Dissertations, Theses, and Capstone Projects
Date of Degree
2-2025
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy
Program
Chemistry
Advisor
Qiao-Sheng Hu
Committee Members
Mark Biscoe
Shi Jin
Subject Categories
Organic Chemistry | Polymer Chemistry
Keywords
Transition Metal, Suzuki Cross-Coupling Reactions, Suzuki Cross-Coupling Polymerization, Addition Reactions, Curcumin, Methotrexate, Antitumor
Abstract
Development of new synthetic methods for organic compounds is one of the most critical endeavors in modern chemistry. This pursuit not only broadens the scope of chemical synthesis but also provides valuable tools for various applications in pharmaceuticals, materials science, and so on.
My research can be divided into two main parts. The first part focuses on the development of synthetic methodologies of transition metal-catalyzed reactions. Transition metal-catalyzed carbon-carbon bond-forming reactions, such as Suzuki coupling reactions and addition reactions, are among the most powerful and versatile transformations in organic synthesis. My work is centered on integrating these highly efficient reactions in a sequential or tandem fashion and aims to access novel compounds that are otherwise challenging or impossible to synthesize through conventional methods.
Aryl boronic acid/acid esters, which are products of Miyaura borylation, also serve as substrates in transition metal-catalyzed addition reactions. This dual functionality provides an opportunity for a sequential/tandem synthetic process. Based on the hypothesis that the second addition reaction could proceed without the need for separation and purification of aryl boronic acids/acid esters from the initial Miyaura borylation, we developed a sequential Miyaura borylation–transition metal-catalyzed addition reaction in Chapter 2.
According to our understanding of transition metal-catalyzed addition reactions, we explored the tandem transition metal-catalyzed 1,4-addition–1,2-addition of arylethylene-1,2-diboronic acid bis(pinacol) ester. This research developed a new synthetic method for cyclic 2-aryl-4-alkylcyclopent-2-en-1-ol derivatives. Slight stereoselectivity was observed in the product and a plausible pathway was proposed to explain the observed stereochemical outcomes in Chapter 3.
The Suzuki cross-coupling reaction has emerged as a powerful and versatile tool for organic synthesis. Our group has synthesized open-chain polymers through AA/BB-type Suzuki cross-coupling polymerization catalyzed by palladacycle precatalyst. Building on this success, we sought to explore whether cyclic polymers could also be synthesized under similar reaction conditions. Using 1,2-dibromo-4,5-bis(alkoxy)benzene and 9,9-dialkyl-2,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-fluorene as the monomers, we adjusted the substrate feed ratio and concentrations, which facilitated the synthesis of cyclic poly(arene)s in Chapter 4.
All the sequential/tandem transition metal-catalyzed reaction protocols above offer us rapid entry to synthesize complex compounds from simple precursors.
The second part of my research focuses on the synthesis of a prodrug combining two antitumor molecules, methotrexate and curcumin. The initial attempt to directly connect these two molecules via an ester bond proved unsuccessful due to their chemical incompatibility, leading to decomposition of the adduct during synthesis. To address this challenge, a dodecanoic linker chain was introduced to spatially separate the methotrexate and curcumin moieties. This approach effectively stabilized the adduct, allowing for the successful synthesis of the methotrexate-dodecanoic-curcumin DCU adduct. The introduction of the linker not only resolved the compatibility issues but also offered additional advantages, such as enhanced solubility, and potentially improved bioavailability and better pharmacokinetic properties.
Recommended Citation
Li, Hanbin, "Development of New Synthetic Methods for Transition Metal-Catalyzed Organic Reactions and Synthesis of Curcumin-Based Adducts" (2025). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/6092
