Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)

Graduate Group


First Advisor

Gary A. Molander


The synthesis of alpha-aryl, -alkenyl, and -alkynyl esters and amides has been extensively investigated over the past decade because of the prevalence of these substructures within the cores of molecules of biological instance, namely non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. New methods were developed that employ potassium organotrifluoroborate salts to overcome the drawbacks of previously reported approaches, such as lack of functional group compatibility and the necessity for an organometallic species that must be formed under low temperature, inert conditions. Optimization was carried out to determine ideal catalysts, ligands, bases, and solvents for each of the desired transformations, leading to the development of conditions for the cross-coupling of 2-chloroacetates and 2-chloroacetamides with aryl-, heteroaryl-, alkenyl-, and alkynyltrifluoroborates. The developed methods boast enhanced functional group compatibility and expand the scope of the electrophilic components compared to previous protocols.

Significant interest has recently emerged in the synthesis of sp2-sp3 bonds involving non-aromatic heterocyclic structures. Interestingly, while sp2-sp3 coupling methods are known, many of the existing protocols are either completely ineffective or extremely low-yielding for secondary alkyl substrates containing heteroatoms. Conditions were developed that allowed a variety of substituted aryl and heteroaryl bromides to be cross-coupled reductively with piperidinyl, tetrahydropyranyl, pyrrolidinyl, tetrahydrofuranyl, azetidinyl, and oxetanyl bromides. The developed method utilizes bench-stable components under conditions that are tolerant of numerous functional groups, which is compatible with late-stage incorporation of saturated heterocyclic structures into larger molecules of interest. The reductive protocol was expanded to allow alkyl tosylates of nonaromatic heterocyclic systems to participate as coupling partners with aryl and heteroaryl bromides. This development allows the use of bench stable, crystalline solids that can be prepared from inexpensive, commercially available alcohols.

2,1-Borazaronaphthalenes have received a significant amount of attention because of their potentially impactful properties in the fields of pharmaceuticals and materials science. Based on conditions established for the reductive coupling of non-aromatic heterocyclic bromides with aryl bromides, the cross-coupling of non-aromatic heterocyclic halides with 2,1-borazaronaphthalenes was explored. Conditions were developed that allow reductive cross-coupling of alkyl iodides with a variety of 3- bromo-2,1-borazaronaphthalenes. This method provides a valuable, direct route to alkylated, functionalized azaborine systems.

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