Intramolecular and Intermolecular Cyclizations of Benzyl Alkynyl Sulfones: Synthetic scope, Limitations and Mechanistic Studies

Ho, Uyen
Journal Title
Journal ISSN
Volume Title
University of Guelph

This thesis encompasses the investigation of two modes of base-induced cyclizations of benzyl alkynyl sulfones. Based on works previously published by the Schwan group, the key step of the cyclization was identified to be the formation of a benzylic anion, which undergoes cyclization by temporarily breaking aromaticity. Building on the proposed theory, substrates were developed to directly probe the key step. Unfortunately, no conclusive results were obtained. However, during the study, an unexpected compound, oxathiin-S,S-dioxide was isolated. These compounds possess a heterocyclic core and belong to a family of fungicides. This discovery inspired a novel systematic approach to substrates with multiple aryl substituents. Based on retrosynthetic analysis, substrates were treated with base, followed by a benzaldehyde to effect electrophilic capture and subsequent intramolecular conjugate addition to the triple bond. After thorough optimization, the reaction affords products with (het)aryl groups at the 5- and 6-positions in 23 – 78% yield.

sulfone, cyclization