Synthesis of valuable compounds through a cobalt-catalysed C-H functionalisation approach

CHIRILA, Paula Giorgiana (2021). Synthesis of valuable compounds through a cobalt-catalysed C-H functionalisation approach. Doctoral, Sheffield Hallam University.

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Directed C-H functionalisation protocols have attracted significant interest in recent years as they offer the possibility of forming new bonds selectively via C-H bond cleavage, without requiring pre-functionalised substrates whilst reducing waste production. Precious metals such as palladium and rhodium have been utilised to make considerable advancements in the field. However, recently there has been a shift towards the use of more environmentally friendly and cost-effective 3d-transition metals. High valent cobalt (Co)-catalysed C-H functionalisation has emerged as a tool for the development of a variety of protocols for the formation of novel C-C or C-heteroatom bonds. Of particular interest to this thesis is the formation of important C-N bonds using Co(III)-catalysed C-H amidation protocols. Furthermore, utilising the products of the C-H amidation reaction for synthesis of new nitrogen-based heterocycles is desirable due to their prevalence in biologically active compounds and agrochemicals. The focus of this thesis is developing efficient routes to valuable nitrogen containing heterocycles starting from a key Co(III)-catalysed C-H amidation step. In this context, the use of Cp*Co(III) catalysts for the amidation of benzamide and N-phenylisobutyramide type of substrates is reported using 1,4,2-dioxazol-5-ones as amidating agents. The isolable amidated products are thereafter converted to the valuable 1,2,3-benzotriazin-4(3H)-ones and N-acetylbenzotriazoles utilising tert-butyl nitrite (TBN) under mild conditions. Furthermore, another interest for this thesis is the development of Co(III)-catalysed C-H amidation protocols for more challenging alkenyl substrates. There is limited information about the mechanism by which these Co(III)-catalysed C-H amidation protocols proceed thus, DFT calculations and experimental mechanistic investigations are employed to elucidate the reaction mechanisms. Lastly, 1,2,3-benzotriazin-4-(3H)-ones are reacted with various coupling partners in an attempt to provide new synthetic starting points for preparation of other potentially valuable heterocyclic compounds via denitrogenation under low-valent metal catalysis. It was posible to develop facile one-pot routes towards the synthesis 1,2,3-benzotriazin-4(3H)-ones and N-acetylbenzotriazoles starting from readily available substrates, using Co(III)-catalysed C-H amidation reactions as initials steps. Expanding the scope to alkenyl substrates was more challenging due to limited availability of starting materials and the poor reactivity of the substrates with substituents at the -position. Finally, DFT studies have revealed that the migratory insertion step is most likely the rate limiting step for the Co(III)-catalysed C-H amidation reactions.

Item Type: Thesis (Doctoral)
Thesis advisor - Whiteoak, Christopher [0000-0003-1501-5582]
Thesis advisor - Hamilton, Alexander
Thesis advisor - Miller, Keith [0000-0001-8633-6952]
Additional Information: Director of studies: Dr. Christopher Whiteoak / Supervisors: Dr. Alexander Hamilton and Dr. Keith Miller.
Research Institute, Centre or Group - Does NOT include content added after October 2018: Sheffield Hallam Doctoral Theses
Identification Number:
Depositing User: Colin Knott
Date Deposited: 29 Oct 2021 14:31
Last Modified: 03 May 2023 02:08

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