Strategies to control the selectivity of transition metal catalyzed C-H functionalizations and a scalable synthesis of furan-2, 5-dicarboxylic acid by carbonate-promoted C-H carboxylation [electronic resource]

The selective activation and functionalization of C‒H bonds is an enduring challenge in chemistry with applications for both fine and commodity chemical synthesis. This thesis describes the investigation of two strategies to control selectivity in C--H functionalization reactions catalyzed by organometallic molecular catalysts and the development of a scalable C--H carboxylation method for commodity polymer synthesis. First, the use of externally applied electric fields to perturb the selectivity of a rhodium-catalyzed carbene insertion is investigated. The electrochemical double layer at an electrode--electrolyte interface is a region of high charge density with strong local electric fields. The Kanan lab previously observed selectivity changes for catalytic reactions confined to the double layer region, but these experiments were limited to analytical scales. To assess the scalability of this strategy and facilitate product analysis, reactors were designed and fabricated that enabled experiments on > 10-fold larger scales. These reactors were used to investigate interfacial field effects on the regioselectivity of a rhodium-catalyzed carbene insertion. The results revealed complex voltage- and electrolyte-dependent product distributions that illuminate several challenges for utilizing interfacial electric field effects. Second, ion pairing and ligand effects on the selectivity of Ru-catalyzed C‒H aminations is investigated. This study revealed that strongly donating ligands dramatically improved selectivity of the C--H insertion vs aziridination with di-ruthenium catalysts, leading to the development of a new catalyst, Ru2Espa2PF6. This catalyst is the most selective catalyst for specific allylic insertions, providing access to products that were previously inaccessible. Third, the use of alkali carbonate salts to promote the carboxylation of weakly acidic C--H bonds is investigated. Previous studies have shown that CO32-- can deprotonate diverse substrates including alkynyl, allylic, and activated heteroaryl C‒H bonds with pKa up to ~27 in organic solutions at elevated temperatures. Here it is demonstrated that CO32-- can deprotonate much less acidic C--H bonds, including phenyl and furanyl rings, when the reaction is performed in solvent-free alkali carboxylate salts. When performed under a CO2 atmosphere, the resulting carbanion reacts to form a carboxylate. Using this chemistry, the conversion of 2-furoate to furan-2,5-dicarboxylate is demonstrated. The diacid of this carboxylate, furan-2,5-dicarboxylic acid (FDCA), is a promising replacement for petroleum derived terephthalic acid in polyester synthesis. Since 2-furoic acid can be generated from furfural under mild oxidation conditions, and furfural is produced industrially from waste biomass, this chemistry presents as a possible way of synthesizing FDCA in a highly efficient and streamlined process from CO2, air, and waste biomass. The feasibility of scaling the CO32---promoted C--H carboxylation of 2-furoate was demonstrated by performing a mole-scale reaction in a packed-bed flow reactor with 89% isolated yield of pure FDCA.

Keywords: Chemistry.
Advisor: Kanan Matthew William
Du Bois Justin advisor. Thesis advisor
Waymouth Robert M. advisor. Thesis advisor