Nickel-catalyzed reactions of nontraditional electrophiles to set stereogenic centers

Shacklady McAtee, Danielle Maria
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University of Delaware
This dissertation focuses on investigations of nickel-catalyzed reactions of nontraditional electrophiles to set stereogenic centers. Chapter 1 describes a novel nickel(0)-catalyzed cyclization of N -benzoylaminals for isoindolinone synthesis. This method enables preparation of a variety of isoindolinones with substitution on the benzoyl fragment and C-3 carbon. This reaction likely proceeds via an α-amidoalkylnickel(II) intermediate, which then may cyclize via either an electrophilic aromatic substitution or an insertion pathway. Chapter 2 describes the development of a nickel-catalyzed cross coupling of benzylic ammonium triflates with aryl boronic acids to afford diarylmethanes and diarylethanes. This reaction proceeds under mild reaction conditions and with exceptional functional group tolerance. Further, it transforms branched benzylic ammonium salts to diarylethanes with excellent chirality transfer. A second-generation catalyst system is also discussed for the activation of benzylic ammonium triflates. This method relies on the use of Ni(cod) 2 without ancillary phosphine or N -heterocyclic carbene ligands as catalyst. Preliminary mechanistic studies have been undertaken to probe the identity of the active catalyst for the second-generation phosphine-less catalyst system for both the napthyl and phenyl substituted ammonium salts. Chapter 3 focuses on the progress towards activating the C-N bond of amino acids. Preliminary results have been obtained for activating the C-N bond of β-amino acids, which represents the first example of non-benzylic C-N activation for our group. Synthesis of a new model substrate that includes a chelating group to help aid in the activation of the C-N bond of α-amino acids is also discussed.