Date of Award
2018
Publisher
North Dakota State University
Document Type
Dissertation
Degree Awarded
Doctor of Philosophy (PhD)
Department
Chemistry and Biochemistry
College
Science and Mathematics
Faculty Advisor
Cook, Gregory R.
Description
The central core of many biologically active natural products and pharmaceuticals contain N-heterocycles, the installation of simple/complex functional groups using C-H/N-H functionalization methodologies has the potential to dramatically increase the efficiency of synthesis with respect to resources, time and overall steps to key intermediate/products. Transition metal-catalyzed functionalization of N-heterocycles proved as a powerful tool for the construction of C-C and C-heteroatom bonds. The work in this dissertation describes the development of palladium catalyzed allylation, and the transition metal catalyzed C-H activation for selective functionalization of electron deficient N-heterocycles. Chapter 1 A thorough study highlighting the important developments made in transition metal catalyzed approaches for C-C and C-X bond forming reactions is discussed with a focus on allylation, directed indole C-2 substitution and vinylic C-H activation. Chapter 2 describes the development of a selective Tsuji-Trost allylation reaction of electron deficient heterocycles. The key issues addressed in this chapter include an extensive investigation of mechanistic details, and factors influencing selectivity control of tautomerizable heteroarenes to form linear N-allylated products. Chapter 3 describes the oxidative allylic C-H amidation reaction of N-heterocycles, an efficient and atom economic variant of traditional allylation. A simple protocol avoiding the use of expensive catalysts/ ligands or additives for allylation of N-heterocycles is demonstrated. Mechanistic investigation indicated the importance of Pd(II)/DMSO catalytic system for the allylic C-H activation, allowing for the efficient synthesis of π-allylpalladium chloride catalysts. Chapter 4 describes a detailed investigation on the development of an unusual π-bond directed indole C-2 amidation. A mechanism-based reaction optimization, and comparison of effectiveness of both Pd and Ni catalyst system indicated the effectiveness of NiCl2 for the π-bond directed indole C-2 substitution. Mechanistic studies also shed light on the dual role of solvent system (DCE: DMSO), acting both as ligand (DMSO) and as an oxidant (DCE) for the regeneration of active Ni(II) catalyst. Chapter 5 describes the development of a ruthenium catalyst system for the synthesis of fused quinazolinones via vinylic C-H/amide N-H bond activation/alkyne annulation. This chapter also describes the utilization of quinazoline core as a masked pyridine template for the synthesis highly substituted pyridines via amide alcoholysis.
Recommended Citation
Vemula, Sandeepreddy, "Functionalization of Heterocycles: A Metal Catalyzed Approach via Allylation and C-H Activation" (2018). Chemistry and Biochemistry. 83.
https://digitalcommons.ndsu.edu/chem-biochem/83
Rights
NDSU Policy 190.6.2
Rights Link
https://www.ndsu.edu/fileadmin/policy/190.pdf
Author ORCID Identifier
0000-0001-7604-856X
Handle Identifier
https://hdl.handle.net/10365/29016