Date Approved
2024
Degree Type
Open Access Senior Honors Thesis
Department or School
Chemistry
First Advisor
Maria C. Milletti, Ph.D.
Second Advisor
Hedeel Guy Evans, Ph.D.
Third Advisor
Harriet A. Lindsay, Ph.D.
Abstract
N-heterocycles are the major component of various bioactive natural products, pharmaceuticals, and their precursors. In particularly, β-carbolines are examples of substituted indole and its derivatives that serve as the basic structures of diverse, therapeutically important molecules with broad pharmacological properties. Rajasekar and Anbarasan have suggested a novel one-pot synthesis for dihydro-β-carbolines involving more than one catalytic system: a rhodium acetate dimer for C-H insertion on the indole and a basic organo-catalyst for the subsequent aza-Michael addition. The product can be obtained enantioselectively by using a chiral squaramide as the organo-catalyst. Since the mechanism of this reaction, including the rate determining step, has not been explored by either experimental or computational methods, the purpose of this study is to model the catalytic cycle and delineate the energetics of the reaction pathway. We have determined the structure of all intermediates and several transition states and calculated relative activation barriers using density functional theory (DFT) methods as implemented in the Gaussian suite of programs. We find that the nitrogen extrusion step has the highest activation barrier of those determined so far.
Recommended Citation
Wasiuddin, Syed, "Synthesis of dihydro-β-carbolines by tandem C-H activation and aza-Michael reaction in the presence of Rh(II)/squaramide catalysis: Investigation of the mechanism via computational methods" (2024). Senior Honors Theses and Projects. 802.
https://commons.emich.edu/honors/802