Chemistry, Department of
First Advisor
Dr. James M. Takacs
Date of this Version
Summer 7-31-2019
Document Type
Article
Citation
Chakrabarty, Suman. Phosphonate-Directed Catalytic Asymmetric Hydroboration: Synthesis of Functionalized Chiral Secondary and Tertiary Boronic Esters and Mechanistic Insights. 2019 University of Nebraska-Lincoln. PhD Dissertation.
Abstract
Over the past 30 years, catalytic asymmetric hydroboration (CAHB) of alkenes has emerged as a leading methodology to access chiral primary and secondary boronic esters. However, it wasn’t until 2015 that directed-CAHB was for the first time shown to efficiently access chiral tertiary boronic esters. The latter are excellent precursors to synthetically challenging structural motifs such as chiral tertiary alcohols, carbinamines and all-carbon quaternary stereocenters via stereospecific C-B bond substitutions. This dissertation focuses on phosphonate-directed CAHB of diverse alkene substrates, including challenging stereodefined trisubstituted alkenes, to efficiently access multifunctional chiral secondary and tertiary boronic esters. Mechanistic insights obtained via deuterium labelling experiments indicate that CAHB reactions proceed via tertiary-alkyl rhodium intermediates for substrates that lead to chiral tertiary boronic esters. The applications of phosphonate-functionalized chiral secondary and tertiary boronic ester products are discussed in the context of stereospecific C-B bond transformations, through phosphonate unmasking methodologies via thiophosphonate and oxophosphonate intermediates, and through synthesis of the cytotoxic natural product bakuchiol.
Advisor: James M. Takacs
Comments
A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Chemistry, Under the Supervision of Professor James M. Takacs. Lincoln, Nebraska, United States: July 2019
COPYRIGHT DISCLAIMER
Parts of the research work compiled in this dissertation are published separately in three different academic research journals which are listed below:
(1). Chakrabarty, S.; Palencia, H.; Morton, M. D.; Carr, R. O.; Takacs, J. M. "Facile access to functionalized chiral secondary benzylic boronic esters via catalytic asymmetric hydroboration", Chem. Sci., 2019, 10, 4854-4861. DOI: 10.1039/C8SC05613G. Copyright © The Royal Society of Chemistry 2019
(2). Chakrabarty, S.; Takacs, J. M. "Phosphonate-Directed Catalytic Asymmetric Hydroboration: Delivery of Boron to the More Substituted Carbon, Leading to Chiral Tertiary Benzylic Boronic Esters", ACS Catal., 2018, 8, 10530-10536. DOI: 10.1021/acscatal.8b03591. Copyright © 2018 American Chemical Society
(3). Chakrabarty, S.; Takacs, J. M. "Synthesis of Chiral Tertiary Boronic Esters: Phosphonate-Directed Catalytic Asymmetric Hydroboration of Trisubstituted Alkenes", J. Am. Chem. Soc., 2017, 139, 6066-6039. DOI: 10.1021/jacs.7b02324. Copyright © 2017 American Chemical Society
NOTICE TO THE READER: Copyright permission was obtained from each of the three journals cited above for reproduction of the entire content of each manuscript in this dissertation. The publication sources are cited for each reproduction of the original content (text/figures) made in this dissertation. For further permissions related to the material(s) excerpted, the reader should direct further permissions to the respective journal in which the work is published. Copyright for this dissertation is reserved by the author.