Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)




John Chisholm


Bobbitt's Salt, Chiral Quinone Catalysts, Oxidation-Bromination Reactions, Oxidative Cyclizations, Pyrroloindoline, Tandem Reactions


In terms of organic chemistry, oxidation reactions are defined as a reaction that results in a product with more π bonds, heteroatoms, and/or rings than the starting compound. These reactions are just one of the conventional types of organic transformations. Although many conditions for the oxidation of organic systems have been developed, it is still a class of reactions that are being investigated in current research. Work described in this document includes the development of two new tandem oxidation reactions and the synthetic design of a catalyst with potential to perform C-H oxidation reactions with enantioselectivity. The first section of this dissertation explores an oxidative cyclization of tryptamine derivatives towards C3a oxygenated pyrroloindolines; compounds that are found in many complex natural products. This investigation utilized 4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate (Bobbitt’s Salt) as a reagent to perform this spontaneous oxidative cyclization. Conditions were optimized and a variety of tryptamine substrates were investigated. N1-protected tryptamines were cyclized in moderate yields. Substitution on the indole ring of the tryptamines was also examined and resulted in the corresponding alkoxyamine-substituted pyrroloindolines. Protection of the indole nitrogen gave substrates that were inert, leading to the conclusion that the indole N-H plays a role in the reaction mechanism. Unfortunately, these conditions were problematic with tryptophan derivatives and resulted in complex diastereomeric mixtures. These oxidative cyclization reactions were utilized in the attempted total synthesis of 3-hydroxy-15H-trytophenalin. The purpose of this synthesis was to determine the stereochemistry of the alcohol group at the C3a position in the isolated natural product. A diastereomeric mixture of alkoxyamine-substituted 3-hydroxy-15H-trytophenalin was obtained with one diastereomer being isolated. Conditions are being investigated to remove the 4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium group to access the C3a hydroxyl group. Once the hydroxy group is unveiled, the NMR spectra of the synthesized product will be compared to the reported spectra to determine the stereochemistry of the isolated natural product. A tandem oxidation-bromination reaction was explored to access brominated unsaturated ketones from aryl allylic alcohols. This led to the development of reaction conditions utilizing TEMPO, Oxone and tetraethylammonium bromide. It is believed this process first proceeds through the oxidation of the allylic alcohol to the vinyl ketone, followed by the dibromination of the alkene. Addition of triethylamine initiates an elimination reaction resulting in the α-bromo-α, β-unsaturated ketone. These conditions were well tolerated by substrates with electron-donating groups on the aromatic ring, but not with electron-withdrawing groups. This may be due to the stronger inductive effect from the substituents. These conditions are limited to aryl allylic alcohols, as alkyl substituted allylic alcohols did not result in product. This method provides rapid access to α-bromo-α, β-unsaturated ketones in a single reaction step, using reagents that are easily handled and shelf stable. In addition to the work described above, the design and synthesis of two new chiral quinone catalysts (CQCs) has been initiated. These catalysts are calculated to be capable of performing enantioselective C-H activation-substitution reactions. We envision one catalyst decorated with two BINOL monoethers, and another functionalized with a single 3,3-diaryl-BINOL molecule. The design of these catalysts is based on a dicyanoquinone core to mimic the reactivity of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), a common organic oxidizing agent. BINOL and BINOL monoether derivatives were envisioned to create a chiral environment around the dicyanoquinone core, with these groups being installed via SNAr chemistry. The synthesis of the chiral dicyanoquinones decorated with two BINOL monoethers was attempted first. The addition of two BINOL methyl ethers proved difficult, as only one molecule was added, even though a variety of conditions were attempted. The synthesis of the CQC with BINOL proved more fruitful, as a double SNAr reaction between BINOL and 2,3,5,6-tetrafluoroterephthalonitrile was accomplished without issue. Conversion of this substrate to the desired CQC proved difficult. Multiple synthetic routes were investigated to convert the aryl fluorides to the sought after hydroxy groups. While some progress was made, the desired dihydroquinone product was difficult to purify and could not be oxidized to the desired quinone. This has led to the reevaluation of our synthetic route for these catalysts.


Open Access