Regioselective carbon-nitrogen bond formation via oxidative transition metal catalysis

Louis Marchetti, University of Rhode Island


The synthesis of carbon-nitrogen (C-N) bonds is an area of research that has garnered significant interest due to the ubiquity of C-N bonds in pharmaceuticals and natural products. Various methods exist for forming C-N bonds, most recognizably Buchwald-Hartwig amination, but these reactions typically require functionalization of either the C-H or N-H bond resulting in the formation of harmful byproducts. As a result, the need to explore alternative means for synthesizing C-N bonds merits consideration. An alternative means for achieving C-N bond formation lies in the oxidative cross coupling of carbon-hydrogen (C-H) and nitrogen-hydrogen (N-H) bonds. While this approach eliminates the necessity for the prefunctionalization of C-H and N-H bonds, reactions employing oxidative cross coupling can be plagued with poor regioselectivity. As a result, the use of directing groups and transition metal catalysis is typically employed to circumvent this issue. ^ The primary focus of this dissertation is the discussion of newly developed methodologies that enhance the regioselective control of oxidative C-N bond formation. In each instance hypervalent iodine is used in conjunction with a transition metal catalyst to help govern the site of amination on various electron-rich, and moderately deactivated, arene systems. ^ The first manuscript entitled "Regioselective Gold Catalyzed Oxidative C-N Bond Formation" discusses the effects of a gold (I) catalyst when oxidatively coupling phthalimide to simple arenes in the presence of hypervalent iodine. Mechanistic insight suggests a pathway consistent with that of electrophilic aromatic substitution with a preference to impart para selectivity. This manuscript has been published as a communication in Organic Letters. ^ The second manuscript entitled "Regioselective C—N Bond Formation by Aminoiodanes" employs a copper (II) reagent for an economical means of aminating various 2-phenylpyridine derivatives. The manuscript detailing this work has been published in Chemical Communications. ^ The third manuscript entitled "Efforts Towards the Synthesis of a Molecular Probe targeting the D2 Receptor" deviates from C-N bond formation and focuses on the synthetic methodology employed for the probe's construction. Upon the completion of the synthesis this work will be submitted for publication to the Journal of Organic and Biomolecular Chemistry. ^ The final manuscript entitled "Solution-Phase Synthesis of Dipeptides: A Capstone Project that Employs Key Techniques in an Organic Laboratory Course" is an original laboratory experiment designed to serve as a final assessment of the skills acquired throughout the sophomore level organic chemistry laboratory course. This work has been accepted in the Journal of Chemical Education. ^

Subject Area

Chemistry, Organic

Recommended Citation

Louis Marchetti, "Regioselective carbon-nitrogen bond formation via oxidative transition metal catalysis" (2015). Dissertations and Master's Theses (Campus Access). Paper AAI3688822.