University of Illinois Urbana-Champaign

The development of dearomative functionalizations and their use in the total synthesis of bioactive natural products

Bingham, Tanner William

This item's files can only be accessed by the System Administrators group.

Permalink

https://hdl.handle.net/2142/115652

Description

Title
The development of dearomative functionalizations and their use in the total synthesis of bioactive natural products
Author(s)
Bingham, Tanner William
Issue Date
2022-01-27
Director of Research (if dissertation) or Advisor (if thesis)
Sarlah, David
Doctoral Committee Chair(s)
Sarlah, David
Committee Member(s)
  • Denmark, Scott E
  • Hergenrother, Paul J
  • White, Christina M
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
  • Total Synthesis
  • Scalability
  • Dearomatization
  • Aromatic Compounds
  • MTAD
  • Amaryllidaceae Isocarbostyril Alkaloids
Abstract
The dearomatization of aromatic compounds, some of the most abundant feedstock chemicals, has been heavily studied over the past century. Despite their widespread use, most methods for dearomatization do not result in the introduction of additional functionality. This dissertation describes the use of N-methyl-1,2,4-triazoline-3,5-dione (MTAD) in the development of various dearomative functionalization reactions as well as its use in the total synthesis of bioactive natural products. A total synthesis of the highly potent anticancer natural products, the Amaryllidaceae isocarbostyril alkaloids, was developed. The brevity and scalability of our synthesis was due to the development of a nickel-catalyzed asymmetric dearomative carboamination reaction, providing a stereodefined diene that provided facile access to the cyclitol core of these natural products. The utility of this dearomative functionalization reaction led us to explore similar types of reactivity, ultimately leading to the development of dearomative cyclopropanation, a dearomative Pauson-Khand reaction, and three different dearomative allylic substitution reactions — 1,4-hydroamination, trans-1,4- carboamination, and syn-1,2-diamination. We also explored the dearomative functionalization of heteroarenes and found that substituted pyridines were viable substrates. Dearomative dihydroxylation, diimide reduction, and epoxidation were all able to provide dearomatized products in synthetically useful yields. Further elaboration of these substrates was able to provide rapid access to substituted piperidines and piperidones.
Graduation Semester
2022-05
Type of Resource
Thesis
Copyright and License Information
Copyright 2022 Tanner Bingham

Owning Collections

Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois