Breaking New Ground with the Suzuki-Miyaura Reaction: Stereoselective Cross-Couplings of 1,1-Diboronyl Alkanes

• Author / Creator

  Sun, Ho-Yan

• Synthetic organic chemistry is an area that has seen incredible growth through the years. The level of molecular complexity that can be achieved through available synthetic methods today is remarkable. Still, as the field continues to progress, increasing focus is being placed upon the strategic development of methods that are both efficient and selective in order to allow for the rapid assembly of molecular complexity. In this regard, organoboron reagents represent a class of compounds that have demonstrated great synthetic diversity. These compounds have been applied, through a range of methods, in the efficient construction of C-heteroatom and C-C bonds. Arguably among some of the most frequently used processes is the Suzuki-Miyaura cross-coupling. Since its conception, this reaction has been widely applied in a broad range of fields including, but not limited to, the pharmaceutical and materials industries. To date, the application of the Suzuki-Miyaura cross-coupling to the construction of sp2-sp2 bond connections has been extensively studied and many groups are now directing efforts towards employing this method for the construction of stereogenic centres. To this end, this thesis details studies in developing catalytic stereoselective Suzuki-Miyaura reactions for the cross-coupling of sp3-hybridized organoboronates for the efficient construction of stereogenic carbon centres.
  In order to demonstrate the versatility of optically enriched diboronyl compounds, Chapter 2 describes the development of an iterative cross-coupling process to transform 3,3-diboronylamides into the corresponding diarylmethanes – a motif that is commonly found in pharmaceutically relevant compounds. In addition, studies were made to determine the stereochemical outcome of the cross-coupling reaction.
  As a progression from the cross-coupling of optically enriched secondary boronates, Chapter 3 describes the development of an asymmetric Suzuki-Miyaura cross-coupling reaction for the desymmetrization of prochiral 1,1-diboronylalkanes. Ligand optimization in combination with mechanistic studies on the role of the base led to reaction conditions that produced optically enriched secondary organoboronates in good yields and enantioselectively. The details of the reaction scope and scalability will also be discussed.
  Due to the synthetic value demonstrated by 1,1-diboronyl compounds, an extension of these cross-coupling methods to 1,1,1-triboronylated compounds is desirable, as this would represent a unique way to construct complex stereogenic centres. In Chapter 4, initial studies on the synthesis of 1,1,1-triboronyl alkanes will be described. Given their similar potential as a synthetic handle for the construction of stereogenic centres, the development of a method that produces 3,3-diboronyl 3-silyl ketones as the products will also be discussed.

• Subjects / Keywords

  • Catalysis
  • Palladium
  • Suzuki-Miyaura
  • Stereoselective couplings
  • Organoboronates

• Graduation date

  Fall 2015

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3W669H2P

• 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.