Palladium Catalyzed Carbon Carbon Bond Formation Under Reductive Oxidative And Redox Neutral Conditions PDF Download

"This thesis describes the design and development of reductive amination methodologies of unactivated carbon-oxygen bonds using palladium on charcoal as a heterogeneous catalyst. The underlying premise is the transformation of starting materials that can be obtained from bio-renewable resources into commodity chemicals. Specifically, 2-cyclohexen-1-one and phenol were used as lignin building-block surrogates for C-N bond formation. The first chapter places the work developed in this thesis both in a global and a scientific context. Its objective is to provide an overview of our societal needs while describing the latest scientific developments related to this thesis topic. Thus, it begins by exploring the United Nation's Sustainable Goals, followed by an overview of petroleum and lignin chemistry, and finishes with a review on amino acid N-modification. In chapter two, the development of a novel methodology for the N-arylation of [alpha]-amino acids using 2-cyclohexen-1-one is described. Palladium on carbon was chosen as the catalyst, and several reaction conditions were explored to obtain optimal yields. This methodology's attractiveness lies in the absence of an aryl halide or protecting group on the 2-cyclohexen-1-one for the N-arylation to proceed. The reaction requires substoichiometric amounts of base and oxygen as the terminal oxidant. Aliphatic amino acids were ideal substrates for the reaction, and cyclohexanone provided the N-biarylated amino acids in good yields (up to 74%). Chapter three describes efforts to improve the harsh conditions required for the N-arylation of [alpha]-amino acids, resulting in the development of a novel methodology for their N-cyclohexylation in water, at room temperature, using phenol as a coupling partner. The reaction successfully achieves N-cyclohexylation for 17 out of the 20 naturally occurring amino acids without racemization with up to quantitative yields. Furthermore, small peptides were also successful substrates for the reaction. The fourth chapter explores the possibility of applying the latter methodology for the formation of one- and two-component peptide staples using tyrosine as a handle. The one component staple was investigated using acetyl-lysine and acetyl-tyrosine, while the two-component staple was investigated using acetylated-tyrosine 2,2'-(ethylenedioxy)bis(ethylamine). While model substrates proved to couple successfully under previously optimized conditions, concentration and characterization proved to be challenging for working with larger peptides. Additional experiments exploring the possibility of using tyrosine amination as a pH responding hydrogel are also described in this chapter. Finally, chapter five explores the possibility of synthesizing diphenylamines from phenol and ammonia formate as a convenient ammonia surrogate. Seventeen different diarylamines were synthesized with palladium on charcoal as the catalyst, with yields ranging from good to excellent. Notably, water and CO2 were the only byproducts generated from this transformation. Triphenylamine was also obtained in combination with the methodology described in Chapter 1"--