Transformations of cyclopropanols via zinc homoenolate and enolized homoenolate

• Main Author: Yoshiya, Sekiguchi
• Other Authors: Chiba Shunsuke
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2023
• Subjects: Science::Chemistry::Organic chemistry::Organic synthesis
• Online Access: https://hdl.handle.net/10356/164550
• Institution: Nanyang Technological University

Cyclopropanols have emerged as easily accessible precursors for the in situ generation of keto-homoenolates in the presence of metal catalysts and reagents. This thesis describes the discovery and development of three different transformations of a cyclopropanol that utilize a zinc homoenolate as a common intermediate. Chapter 1 provides a general introduction to the chemistry of metal homoenolate and its enolized species referred to as enolized homoenolate, followed by the design and summary of this thesis research. Chapter 2 describes the development of a zinc-catalyzed enantioselective ring-opening conjugate addition of a cyclopropanol to an enone. A catalyst generated from diethylzinc and a chiral β-aminoalcohol promotes ring-opening/1,4-addition of the cyclopropanol to the enone to give a 1,6-diketone, which then undergoes intramolecular aldol condensation to afford a cyclopentene derivatives in good yield and enantioselectivity. Chapter 3 describes a zinc-catalyzed β-allylation of a cyclopropanol with a Morita−Baylis−Hillman (MBH)-type allylic carbonate with retention of the cyclopropane ring. The key intermediate in this reaction is a catalytically generated enolized homoenolate, which is a bis-nucleophilic species generated through enolization of a zinc homoenolate intermediate. The enolized homoenolate reacts with the MBH carbonate at the α-position to generate the β-allylated zinc homoenolate, which then undergoes cyclization to afford the β-allylated cyclopropanol. Chapter 4 describes a zinc-mediated α-hydroxyallylation of an aldehyde with a cyclopropanol via an enolized homoenolate. In this reaction, the enolized homoenolate acts as a γ-oxyallyl nucleophile and reacts with the aldehyde to form a vicinal anti-sec,tert-diol in a diastereoselective manner.