synthesis. |
