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

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Hilby, Kimberly Muno

Contributors dc:contributor

• Denmark, Scott E
• Hergenrother, Paul
• Chan, Jefferson
• Sarlah, David

• Chemistry

Statement dc:rights

• Copyright 2021 Kimberly Hilby

Language dc:language

en, eng

Handle dc:identifier

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

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F113823