Mechanistic Analysis of Reductive Boracarboxylation Using Low Valent Copper and CO2

Author

Notashia Nicole Baughman, West Virginia UniversityFollow

Semester

Fall

Date of Graduation

2020

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Chemistry

Committee Chair

Brian Popp

Committee Member

Carsten Milsmann

Committee Member

Jessica Hoover

Committee Member

Brian Dolinar

Committee Member

Werner Geldenhuys

Abstract

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 IPrCu^I(β-borylbenzyl^X) 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 IPrCu^I(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.

Recommended Citation

Baughman, Notashia Nicole, "Mechanistic Analysis of Reductive Boracarboxylation Using Low Valent Copper and CO2" (2020). Graduate Theses, Dissertations, and Problem Reports. 7940.
https://researchrepository.wvu.edu/etd/7940