Boronic Acid Catalysis: A Versatile Strategy for Direct Hydroxyl Group Functionalization

  • Author / Creator
    Mo, Xiaobin
  • The field of organic chemistry has seen remarkable advances throughout the decades. Of all advances, catalysis is playing a crucial role, since it can lower the activation energy of normally inert starting materials for further chemical reactions. In this context, the catalytic direct activation and transformation of hydroxyl groups (–OH) is of significant value since hydroxyl groups exist in numerous commodity chemicals, pharmaceutical agents and natural products. Arylboronic acids can form covalent bonds with hydroxyl groups in a reversible manner, thus providing transient activation, which bypasses the need for wasteful, expensive and often toxic stoichiometric activating reagents. As an emerging mode of catalysis, boronic acid catalysis (BAC) has the potential to be developed into a versatile strategy for direct hydroxyl group functionalization. To this end, BAC has been applied to the direct activation of carboxylic acids, alcohols and oximes. Several new catalytic methods employing novel arylboronic acids are presented in this thesis. Chapter 2 describes the development of a direct Friedel-Craft alkylation using π-activated alcohols via BAC. Owing to their high Lewis acidity, electron deficient arylboronic acids activate alcohol substrates though polarization of the C–O bond. Mechanistic investigation revealed that the catalytic reactivity of arylboronic acids is influenced by their ortho-substituents. Moreover, this chapter also details the discovery of a novel cationic ferrocenium boronic acid salt for the efficient Friedel-Crafts benzylation of challenging substrates. Due to its broad functional group tolerance, BAC can potentially be employed cooperatively with other types of catalytic systems. Chapter 3 describes the development of a dual catalytic methodology, merging boronic acids and chiral amines, for the direct asymmetric allylation of branched aldehydes with allylic alcohols. Through the optimization of boronic acids and various chiral amines, compounds containing valuable all-carbon quaternary centers can be accessed in good yield and high enantioselectivity. This research was also applied in the first catalytic and asymmetric synthesis of a key building block for the synthesis of a NK1/NK3 receptor antagonist. Other functional groups containing hydroxyl units may also be amenable to BAC. Chapter 4 describes the discovery of a unique class of arylboronic acids with ortho-carboxyesters for catalysis of the Beckmann rearrangement of oximes. A broad substrate scope of oximes with various functional groups is achieved. Further investigations strongly suggest a two-step mechanism comprised of a novel boron induced oxime transesterification and a boron assisted Beckmann rearrangement.

  • Subjects / Keywords
  • Graduation date
    Fall 2017
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • 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.