Titanium-catalyzed one-pot multicomponent coupling reactions for direct access to heterocycles

摘要

Titanium-catalyzed multicomponent reactions have been utilized in the synthesis of various heterocycles and natural products. In this research further applications of titanium-catalyzed multicomponent reactions towards the synthesis of nitrogen containing heterocycles are investigated. The first part of the thesis discusses the development of novel titanium complexes bearing the 2-(2`-pyridyl)-3,5-dimethylpyrrole ancillary ligands. This novel titanium catalyst demonstrates the single step synthesis of 1,3-disubstituted pyrazoles can be prepared in a one-pot fashion from terminal alkyne, isonitrile, and monosubstituted hydrazines (Chapter 2). Titanium-catalyzed 3-component coupling of an alkyne, isonitrile, and amine can be used to generate tautomers of 1,3-diimines. These diimines produced in situ undergo cyclization with hydroxylamine hydrochloride, glycine ethyl ester hydrochloride and malononitrile in a one-pot procedure to provide isoxazoles (Chapter 3), pyrrole-2-carboxylates (Chapter 4) and aminopyridines (Chapter 5) respectively. Finally substituted quinolines from the acid mediated cyclizations of diimines have also been synthesized. For their biological activity and inhibitions of the 20S proteasome of these substituted quinolines are currently under investigation (Chapter 6).