A Diversity-Oriented Synthesis Approach to Functionalized Azaheterocycles using Cyclic Alpha-Halo Eneformamides

Author

Spencer A. Langevin, Central Washington UniversityFollow

Document Type

Thesis

Date of Degree Completion

Spring 2017

Degree Name

Master of Science (MS)

Department

Chemistry

Committee Chair

Timothy K. Beng

Second Committee Member

Levente Fabry-Asztalos

Third Committee Member

Gil Belofsky

Abstract

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of α-halo enamines/enamides. The synthetic utility of the method is exemplified through the construction of quaternary cyclic propargylic and homoallylic amines, polycyclic lactams, as well as chiral dihydro 1,4-oxazines and thiazines. Given the generality of the approach, we are confident that the synthesis and medicinal chemistry communities will undoubtedly embrace it, thus, endowing it with a practical advantage over existing methodologies.

Recommended Citation

Langevin, Spencer A., "A Diversity-Oriented Synthesis Approach to Functionalized Azaheterocycles using Cyclic Alpha-Halo Eneformamides" (2017). All Master's Theses. 779.
https://digitalcommons.cwu.edu/etd/779

Language

English