Sequential Enantioselective Iridium-Catalyzed Allylic Alkylation/Cope Rearrangement for the Construction of Acyclic γ-Tertiary or Quaternary Stereocenters

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.

Department dc:contributor.department

Chemistry

Year dc:date.issued

2024

Author dc:creator

• Xie, Hengmu

Advisor dc:contributor.supervisor

• Evans, P. Andrew

• Allylic alkylation
• Cope rearrangement

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1974/34222

OAI identifier oai:identifier

oai:queensu.scholaris.ca:1974/34222