Design and Mechanistic Understanding of New Boronic Acid Catalyst Systems

• Author / Creator

  Rygus, Jason P. G.

• Catalysis is essential to the modern chemical industry. Catalytic strategies can enable new synthetic methods with improved atom economy and reduced chemical waste under mild conditions, representing an indispensable approach to the development of green chemical processes with improved sustainability. New advances in catalysis can facilitate the discovery of new bond-forming reactions using ubiquitous starting materials for which direct activation has otherwise proven challenging. In this context, boronic acid catalysis has emerged as a promising strategy for the direct activation of hydroxy-containing functional groups under mild conditions, allowing for conversion of these common motifs into functionalized products without the need for wasteful pre-activation steps. In this thesis, advances towards the development and understanding of new catalytic systems in boronic acid catalysis are presented.

  The modification of catalyst activity in situ using suitable additives has rarely been explored as a reactivity-enabling strategy in boronic acid catalysis. In Chapter 2, the use of perfluoropinacol as a co-catalyst in the boronic acid-catalyzed Friedel-Crafts benzylation of electron-deficient benzylic alcohols for the synthesis of triarylmethanes is described. Mechanistic studies reveal that condensation of perfluoropinacol with the boronic acid catalyst leads to generation of a hydronium boronate species, which is likely responsible for C–O activation through indirect Brønsted acid catalysis.

  Although boron-containing heterocycles have found wide ranging application in drug discovery and materials science, their application in catalysis has been hindered by a poor understanding of their inherent acidity, stability, and reactivity. Chapter 3 of this thesis details a systematic study on a series of model pseudoaromatic benzoxazaborine and benzodiazaborine heterocycles. While all compounds are unambiguously demonstrated to act as Lewis acids, their acidity and boranol (B–OH) exchangeability with exogenous alcohols is highly dependent on the nature of the endocyclic heteroatom. Dynamic crossover experiments reveal that N-sulfonyl substituted benzodiazaborines are unstable towards ring-opening in methanol, while computational studies suggested that the boron-containing rings retain little aromaticity of their all-carbon analogs.

  Chapter 4 presents the rational application of the benzoxazaborine scaffold in two mechanistically divergent modes of boronic acid catalysis. The parent heterocycle is found to be an effective catalyst for the nucleophilic activation of vicinal diols towards monophosphorylation, while a cationic hemiboronic acid is found to be highly active for the electrophilic activation of alcohols and ketones towards reductive deoxygenation in the presence of a silane. Mechanistic investigations of both transformations reveal the contrasting nature of crucial tetravalent boron species in the two catalytic manifolds and demonstrated that mechanistically guided structure-activity relationships can be employed in the design of new hemiboronic acid catalysts.

• Subjects / Keywords

  • chemistry
  • organic chemistry
  • catalysis
  • boron

• Graduation date

  Spring 2023

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-7tta-nz63

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.