UVM Theses and Dissertations
Format:
Print
Author:
Bercovici, Daniel A.
Dept./Program:
Chemistry
Year:
2013
Degree:
PhD
Abstract:
At the outset ofthis project it was known that 1-aza-2-azoinaallenes were reactive heteroallene salts that could engage nucleophiles or participate in 1,3-dipolar cycloadditions. The research described herein expands that reactivity profile to include 1-aza-2-azoinaallene salts as reactive intermediates in C-H amination reactions, polar [4 circled plus + 2] cycloadditions, electrophilic aromatic substitutions, and a chloroamination reaction. Our group has utilized this intermediate thus far to prepare structurally complex diazenium salts. The work described in this thesis provides access to pyrazolines, pyrazoles, tetrahydrocinnolines, and pyridazines, which are all biologically active or synthetically useful N-heterocycles. The previous methods of generation and synthetic uses as well as our group's accomplishments with the 1-aza-2-azoniaallene salt intermediate are reviewed.
A novel intramolecular C-H amination reaction is reported from the reaction of [alpha]-chloroazo compounds with Lewis acids. This reaction utilizes 1-aza-2-azoinaallene salt intermediates to react in an intramolecular amination at benzylic, tertiary aliphatic, allylic, and ethereal C-H bonds to prepare a variety of tri-and tetrasubstituted pyrazolines and pyrazoles. Reaction at an enantioenriched chiral center furnished products with complete retention of stereochemical fidelity. Intramolecular competition experiments comparing C-H bonds of different electronic character showed that insertions occur at more electron rich positions. A kinetic isotope effect of 5.0 was observed for an intramolecular deuterium isotope competition experiment. Radical probe studies were inconclusive. All results support 1-aza-2-azoinaallene salts reacting as a nitrenium-like ion by a concerted C-H amination mechanism or a rapid abstraction rebound mechanism.
Tetrahydrocinnolines were preprared through [4 circled plus + 2] cycloadditions of 1-aza-2-azoniaallene with pendant alkenes, generated from the treatment of [alpha]-chloroazo compounds with Lewis acids. The scope of this reaction has been expanded to furnish several tri, and tetracyclic heterocycles with tetrahydrocinnoline motifs, with the formation of quaternary carbon centers in high yield. Experiments suggest this reaction proceeds via a concerted cycloaddition.
A novel intramolecular C-H amination reaction is reported from the reaction of [alpha]-chloroazo compounds with Lewis acids. This reaction utilizes 1-aza-2-azoinaallene salt intermediates to react in an intramolecular amination at benzylic, tertiary aliphatic, allylic, and ethereal C-H bonds to prepare a variety of tri-and tetrasubstituted pyrazolines and pyrazoles. Reaction at an enantioenriched chiral center furnished products with complete retention of stereochemical fidelity. Intramolecular competition experiments comparing C-H bonds of different electronic character showed that insertions occur at more electron rich positions. A kinetic isotope effect of 5.0 was observed for an intramolecular deuterium isotope competition experiment. Radical probe studies were inconclusive. All results support 1-aza-2-azoinaallene salts reacting as a nitrenium-like ion by a concerted C-H amination mechanism or a rapid abstraction rebound mechanism.
Tetrahydrocinnolines were preprared through [4 circled plus + 2] cycloadditions of 1-aza-2-azoniaallene with pendant alkenes, generated from the treatment of [alpha]-chloroazo compounds with Lewis acids. The scope of this reaction has been expanded to furnish several tri, and tetracyclic heterocycles with tetrahydrocinnoline motifs, with the formation of quaternary carbon centers in high yield. Experiments suggest this reaction proceeds via a concerted cycloaddition.