Date of Award

Summer 8-13-2015

Degree Type

Dissertation

Degree Name

PhD. Chemistry

Department

Chemistry and Biochemistry

Advisor

John R. Sowa, Ph.D

Committee Member

Cecilia Marzabadi, Ph.D

Committee Member

David Sabatino, Ph.D

Committee Member

Nicholas H. Snow, Ph.D

Keywords

Green chemistry, asymmetric transfer hydrogenation, allylic alcohol, thermodynamic characterization, enantioseparation, benzyl alcohol

Abstract

Green chemistry has been applied to all aspects of the life cycle of chemically related products, including design, usage, manufacturing, analysis, and disposal. In this thesis, I focus on the green chemistry applications in organic synthesis and analytical chemistry. More specifically, allylic and chiral alcohols are abundant in natural sources such as in essential oils, and widely utilized as starting materials. They are also major components in food, fragrance, biocides and the pharmaceutical compounds. In this thesis, I report the first Ru-catalysed asymmetric transfer hydrogenation (ATH) of prochiral allylic alcohols. This reaction provides chiral secondary alcohols in excellent enantioselectivities and yield. This new reaction is much safer, more economical and environmentally friendly for the asymmetric reduction of allylic alcohols compared to the high-pressure gaseous hydrogenations. Mechanistic studies through a series of deuterium-labeled experiments provided a new mechanism for the ATH reaction. Specifically, a tandem enantioselective isomerization-transfer hydrogenation process occurs. The asymmetric induction step occurs during the Ru-assisted 1,3-hydrogen shift isomerization through an enal intermediate prior to transfer hydrogenation. Reaction conditions were optimized using chiral ruthenium complexes.

The thermodynamic characteristics of the enantioseparation of the chiral benzyl alcohols under ACN-free RP-HPLC were also investigated. The enantiomers of various benzyl alcohols were separated on derivatized cellulose and amylose chiral stationary phases with methanol/water or ethanol/water as mobile phases. Enantioseparation was optimized by varying the percentage of organic modifier and column temperature. Baseline resolution was achieved in 10 min of elution time for most of the selected enantiomers. The effects of the mobile phase composition, column temperature and structural moieties of α-substituents on the enantioseparation were investigated. For all enantiomeric pairs, the experimental van’t Hoff plots (ln k' vs 1/T and ln α vs 1/T) of each mobile phase/stationary phase set were linear in the temperature range between 10 to 40 oC. The corresponding thermodynamic parameters were then calculated. Our studies indicate that chiral separation of benzyl alcohols is controlled by enthalpy. However, bi-aromatic benzyl alcohols showed greater selectivities at higher temperature, indicating that the chiral recognition process is entropy-driven. A linear relationship between changes in enthalpy and entropy, also known as entropy-enthalpy compensation, was observed for all analytes in a wide range of mobile phases. This resulted in relatively constant enantioselectivities under various mobile phase eluting strengths.

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