%A Humair Omer
%T Exploring C?H Functionalization Reactions with Theory and Experiment
%X C?H bond functionalization reactions are powerful, efficient, and potentially step-economic strategy for the construction of carbon?carbon and carbon?heteroatom bonds in organic synthesis. In recent years, novel Ni-catalyzed C?H bond functionalization reactions using N,N bidentate directing groups have been developed to selectively activate inert C?H bonds. However, the reaction mechanisms and origins of reactivity and selectivity of many of these organic transformations remain unclear. A detailed understanding of the molecular processes involved is essential for understanding and developing more efficient and diverse C?H functionalization reactions. Density functional theory (DFT) has emerged as a powerful tool to elucidate reaction mechanisms and intricate details of the elementary steps involved, and divergent reaction pathways in transition metal-catalyzed reactions. In this dissertation, the mechanisms of Ni-catalyzed C?H oxidative annulation, arylation, alkylation, benzylation and sulfenylation with N,N-bidentate directing groups are investigated using DFT calculations. 

Ni-catalyzed C?H functionalization reactions can be broadly divided into two distinct mechanistic steps: (i) C?H metalation (ii) C?C or C?heteroatom bond formation steps. Specifically, the C?H metalation may occur via either the concerted metalation-deprotonation (CMD) or ?-complex-assisted metathesis (?-CAM) mechanism. The subsequent C?C and C?heteroatom bond formation steps may occur via closed-shell Ni(II) or Ni(IV) intermediates. Alternatively, radical pathways involving Ni(III) complexes are also possible. Our studies indicated that the reaction mechanism of Ni-catalyzed C?H functionalization is substrate-dependent. The mechanistic insights gained from the computational studies were employed to investigate a number of experimental phenomena including substituent effects on reactivity, chemo- and regioselectivity, ligand and directing group effects, and the effects of oxidants. 

Furthermore, a novel C(sp3)?H functionalization methodology was developed to synthesize biologically relevant vinyl sulfone-containing compounds of pharmacologically prevalent picolyl amides with allenic sulfones. The reaction conditions are mild. The starting materials can be prepared from readily available sources. The reaction has a broad functional group tolerance. Mechanistic studies suggested that the reaction likely operates via a rare pyridine-initiated and p-toluenesulfinate anion-mediated activation analogous to phosphine-triggered reactions and Padwa?s allenic sulfone chemistry.
%D 2020
%K C-H functionalization, Nickel catalysis, vinyl sulfones, allenyl sulfones, reaction mechanism, pyridine-intiated
%I University of Pittsburgh
%L pittir38137