Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Exploring C−H Functionalization Reactions with Theory and Experiment

Omer, Humair (2020) Exploring C−H Functionalization Reactions with Theory and Experiment. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Download (29MB) | Preview


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 σ-complex-assisted metathesis (σ-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.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Omer, Humairhbo4@pitt.eduhbo40000-0002-5245-6048
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee CoChairBrummond,
Committee CoChairLiu,
Committee MemberFloreancig,
Committee MemberJordan,
Committee MemberNoonan,
Date: 8 June 2020
Date Type: Publication
Defense Date: 27 January 2020
Approval Date: 8 June 2020
Submission Date: 14 January 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 351
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: C-H functionalization, Nickel catalysis, vinyl sulfones, allenyl sulfones, reaction mechanism, pyridine-intiated
Date Deposited: 08 Jun 2020 16:52
Last Modified: 08 Jun 2020 16:52


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item