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

Bingham, Tanner William

Permalink

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

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