Development of a Lewis base catalyzed, sulfenium-ion initiated enantioselective, spiroketalization cascade

Hilby, Kimberly Muno

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https://hdl.handle.net/2142/113823 Copy

Description

Title

Development of a Lewis base catalyzed, sulfenium-ion initiated enantioselective, spiroketalization cascade

Author(s)

Hilby, Kimberly Muno

Issue Date

2021-10-26

Director of Research (if dissertation) or Advisor (if thesis)

Denmark, Scott E

Doctoral Committee Chair(s)

Denmark, Scott E

Committee Member(s)

• Hergenrother, Paul
• Chan, Jefferson
• Sarlah, David

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Organic synthesis
• Spiroketals
• Methodology development

Abstract

This thesis covers the development of a Lewis base-catalyzed, enantioselective sulfenocyclization of olefins to afford [6,6]-spiroketals. Starting with an introduction on Lewis base catalysis and the prior work done in asymmetric spiroketalization cyclizations (Chapter 1), the thesis will then focus on the development of different synthetic routes towards the different substrate classes that were explored in the reaction: 1) alkyl-tethered alcohols, 2) phenol tethered alcohols and finally 3) benzyl-tethered alcohols (Chapter 2). Finally, the optimization and exploration of a sulfenion-ion initiated spiroketalization reaction (Chapter 3). The method uses a chiral Lewis base catalyst with an electrophilic sulfur source to generate enantioenriched thiiranium ion with alkenes. Upon formation, the thiiranium ion is subsequently captured in a cascade-type reaction, wherein a ketone oxygen serves as the nucleophile to open the thiiranium ion and an alcohol provides the secondary cyclization to form biorelevant spiroketals. A variety of electron-rich and electron-neutral E-substituted styrenes form the desired spiroketals in good yields with excellent enantio- and diastereoselectivities. Alkyl-substituted and terminal olefins participate in the cascade reaction, but with a limited scope compared to the styrenyl substrates. Benzofused substrates were found to be competent and provide a variety of different substituted benzofused spiroketals in good yields, enantioseletivities and diastereoselectivities. Finally, the future directions of this project are explored: 1) further mechanistic studies to elucidate the mechanism of the reactions using computational chemistry 2) the application to the total synthesis of benzofused [6,6]-spiroketals and 3) the application towards the synthesis of [5,5] and [5,6] spiroketals.

Graduation Semester

2021-12

Type of Resource

Thesis

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http://hdl.handle.net/2142/113823

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Copyright 2021 Kimberly Hilby

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