Date on Master's Thesis/Doctoral Dissertation

8-2021

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Chemistry

Degree Program

Chemistry, PhD

Committee Chair

Handa, Sachin

Committee Co-Chair (if applicable)

Thompson, Lee

Committee Member

Satyavolu, Jagannadh

Committee Member

Gorce, Andrea

Author's Keywords

Micellar catalysis

Abstract

Water is considered a green, sustainable, and inexpensive solvent for organic synthesis. However, performing organic reactions in water is especially challenging due to the inherent insolubility of substrates and catalysts. Inspired from Nature, where chemistry happens in water, micellar catalysis has recently gained much attention, especially for applications in pharmaceutical industry. Aqueous micelles are generally formed by amphiphile`s self-aggregation, a particular class of molecules possessing both hydrophobic and hydrophilic components. The aqueous micelle contains a hydrophobic cavity, which allows the lipophilic substrates and catalyst to go inside micelles, allowing their much higher localized concentration that enhances the reaction rates and improves the purity profile. In this direction, our group has developed a proline-based amphiphile PS-750-M that mimics dipolar-aprotic solvents, such as DMF, DMAc, and NMP. Under the environment of micelles of PS-750-M, various valued organic transformations were effectively achieved in aqueous conditions, especially the transformations involving unstable reaction intermediates. Carbene is an important reaction intermediate in many organic transformations. However, it is highly water-sensitive, and reactions involving this intermediate usually require anhydrous and toxic organic solvents. With our approach, the nanomicelles derived from PS-750-M shield the in-situ generated carbene further preventing its dimerization and enable the desired coupling reactions. The sustainability of the reaction system is demonstrated by the recyclability of both the nanoparticle catalyst and the micellar reaction medium at variable reaction scales. Likewise, to explore the reactivity of persistent radicals under micellar conditions, a heterogeneous Cu-based catalyst has been developed and employed for the oxidation of benzylic alcohols to aldehydes in water under mild conditions. A broad substrate scope, excellent selectivity, and no over-oxidation reveal the catalyst robustness. In addition, the catalyst is entirely recyclable and reuse without significant loss in activity after three cycles. Additionally, trimetallic nanoparticles are developed to enable selective Suzuki-Miyaura (SM) couplings of aryl boronate esters and aryl halides containing terminal olefins. Generally, these substrates participate in the Heck coupling reaction to generate unwanted polymeric and other byproducts. However, no byproducts were observed under our micellar conditions. This technology provides a mild and valuable access to diverse functionalized styrene-type molecules. Finally, although hydroboration of terminal alkynes in aqueous conditions are well documented, the hydroboration of unsymmetrical internal alkynes is still underexplored due to poor selectivity. Using simple Cu(OAc)2 with ppm level of Pd(OAc)2 ligated with PCy3, a mild and highly regioselective of 𝛽-hydroboration of unsymmetric internal alkynes has been developed using the aqueous micellar conditions.

Share

COinS