Date of Award


Degree Type


Degree Name

Doctor of Philosophy



First Advisor

M. Mahmun Hossain

Committee Members

M. Mahmun Hossain, Alexander Arnold, Mark Dietz, Arsenio A. Pacheco, Xiaohua Peng


3, 3′-disubstituted Oxindole, All-carbon Quaternary Carbonyl Compounds, Asymmetric Allylic Alkylation, Asymmetric Catalysis, Palladium, Α-disubstituted Quaternary Β-lactone


The development of catalytic, enantioselective methods for the construction of all-carbon quaternary stereocenters is an outstanding achievement in the recent history of organic chemistry. The palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) reaction has played a key role in creating such stereocenters and has allowed researchers to synthesize a vast number of biologically potent natural products. However, synthetic methodologies to access compounds containing α-aryl groups to the quaternary carbon stereocenters are still rare. The increasing appearance of these all-carbon α-aryl quaternary stereocenters in a growing number of biologically active natural products and pharmaceutical agents creates a pressing need for the ability to construct this important motif enantioselectively.

In this endeavor, a set of acyclic all-carbon α-aryl quaternary stereocenter has been synthesized via intermolecular Palladium catalyzed Asymmetric Allylic Alkylation (Pd-AAA). Here hydroxyacrylate was used as an unprecedented nucleophilic counterpart instead of the widely used ketonic substrate. This produced a very rare all-carbon quaternary aldehydes with good to excellent yields (75–99%) and enantioselectivities ranges between 75–94%. This methodology is not only limited to produce aldehydes, as an analogous ketone with a quaternary α-carbon center has also been synthesized successfully.

Using this methodology, chiral 3,3′-disubstituted oxindole moiety was produced with high yield (80%) and enantioselectivity (82%) from o-nitrophenylhydroxyacrylate in three simple steps. The oxindole framework bearing a tetrasubstituted carbon stereocenter at 3-position is a privileged heterocyclic motif that constructs the core of a large family of bioactive natural products and a series of pharmaceutically active compounds. An intensive research has been conducted to synthesize 3,3′-disubstituted oxindole which resulted in a fair amount of methods to produce such an important moiety. However, to the best of our knowledge, all of the reported methodologies so far have used pre-formed oxindole ring itself or a highly specialized compound as a prochiral starting material to produce asymmetry. Another application of this method includes the synthesis of chiral α-disubstituted quaternary β-lactone from the parent phenylhydroxyacrylate in high yield (87%) and enantioselectivity (94%). β-lactones have recently emerged as important synthetic targets due to their occurrence in a variety of natural products, their utility as versatile synthetic intermediates, and their use as monomers for the preparation of biodegradable polymers.