Uniform TitlePd/C-catalyzed Suzuki cross- and self- couplings & the development of a lab-scale hydrogenation system
NameChen, Jeng-Shiou (author), Khinast, Johannes (chair), Pedersen, Henrik (internal member), Ierapetritou, Marianthi (internal member), Krogh-Jespersen, Karsten (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectChemical and Biochemical Engineering,
DescriptionSuzuki couplings have become an efficient and clean strategy for the preparation of biologically active functionalized biphenyls, which are important building blocks for pharmaceutical and agricultural compounds. Among all catalysts of choice for Suzuki couplings, palladium on carbon (Pd/C) is most frequently used for industrial applications due to its high catalytic activity, low cost and easy removal from the reaction mixture. Using a model coupling reaction of biphenylacetic acid, we intended to provide a thorough understanding of Pd/C-catalyzed Suzuki couplings for a straightforward industrial implementation.
A detailed investigation of the reaction parameters was carried out in Chapter 2. The experimental observations indicate that excess amount of the borate is helpful to accelerate the reaction and 2 moles eq. of a strong base is the best choice for the reaction. Furthermore, our results suggest that transmetalation is the rate-limiting step of the Pd/C-catalyzed Suzuki couplings and also show that [OH-] is a critical factor affecting the reaction rate.
In Chapter 3, the mechanism of Pd-leaching from Pd/C was investigated. The filtration test was used to prove that oxidative addition of aryl-bromides is the main cause for Pd-leaching, which is independent of the reaction solvent and temperature. In addition, the oxidative addition of aryl-borates is another cause for Pd-leaching. PVPy adsorption studies suggest that the activity of Pd/C is mainly due to leached Pd. Furthermore, PVPy was proven to be a good reagent for complete removal of Pd-residuals from the reaction mixture.
In Chapter 4, homocoupling of arylboronic acids was successfully carried out with Pd/C in water/2-propanol (9:1 in volume ratio) under air, to obtain symmetric biaryls in good yield. This novel system was discovered during Pd-leaching studies and optimized in our work. The experimental observations suggest that higher water fractions in the co-solvent and higher reaction temperature are beneficial for the reaction. DFT calculations suggest that the overall reactivity of the different arylboronic acids is independent of the oxidative addition of Pd to the arylboronic acid.
Lastly, we successfully established a lab-scale hydrogenation system at Rutgers University to carry out chiral hydrogenation, which is presented in Chapter 5. The system allows reactions operated under 120 bars at a wide range of reaction temperatures (-80~350??C).
NoteIncludes bibliographical references (p. 116-122).
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
RightsThe author owns the copyright to this work.