Dissertation
Pyridine activation: strategies for carbon-carbon bond formation on heterocyclic scaffolds
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2022
DOI: 10.25820/etd.006723
Abstract
Aza heterocycles are ubiquitous structures in active pharmaceutical ingredients, natural products, and materials chemistry. Despite their importance, major synthetic challenges persist when manipulating such compounds. The objective of the work contained in this thesis was to develop new carbon-carbon bond forming reactions on aza heterocylic scaffolds. Specifically, development of new strategies to achieve pyridine activation resulted in three new types of transformations suitable for functionalizing simple pyridine substrates.An improved preparation of N-alkenyl-2-pyridones was achieved starting from 2-halopyridinium salts. This transformation circumvents the issue of mixed N- and O- alkylation encountered in established pyridone reactions and allows for milder reaction conditions than other reported manipulations of pyridone ring systems. Several different aldehydes and 2-halopyridine derivatives successfully gave the reaction, and the N-alkenyl pyridone products are amenable to further elaboration as demonstrated in several examples.
Moreover, 4-alkenyl pyridines were prepared through a homologation sequence between activated 4-alkyl pyridines and an electrophilic methylene source. These exceedingly simple and mild reaction conditions enable a unique alkenylation strategy that minimizes functional group demands required for alternative preparations of geminally disubstituted alkenyl pyridines.
Furthermore, allylated 4- and 2-alkyl pyridines were successfully prepared from N-allyl pyridinium salts in the presence of palladium catalysts. This reaction demonstrated efficacy for both 2- and 4-alkyl pyridines, and important reaction parameters influencing the success of this allylation strategy were identified.
Details
- Title: Subtitle
- Pyridine activation: strategies for carbon-carbon bond formation on heterocyclic scaffolds
- Creators
- Grant N. Shivers
- Contributors
- F. Christopher Pigge (Advisor)Edward G. Gillan (Committee Member)David Martin (Committee Member)Elizabeth A. Stone (Committee Member)David F. Wiemer (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Chemistry
- Date degree season
- Summer 2022
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.006723
- Number of pages
- xiii, 389 pages
- Copyright
- Copyright 2022 Grant N. Shivers
- Comment
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- Language
- English
- Description illustrations
- Illustrations, charts, graphs, tables
- Description bibliographic
- Includes bibliographical references (pages 368-389).
- Public Abstract (ETD)
Nitrogen containing ring systems are common in pharmaceuticals, natural products, and materials chemistry. Accordingly, methods to prepare and manipulate these rings systems are of high value. However, many traditional reaction strategies are incompatible with these ring systems, and reactions that address the issues governing these molecules remain underdeveloped. The primary goal of this work is to address some of these problems by activating the nitrogen in these molecules, facilitating further carbon-carbon bond forming transformations. New reactions towards the synthesis of N-alkenyl-2-pyridones, 4-alkenyl pyridines, and allyl substituted 2- and 4-alkyl pyridines have been developed and are the topic of this thesis.
- Academic Unit
- Chemistry
- Record Identifier
- 9984285452702771
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