Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


DuvvuriThesis-Chemistry2018.pdf (53.29 MB)

ETD Abstract Container

Abstract Header

Transition Metal Catalyzed Enantioselective Hydroboration and Hydrovinylation of Alkenes

Duvvuri, Krishnaja
http://rave.ohiolink.edu/etdc/view?acc_num=osu1524049349604356

Abstract Details

2018, Doctor of Philosophy, Ohio State University, Chemistry.
Economic methods to stitch feedstocks onto molecules using chemical synthesis can greatly impact the design and manufacture of molecules, from medicine to materials. For example, olefins, one of the most abundantly obtained class of feedstocks from the petroleum refining industry, are starting carbon units for many of the processes used to produce value-added chemicals in the pharmaceutical, agrochemical and polymer industry. However, many of these processes are often limited with harsh reaction conditions, poor yields and low selectivities. Organic chemists have long been trying to address the unmet challenges in this field; to simultaneously activate and functionalize olefins under mild reaction conditions, with the desired level of precision and selectivity, bond-by-bond, in order to access high value-added molecules from cheap and abundant lower alkenes. My graduate research work focusses on developing methods to address the challenges in olefin activation by employing transition metal catalysts as powerful tools. Mimicking nature’s enzymes and its extra-ordinary selectivity, we seek to address olefin functionalization, more specifically carbon-boron and carbon-carbon bond forming reactions, which could provide a powerful means to access a broad range of advanced, highly functionalized target molecules of interest to medicinal chemistry and related areas. We seek to develop a highly efficient catalytic protocol using the earth abundant metal, cobalt, linked to suitable ligands, to achieve the hydroboration of unactivated olefins to obtain organo-borane products with desired level of yield and selectivity. Although these are highly versatile compounds having wide synthetic utility as pharmaceutical intermediates, there is a paucity of methods to make organo-boranes directly from feedstocks. In this research methodology, a systematic investigation of diverse classes of ligand-cobalt complexes was performed to activate unactivated olefins. Based on mechanistic insights and experimental observations, the ligands were optimized to get the best selectivity of the desired value-added products from substituted dienes. The parameters effecting yields such as organic solvents, temperature and catalyst loading were also examined to process the best yields. The operationally simple, yet unprecedented reactions we discovered expand the realm of hydrofunctionalizations to provide direct access to a number of boranes, of interest in organic synthesis. The resulting boron compounds were further transformed into several chiral building blocks, thus expanding the scope of the primary process for advanced synthesis. -aryl--aminobutyric acid (GABA) derivatives are a large class of medicinally active compounds, examples of which include (R)-Baclophen and (R)-Rolipram. Methods for the efficient enantioselective synthesis this class of compounds were explored through the asymmetric hydrovinylation reaction, the addition of ethylene to olefins. By employing finely tuned chiral nickel complexes, several -substituted styrenes of relevance were found to undergo hydrovinylation in good to modest enantioselectivites. Model subtstrates were further transformed into the GABA precursor illustrating that this class of medicinally active compounds can be accessed from simple starting materials using the hydrovinylation reaction. We expect that the discoveries like this will shorten the considerable distance between the conceptualization of a molecule as a drug candidate and its large-scale synthesis. Beyond this transformation we anticipate that this reactivity will inspire further advances in olefin functionalization.
T. V. RajanBabu (Advisor)
Jon Parquette (Committee Member)
David Nagib (Committee Member)
523 p.
Chemistry; Organic Chemistry

Recommended Citations

Citations

  • Duvvuri, K. (2018). Transition Metal Catalyzed Enantioselective Hydroboration and Hydrovinylation of Alkenes [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1524049349604356

    APA Style (7th edition)

  • Duvvuri, Krishnaja. Transition Metal Catalyzed Enantioselective Hydroboration and Hydrovinylation of Alkenes. 2018. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1524049349604356.

    MLA Style (8th edition)

  • Duvvuri, Krishnaja. "Transition Metal Catalyzed Enantioselective Hydroboration and Hydrovinylation of Alkenes." Doctoral dissertation, Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1524049349604356

    Chicago Manual of Style (17th edition)

osu1524049349604356
99
© 2018, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.