Sequential Enantioselective Iridium-Catalyzed Allylic Alkylation/Cope Rearrangement for the Construction of Acyclic γ-Tertiary or Quaternary Stereocenters
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Authors
Xie, Hengmu
Date
2024-12-16
Type
thesis
Language
eng
Keyword
Allylic alkylation , Cope rearrangement
Alternative Title
Abstract
Functionalized carbonyl compounds with extended chiral carbon chains are commonly found in natural and synthetic bioactive molecules. However, catalytic asymmetric γ-functionalization of carbonyl derivates is challenging because of the issues with ontrolling chemo- (O vs. C), regio- (α vs. γ), and enantioselectivity. In this way, enantioselective transition metal-catalyzed γ-allylic alkylation reactions have attracted increasing attention, albeit they are typically restricted to cyclic nucleophiles. A direct strategy to construct acyclic γ-allylated carbonyl derivates is underdeveloped due to the challenging regio- and enantiocontrol, especially for constructing quaternary stereocenters. In this regard, an innovative strategy that sequential enantioselective iridium-catalyzed allylic alkylation/Cope rearrangement to provide an efficient method approach to acyclic γ-tertiary and quaternary stereocenters. The following thesis is divided into four chapters, which encompass a comprehensive literature review followed by two research chapters, further divided based on the type of transformation discussed.
Chapter 1 commences with a brief introduction to the enantioselective catalytic γ-functionalization of carbonyl derivates, which is followed by a comprehensive review divided into two major subsections based on the type of pronucleophiles, namely homoenolate and dienolate equivalents, which are further subdivided into cyclic and acyclic nucleophiles.
Chapter 2 highlights the development of enantioselective iridium-catalyzed γ-allylic alkylation of acyclic pronucleophiles. This chapter begins with a review of the iridium-catalyzed allylic substitution reactions, which includes seminal examples. While direct enantioselective iridiumγcatalyzed allylic alkylation at γ-position remains a significant challenge. Hence, we developed an indirect enantioselective iridium-catalyzed γ-allylic alkylation with a broad range of acyclic α,β-iii unsaturated cyanoacetates, and allylic carbonates, which can efficiently construct acyclic γ-tertiary stereocenters at mild conditions. Chapter 3 illustrates the development of a sequential enantioselective iridium-catalyzed allylic alkylation/Cope rearrangement for the construction of acyclic γ-quaternary stereocenters. This chapter opens with a review of the historical development of the construction of acyclic quaternary stereocenters, which are limited to adjacent positions of carbonyl groups. Then, our approach involves iridium-catalyzed γ-allylic alkylation of a series of acyclic disubstituted α,β-unsaturated malononitrile for the construction of quaternary stereocenters via a sequential α-allylic alkylation and in situ Cope rearrangement. Chapter 4 highlights some future works.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivatives 4.0 International