Chemoselective and Stereoselective Exploration of the Chemical Reactivity Space of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application to the Synthesis of Aza-Polycyclic Architectures

The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an <em>N</em>-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (<em>e.g.</em>, Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition metal-free and occurs at room temperature will also be discussed.

Name thesis:degree_name

Master of Science (MS)

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2017

Author dc:creator

• Mansker, Brandon Joseph

Contributors dc:contributor

• Timothy K. Beng
• Levente Fabry-Asztalos
• Gil Belofsky

• organic
• heterocycle
• synthesis
• DOS
• intermediates
• Chemical Actions and Uses
• Heterocyclic Compounds
• Medicinal and Pharmaceutical Chemistry
• Organic Chemicals
• Polycyclic Compounds

Language dc:language

English

Repository record dc:identifier

https://digitalcommons.cwu.edu/etd/704

OAI identifier oai:identifier

oai:digitalcommons.cwu.edu:etd-1712