Degree

Doctor of Philosophy (PhD)

Department

Department of Chemistry

Document Type

Dissertation

Abstract

The purpose of this dissertation is to describe the efforts undertaken to develop synthetic methodology targeting δ-valerolactone and isocoumarin. At the onset, an introduction to the δ-valerolactone and isocoumarin is given. Relevant examples of δ-valerolactone being utilized in the production of materials of biological and industrial application are then discussed. Following, current methods for forming δ-valerolactone are presented. After, an introduction to isocoumarin is begun. Current methods for producing isocoumarin are then discussed.

The results and discussion section of this dissertation will focus on two methods that were explored with the goal of producing α-acyl-δ-valerolactone with two different substitution patterns. These patterns are the dihydro-2H-pyran-2-ones and the 3-acetyltetrahydro-2H-pyran-2-ones. From the effort developing a method for the construction dihydro-2H-pyran-2-ones, valuable information regarding reactivity of acyl Meldrum’s acid with β-hydroxy carbonyls in various solvents was gleaned. Although efforts at dihydro-2H-pyran-2-ones did not produce the desired motif, results from this hypothesis were implemented in optimizing a successful method.

A method was developed that implements a diastereoselective cascade reaction to construct highly functionalized 3-acetyltetrahydro-2H-pyran-2-ones and isocoumarin. Thermal degradation of acyl Meldrum’s acid derivatives followed by nucleophilic capture with δ-hydroxyeneone resulted in a malonate ester that was cyclized. Intramolecular Michael addition facilitated furnished highly substituted 3-acetyltetrahydro-2H-pyran-2-ones. Electronics of the remote δ’-carbonyl carbon was found to highly effect the epimerizability of the α-acyl group. When the described motif’s δ’-carbon contained an aromatic substituent, a secondary cyclization occurred under the same conditions resulting in isocoumarin related structures. A proposed reaction mechanism is discussed that accounts for the observed stereochemistry. Further exploration of this chemistry is centered on developing a method that would allow for isocoumarin formation without specific structural qualifications of the starting material. This reaction is currently being optimized.

In the final chapter, relevant procedures for the production of materials are presented. Additionally, characterization data is discussed, and crude 1H NMR data is introduced for material in which crude diastereoselective ratios were determined.

Date

3-17-2021

Committee Chair

Kartika, Rendy G.

Available for download on Friday, March 11, 2022

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