Date of Graduation
Eberly College of Arts and Sciences
The synthesis of organoboron compounds is of contemporary importance in the chemistry community given their utility in subsequent functionalization reactions as well as their growing therapeutic potential in the treatment of human disease. This, coupled with the ubiquity of carboxylic acid functional groups in pharmaceuticals and fine chemicals, has led to interest in one-pot difunctionalization reactions using CO2 and a boron source. An (ICy)copper(I)-catalyzed boracarboxylation reaction was recently developed wherein CO2 and a pinacolboryl group is added across the double bond of vinyl arenes was recently developed, providing access to α-aryl-β-boryl propionic acid derivatives. A subsequent publication detailed the addition of PPh3 as a secondary ligand, which permitted boracarboxylation of previously inaccessible styrene derivatives while also reducing catalytic loading.
An extensive experimental and computational mechanistic study has been conducted to validate the proposed mechanism and to understand the electronic considerations and the additive effects on the system. More stable analogs to catalytically relevant complexes were synthesized using the bulkier IPr NHC ligand. The rates of carboxylation for IPrCuI(β-borylbenzylX) complexes with varying electronic properties were examined, and results indicated the strong preference for electron rich vinyl arene substrates originates in the carboxylation step of the mechanism. PPh3 and exogenous alkene additives enhanced the rates of carboxylation for severely electron deficient IPrCuI(β-borylbenzylCF3), suggesting alternative pathways for CO2 incorporation are operative.
Complementary computational studies were performed using density functional theory (DFT) to explore the effects of electronics of the vinyl arene and the inclusion of additives for carboxylation. Further, the effect of the Lewis acidity of the boron moiety on CO2 insertion was evaluated using boron valence deficiency. Analyses of these data corroborate conclusions drawn about an alternative mechanism determined experimentally and provided evidence of a Lewis acid/base cooperative interaction between the boron center and CO2 that promotes carboxylation.
Baughman, Notashia Nicole, "Mechanistic Analysis of Reductive Boracarboxylation Using Low Valent Copper and CO2" (2020). Graduate Theses, Dissertations, and Problem Reports. 7940.