Borinic Acid-catalyzed Ring-opening of Epoxy Alcohols

Borinic acid catalysis has been used by our group to effect ring-opening and rearrangement reactions of 2,3-epoxy alcohols via reversible borinate ester formation. This work focuses on expanding the mode of borinic acid catalysis to the activation of 3,4-epoxy alcohols for regioselective ring-opening reactions with various nucleophiles. The current work is inspired by the methodology void for C3-selective ring-opening of homoallylic alcohol-derived epoxides, as literature precedence uses transition metal-based approaches that result in C4-selectivity. The prevalence of amino-, thiol-, and halodiol motifs in biologically important compounds, natural products, and synthetic intermediates for pharmaceutically pertinent molecules further encouraged research efforts in developing methodologies for the organoboron-catalyzed ring-opening reactions of epoxy alcohols.Chapter 1 discusses the development of a highly regioselective borinic acid-catalyzed methodology for ring-opening 3,4-epoxy alcohols with amines and thiols. A catalytic tethering mechanism that enables intramolecular delivery of the nucleophile to the epoxide is postulated to be responsible for the enhanced rate acceleration and regiocontrol observed. The resulting C3-ring-opening products from a broad substrate scope—including ones sterically biased to favour C4-selective outcomes—suggest the complementarity of this methodology to the current state-of-the-art C4-selective, transition metal-based protocols. Chapter 2 probes the mechanistic underpinnings of the catalytic cycle for the aminolysis of 3,4-epoxy alcohols. RPKA experiments using in situ reaction monitoring by NMR and ATR-IR spectroscopy are used to decipher the kinetic order dependences in catalyst and nucleophile. The derived rate law under catalyst inhibition by aniline agrees with results obtained using the VTNA method. Chapter 3 expands the borinic acid-catalyzed regioselective ring-opening methodology to halide nucleophiles, yielding C3-selective outcomes consistent with a boron-tethered mechanism. The regiocontrolled synthesis of halohydrin diols, from both 2,3- and 3,4-epoxy alcohols, presents a synthetically useful method for accessing these ubiquitous motifs in biologically relevant compounds. Chapter 4 discusses possible starting points for furthering the development of borinic acid catalysis relating to epoxy alcohol activation. Conducting more RPKA experiments can help elucidate the full catalytic cycle and shed insight on other promising nucleophiles that are compatible with the catalytic tethering mechanism exhibited by boron.

Department dc:contributor.department

Chemistry

Year dc:date.issued

2021

Author dc:creator

• Wang, Yu Fang Grace

Advisor dc:contributor.advisor

• Taylor, Mark S.

Statement dc:rights

• Attribution 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by/4.0/

Handle dc:identifier.uri

http://hdl.handle.net/1807/106394

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/106394