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Synthesis and Ring-Opening Reactions of Bicyclic Alkene-Fused Isoxazolines

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Title: Synthesis and Ring-Opening Reactions of Bicyclic Alkene-Fused Isoxazolines
Author: Nagireddy, Jaipal
Department: Department of Chemistry
Program: Chemistry
Advisor: Tam, William
Abstract: This thesis is an investigation of 1,3-dipolar cycloaddition reactions of nitrile oxides with symmetrical and unsymmetrical bicyclic alkenes, and their subsequent isoxazoline ring opening reactions. Although a large number of 1,3-dipolar cycloaddition reactions between nitrile oxides and bicyclic alkenes have been reported, most of these are currently limited to carbobicyclic alkenes. Introduction of a heteroatom in the bicyclic ring offers differences in the reactivity and selectivity of cycloaddition reactions. Introduction of a substituent at the bridgehead carbon of the bicycloalkene makes the molecule unsymmetrical. The implications of the reduction of symmetry in C1-substituted heterobicyclic rings open the door to regioselectivity studies for these cycloaddition reactions. The stereo- and regiochemical aspects of 1,3-dipolar cycloaddition reactions with acetonitrile oxide and benzonitrile oxide were examined on a wide variety of symmetrical and unsymmetrical oxabicyclic and azabicyclic alkenes. The cycloadditions were found to be completely stereoselective producing only the exo adducts in moderate to excellent yields. In the majority of the cycloaddition reactions, both of the possible regioisomers were produced in varying ratios that depended on electronic and steric effects of the C1 substituent. After having generated numerous isoxazoline derivatives, various metal-catalyzed (Mo, Pd, Zn, Fe and Ni) cleavage conditions were investigated, with successful N-O bond cleavage of isoxazoline rings achieved using Raney-Ni/AlCl3. An N-O bond cleavage, followed by an imine hydrolysis led to the formation of a variety of novel β-hydroxyketone products with moderate to excellent yields. In the early part of this project, a simple and scalable procedure for the preparation of 2-bromofuran was developed. 2-Bromofuran was found to be useful for preparing a series of 2-aryl furans using the Suzuki cross coupling reaction with arylboronic acids. Similarly 2-alkyl furans were prepared using an iron catalyzed cross coupling reaction between 2-bromofuran and alkyl Grignard reagents. The 2-substituted furans were used for the preparation of various C1-substituted oxabicyclic alkenes via the Diels-Alder cycloaddition strategy.
URI: http://hdl.handle.net/10214/8605
Date: 2014-12


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