Rational Design of Fluoroalkylated Transition Metal Complexes for Fluoroalkylation Reactions

@mastersthesis{xue2023,
  title = {Rational Design of Fluoroalkylated Transition Metal Complexes for Fluoroalkylation Reactions},
  author = {Xue, Teng},
  year = {2023},
  month = may,
  publisher = {Lehigh University},
  keywords = {catalysis, Cobalt, fluoroalkylation, Nickel, Organometallic},
  abstract = {There is a continuous demand to develop better ways to incorporate fluoroalkyl groups into organic molecules, as such functionalities are known to facilitate the stability, reactivity, and conformational bias of their parent molecule. The interest in fluoroalkylation chemistry has created a need for better synthetic methodologies to access fluoroalkylated transition metal complexes. In comparison with second- and third-row transition metals, first-row transition metals are more desirable catalysts due to their lower cost and higher natural abundance.The first part of this dissertation briefly describes the synthesis of various perfluoroethylated nickel(II) complexes ([LnNi(CF2CF3)2], L = MeCN, bipyridine, pyridine) and their use in catalytic pentafluoroethylation of (hetero)arenes. Additionally, we describe the design of a partially fluorinated trifluoroethylated nickel(II) precatalyst ([(bipyridine)Ni(CH2CF3)2]) for Suzuki-type trifluoroethylation reactions between (hetero)arylboronic acids and a variety of alkyl halides.While routes to fluoroalkylated nickel complexes have been well-developed, the preparation of related cobalt complexes remains challenging and limited. To fill a void in this knowledge, the second part of this dissertation describes simple synthetic routes to afford a family of perfluoroalkylated cobalt(III) complexes ([Co-Rf], Rf = CF3, C2F5, n- C3F7, C4F8). Electrochemical analyses reveal that [(MeCN)4Co(C2F5)2][PF6] is more easily reduced compared to [(MeCN)3Co(C2F5)3], which has implications for the development of redox-triggered reactions involving the intermediacy of cobalt(II). Notably, a variety of well-defined perfluorometallacyclopentane complexes of cobalt ([Co(C4F8)]) have alsobeen synthesized and fully characterized for the first time. Access to these perfluoroalkylated cobalt complexes provides a foundation to explore less expensive and more diverse approaches to potential fluoroalkylation reactions.Lastly, the efforts to an optimized synthesis of the artificial nucleoside bearing the 5-(pyrimidin-2-yl)-pyrrolo[3,2-b]pyridine (PPP) motif are detailed in this dissertation. Our preliminary findings provide a foundation to further coordinate this unique chelating ligand with different transition metals within duplex DNA. The resulting metal-chelating artificial nucleoside is proposed to more closely resembled naturally occurring DNA base pairs whose function is not to support an internal metal-mediated base pair but rather to coordinate metals for labeling purposes and/or to perform bio-orthogonal reaction chemistries in the chiral environment of the major groove of duplex DNA.},
}