Development of Earth Abundant Metal-Catalyzed Reactions to Construct Heterocycles

N-Heterocyclic scaffolds are ubiquitous in natural and pharmaceutical compounds, and their significance has driven extensive efforts toward developing efficient synthetic methods. Our group focused on efficiently triggering C–N bond formation via different reactive nitroso intermediates. My research has been centered on the development of new methods to (a) construct sp3-C–Nar bonds from nitroarene and (b) explore the generality of the deoxygenation to convert 1,2-oxazines into pyrroles. The exposure of ortho-substituted nitroarenes to 3 mol % of (4,7-MeO-phen)Fe(OAc)2 and phenylsilane as the stoichiometricreductant afforded six-or seven-membered N-heterocycles. The scope of the reaction is broad and tolerates a range of electron-releasing or electron withdrawing substituents on the nitroarene, and the ortho-substituent can be modified to construct benzoxazines, dihydro benzothiazines, tetrahydroquinolines, tetrahydroquinoxalines, or tetrahydrobenzo-oxazepines. A tandem cycloaddition/iron-catalyzed oxygen- atom deletion reaction was developed to efficiently construct N-arylpyrroles. Kinetic studies revealed a first-order rate dependence in catalyst, oxazine, and silane concentrations, and an inverse kinetic order in acetate was observed. Kinetic isotope effect measurements, and Eyring analysis provided mechanistic insight to suggest that N–O bond cleavage of the oxazine intermediate is turnover-limiting and occurs via a highly ordered σ-bond metathesis transition state. Lastly, I discovered a new method to access medium-sized rings via carbene intermediates from N-tosylhydrazones.

Author dc:creator

• Thi Hong Van Vu (23292142)

• Chemistry
• Organic

Statement dc:rights

• In Copyright
• Open Access after 2028-01-01

DOI dc:identifier

https://doi.org/10.25417/uic.31451893.v1

OAI identifier oai:identifier

oai:figshare.com:article/31451893