Oxidative carbon-carbon bond formation

Thesis

Oxidative bond formation is a powerful technique for the efficient and atom-economic construction of carbon-carbon bonds. This thesis explores two systems that harness this reactivity to generate densely functionalised products. Initially, we describe an oxidative allylation discovered during a visible light eliminative photocyclisation. Investigation into the reaction mechanism determined that the cyclisation and oxidative allylation are two independent steps. However, the reaction is extremely substrate and nucleophile dependant, with limited tolerance for modification.

The expansion of an oxidative cross-coupling between C-2 substituted indoles and 2-naphthols developed by the group is described, in which the synthesis of atropisomeric heterobiaryls had been achieved chemo- and enantioselectively with the use of a FeCl3/PyBOX ligand system. The reaction mechanism is determined: single electron oxidation of the naphtholic partner to the Fe(III)-bound naphthoxy radical. This is followed by a nucleophilic attack by the indole, geometrically controlled by the asymmetric environment created by the ligand. During this investigation, the off-cycle oxidation of an indole to the radical cation and its cyclisation to an unexpected 6,5,6-tricyclic chlorinated product is observed. Modification of the substitution pattern of the indolic partner in the cross-coupling allows for the synthesis of cyclised naphthofuro[2,3-b]indolines via the same methodology. This is achieved in a racemic fashion for a selection of 2-naphthols and 3- and 2,3-substituted indoles. Reintroduction of the PyBOX ligand leads to the successful induction of enantioselectivity into the coupling, producing the products in up to 77% yield and 92:8 e.r.

Authors: Keenlyside, M

• DOI: 10.5287/ora-j5ozawgyd
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: oxidative bond formation; iron catalysis; naphthofuroindoline synthesis; visible light photochemistry
• Subjects: Organic photochemistry; Enantioselective catalysis