Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.



Degree Program

Chemistry, PhD

Committee Chair

Handa, Sachin

Committee Co-Chair (if applicable)

Luzzio, Frederick A.

Committee Member

Luzzio, Frederick A.

Committee Member

Dr. Farshid Ramezanipour

Committee Member

Jasinski, Jacek

Author's Keywords

sustainable chemistry; green chemistry; micellar catalysis; peptide synthesis; fluorinations; nanoparticles


Water is stable, benign, and green solvent. Its usage as a solvent in organic synthesis is significantly enhanced by micellar catalysis. However, replacing water as a reaction medium in organic synthesis is not sufficient to meet the sustainability challenges—excessive organic solvents are still required for product isolation and purification. Notably, solvents used in syntheses contribute to more than 80% of waste generation. In addition to solvents, the use of palladium in large amounts is also a problem for the future as it is a precious, low-abundance metal, and its supply is dwindling. Therefore, this dissertation highlights the various sustainable protocols for minimization of the usage of solvents, incorporation of nanocatalysis using earth-abundant first-row transition metals, and development of highly selective protocols for amide couplings, cycloaddition reactions, cross-couplings, and monofluorination of N-heterocycles respectively. Chapter 1 reviews the importance of Green and Sustainable Chemistry, highlighting its impact on the cost and waste reductions in various industrial organic transformations. It also includes the concept of micellar catalysis (reaction in water) in combination with nanocatalysis for efficient cross-couplings. Moreover, the future directions and present challenges in the field of green chemistry are emphasized. Chapter 2 discusses the development of a novel protocol for the monofluorination of bioactive N-heterocycles. The current methodology suffers from low yields with the formation of genotoxic byproduct (with a permissible limit of Chapter 3 highlights an unprecedented methodology for the selective monofluorination of unprotected indoles under mild aqueous conditions. The methodology is easy to execute and does not require the use of toxic organic solvents or rare-earth metals. High selectivity towards monofluorinations was achieved on a broad range of substrates, including the synthesis of intermediates of bioactive molecules. Chapters 4 & 5 discuss the sustainable protocol for the amide couplings in water. It highlights the use of our designer surfactant PS-750-M, which structurally mimics toxic dipolar-aprotic organic solvents like DMF, DMAc, and NMP. PS-750-M along with coupling agent forms mixed micelles, which enable ultrafast amide couplings in water. The most common coupling agent used in amide couplings is 1-Ethyl-3-(3-(dimethylamino)propyl)-carbodiimide (EDC•HCl). It has both lipophilic and hydrophilic regions allowing its self-aggregation in an aqueous medium containing PS-750-M to form mixed micelles. These mixed micelles provide a very high local concentration of reactants, resulting in ultrafast reaction rates without product epimerization. The methodology completely avoids the use of toxic organic solvents as the product spontaneously extrudes out of micelle, allowing its isolation by simple filtration. Chapter 6 describe the use of sustainable and inexpensive Cu(I) catalysis for cycloadditions. Notably, spontaneous oxidation of Cu(I) to Cu(II) adversely affects the reaction efficiency. We developed a catalytic methodology that uses Cu(II) nanomaterial, light, and azide. The irradiation triggers the single electron transfers from azide to Cu, generating Cu(I) species within the micelles to enable powerful cycloaddition chemistry via Cu(I) catalysis. Nanomaterial was characterized using XAS, HRTEM, NMR, UV-Vis, and IR spectroscopy. Chapter 7 discusses a completely organic solvent-free technology for copper-catalyzed cycloadditions, using a benign cellulose-based polymer, hydroxypropyl methylcellulose (HPMC). The unique hydrophobic pockets of HPMC enable the formation of ultrasmall water-stable Cu(I) NPs which was used for the fast organic solvent-free cycloadditions in water. Chapters 8 & 9 describe the development of new (bi)trimetallic nanoparticles (NPs). These NPs exhibit the synergy between two or more metals that enable powerful, sustainable, and selective catalysis. The bimetallic NPs of Cu and Mn, as well as trimetallic NPs of Cu, Mn, and Pd (ppm level) enable selective Suzuki-Miyaura cross-coupling, hydroboration and hydrosilylation of alkenes, alkynes, and chalcones. All these transformations were carried out under mild aqueous conditions. Chapter 10 highlights the synthesis of metal-free organic polymer and its applications in the E to Z isomerization of olefins. The photocatalyst is highly recyclable (up to 4 cycles). The methodology was also extended for the esterification of aldehydes and oxidations of alcohols under aqueous medium.