Visible-light photoredox-catalysed radical cascade reactions

Li, Sifan (2023). Visible-light photoredox-catalysed radical cascade reactions. University of Birmingham. Ph.D.

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Abstract

The research presented in this thesis details several novel radical cascade transformations under copper-catalysis or visible-light photoredox-catalysis.

The synthesis of [1,2]-annulated indoles from ene-ynamides via a radical triggered fragmentary cyclisation cascade under copper-catalysis or photoredox-catalysis is described. This reaction proceeds through a radical addition, radical cyclisation, desulfonylative aryl migration, and site-selective C(\(sp^2\))-N cyclisation sequence. This work presents an example of a radical Smiles rearrangement process followed by aza-Nazarov type cyclisation, which enables the selective incorporation of the electron-rich aryl ring into the indole motif regardless of its original position.

The second part of thesis explores the synthesis of α-arylated carboxylic acids, esters, and amides from consecutive defluorination of α-trifluoromethyl alkenes in the presence of potassium alkyltrifluoroborates, water, and nitrogen/oxygen nucleophiles under organophotoredox-catalysed conditions. The utility of this method has been expanded through several product transformations. Mechanistic studies show that this metal-free reaction consists of a defluorinative alkylation, defluorinative hydroxylation, and defluorinative amination/hydroxylation cascade.

Finally, the modular synthesis of α-tertiary primary amines using α-aryl vinyl azides, redox-active N-(hydroxy)phthalimide ester, and cyanoarenes under visible-light conditions is described. This strategy shows excellent functional group compatibility and allows the straightforward synthesis of 2,2-diaryl tetrahydroquinolines and 1,2-amino alcohols. The mechanistic studies support two parallel reductive photocatalytic cycles allowing for the denitrogenative alkylarylation of vinyl azides through decarboxylative radical addition followed by hetero-radical cross-coupling between α-amino alkyl radicals and aryl radical anions.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):