Studies of Oxidopyrylium Ylide Dimers and Their Utility in the Synthesis of Densely Functionalized Troponoids

Author

Daniel V. Schiavone, The Graduate Center, City University of New YorkFollow

Date of Degree

2-2024

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Ryan Murelli

Committee Members

Wayne Harding

Shengping Zheng

Subject Categories

Organic Chemistry

Keywords

Oxidopyrylium cycloaddition, troponoid, ylide, oxidopyrylium dimer

Abstract

Herein, we describe our efforts to investigate mechanistic considerations of oxidopyrylium ylides and their use in cycloadditions to form complex bicyclic structures and the advancement of these cycloadducts to the synthesis of densely functionalized tropolones. This work also describes applications of tropolones as biologically relevant structures and dynamic fluorophores.

In Chapter 1, we expand upon previous studies done in the Murelli Lab describing the ability of 3-hydroxy-4-pyrone derived oxidopyrylium dimers to revert back to ylides in situ and as result can be used as a clean oxidopyrylium ylide source in accessing oxabicyclic compounds. Intermolecular cycloadditions of these ylides can be limited due to competing dimerization processes, and consequently high equivalents of dipolarophiles are usually used to help intercept the ylide prior to dimerization. In Chapter 1, we show that intermolecular cycloaddition reactions between 3-hydroxy-3-pyrone-derived oxidopyrylium dimers can be done with stoichiometrically equivalent ratios of alkyne dipolarophiles under thermal conditions. These studies describe how when highly reactive alkynes are used the reaction is completely atom economical. When less reactive alkynes are used, dimer rearrangement products are a main byproduct. Finally, when highly volatile alkynes are used, competing 2:1 ylide-to-alkyne products are observed in good yields with exquisitely high regio- and stereo- selectivity that is unique based upon the source of oxidopyrylium ylide.

One application of the bicyclic structures formed from oxidopyrylium cycloadditions is their conversion to 7-hydroxytropolones and 3,7-dihydroxytropolones via an acid mediated ring opening and demethylation strategies, a synthetic route discovered previously in our lab. In Chapter 2, we continue these synthetic studies to the advancement of 3,7-dimethoxytropolones and isomeric 3-hydroxy-7-methoxytropolones through complementary benzyl alcohol incorporated procedures. This allowed for the in-depth analysis and comparison amongst these classes of tropolones in their antiviral activity against herpes simplex virus -1, and hepatitis B virus.

An underexplored property of hydroxytropolones is their unique fluorescent profile. In Chapter 3, we describe the synthesis of lactam-fused tropolones, initially designed to continue building a library for biological studies, via rapid annulation between appropriately functionalized tropolones and primary amines. While working towards these structures, we synthesized novel lactam-fused tropolones that had dynamic fluorescent properties. Specifically, they displayed fluorescence emission across a broad range of visible light range simply by changing the source of amine. These troponoid fluorophores are also highly responsive to changes in solvent and pH, as well as the presence of divalent metal ions giving them potential to be new tool molecules with value to the scientific community.

Recommended Citation

Schiavone, Daniel V., "Studies of Oxidopyrylium Ylide Dimers and Their Utility in the Synthesis of Densely Functionalized Troponoids" (2024). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/5710