Doctor of Philosophy (Ph.D.)
Degree Granting Department
Jon Antilla, Ph.D.
James Leahy, Ph.D.
Wayne Guida, Ph.D.
Jianfeng Cai, Ph.D.
asymmetric catalysis, organocatalysis, chiral alkaline earth metal phosphate, oxazolidines, oxazinanes, hemiaminals, desymmetrization, dynamic kinetic resolution
Small molecule hydrogen bond donors have emerged as versatile catalysts in asymmetric synthesis. Within this class, chiral BINOL phosphoric acid is regarded as one of the pioneer catalysts used in several asymmetric transformations. The ability of the catalyst to activate the substrates could be controlled in two different ways. (1) Dual activation/bifunctional activation of substrate by hydrogen bond interactions or ion pairing with phosphoric acid or (2) By forming chiral BINOL phosphate metal complex that could significantly alter the interactions in chiral space. In particular, chiral alkaline earth metal phosphate complexes have unique advantages as catalysts owing to the ubiquitous availability of alkaline earth metals, strong Brønsted basicity of their counterions, mild but significant Lewis acidity of the metal and their ability to coordinate at multiple reactive sites due to large ionic radius.
Chapter 1 summarizes the recent development of alkaline earth metal complexes in asymmetric catalysis. My thesis dissertation is focused on the application of chiral alkaline earth metal phosphate complexes in novel asymmetric reactions.
In Chapter 2, we disclosed an efficient asymmetric one-pot synthesis of chiral 1,3-oxazolidines and chiral 1,3-oxazinanes. Chiral oxazolidines and oxazinanes are widely used as auxiliaries in asymmetric transition metal catalysis and also key structural motifs in natural products with biological activities. We developed a new synthetic method for chiral 1,3-oxazolidines which follows the enantioselective addition of alcohols to imines catalyzed by chiral 3,3’-(triisopropylphenyl)-derived BINOL magnesium phosphate to form hemiaminal intermediate, which then undergoes mild base mediated intramolecular nucleophilic substitution to afford highly enantioselective 1,3-oxazolidines and 1,3-oxazinanes in good yields.
In Chapter 3, we developed the first catalytic enantioselective desymmetrization process for the synthesis of novel axially chiral cyclohexylidene oxime ethers. Even though these molecules were found to be optically active in 1910, methods to synthesize these molecules are scarce. We have developed an efficient desymmetrization process of 4-phenyl cyclohexanones with phenoxyamines catalyzed by chiral BINOL strontium phosphate complex to afford highly enantioselective products. We then extended this methodology to the dynamic kinetic resolution of 2-substituted cyclohexanones to form chiral 2-substituted cyclohexyl oximes in good enantioselectivities, as demonstrated in Chapter 4. We further demonstrated the utility of these compounds by converting them to chiral 2-aryl cyclohexylamines which are important synthetic intermediates.
Scholar Commons Citation
Nimmagadda, Sri Krishna, "Asymmetric Transformations Catalyzed By Chiral BINOL Alkaline Earth Metal Phosphate Complexes" (2016). Graduate Theses and Dissertations.