Graduation Year

2015

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Chemistry

Degree Granting Department

Chemistry

Major Professor

Jon C Antilla, Ph.D.

Committee Member

Wayne Guida, Ph.D.

Committee Member

Shengqian Ma, Ph.D.

Committee Member

Peter Zhang, Ph.D.

Keywords

heterogeneous asymmetric catalysis, metal organic framework, metal organic material, organocatalysis, porous organic material

Abstract

The administration of enantiopure drugs brings advantages such as improved efficacy, more predictable pharmacokinetics and reduced toxicity from the point of view of the pharmaceutical area.[1] For this reason, a tremendous amount of supply and demand for enantiomeric pure compounds has been shown not only in market, but industry and academia.[2-4] According to the industry publication Genetic Engineering and Biotechnology News (GEN) in 2014, 22 billion dollars were accounted for enantiopure form of drugs such as Sovaldi® (Sofosbuvir), Crestor® (Rosuvastatin), and Advair® (fluticasone/salmeterol).

The fact that one enantiomer can be pharmacologically effective whereas the other enantiomer can be inactive or display non-desirable activity, chiral resolution and asymmetric synthesis research has broken out in recent years to obtain one desired stereoisomer. Enormous amounts of well-organized and rationalized research results for higher enantiomeric selectivity and efficiency has been reported with diverse chiral ligands and transition metals in academia.[5-10] However novelty-driven results from academic area does not meet the requirement in industry field for the practical issue, especially tedious separation process that require high cost and effort. In addition, methodologies developed with privileged chiral ligands and transition metal complexes leave a concern like undesired residue of trace amount of toxic metals in the products.

In this dissertation, two types of heterogeneous asymmetric catalyst were investigated to find the alternative that accommodates industrial requirement to obtain enantiomeric pure compounds and novelty-driven academic demands. Firstly, constructions of rationally designed metal organic frameworks (MOFs) using chiral BINOL-derived phosphoric acid ligands were achieved. Overall, catalytic reactions with ocMOFs showed lower enatioselectivity than their homogeneous counterparts, but one of the MOFs, ocMOF-1, was found to exhibit improved enantioselectivity than its homogeneous counterpart in the context of transfer hydrogenation reaction of benzoxazine. Lower enatioselectivity with ocMOFs was rationalized by the chiral environment change by the formation of frameworks in a computational study.

In addition, self-supported heterogenization of chiral BINOL-phosphoric acid was achieved by the Yamamoto coupling reaction, and by using catalytically active ocPOP-1 having nanoscopic channels, enantioselectivity was obtained up to 48% in transfer hydrogenation of N-PMP ketimine. Although extension of substituent groups at 3, 3' positions was expected to bring enhanced steric hindrance and to influence to enantioselectivity positively, lack of spatially well-defined interactions induced by this chiral environment change might have lowered the enantiomeric selectivity of the catalytic reaction using ocPOP-1 than its counterpart.

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