Charge-Transfer Complexes for Amine Synthesis

A method to generate α-amino radicals, via a photoinduced charge-transfer complex, is reported. A multicomponent radical fragmentation-cyclization reaction was developed, combining secondary amines, cyclopropyl carboxaldehydes and alkenes, to generate cyclopentyl methylamines. To initiate the fragmentation step, single-electron reduction of alkyliminium ions to α-amino radicals was achieved, using an aromatic thiol and visible light irradiation. Mechanistic and computational studies supported the formation of a transient, ion-pair charge-transfer complex between iminium and thiolate ions. DFT calculations indicated that irradiation of the complex with visible light could promote intra-complex electron transfer from the thiolate HOMO to the iminium LUMO. This method of α-amino radical formation was extended to acyclic aldehydes, by development of a radical reductive amination, using thiol as the single-electron reductant and hydrogen atom source. Subsequently, the chemoselective reductive amination of secondary amines over primary amines was attempted. Preliminary studies on a di-amine drug indicated that the radical reductive amination had high selectivity for primary aminothiazoles over secondary amines, contrasting with existing polar reductive amination techniques.

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2020

Author dc:creator

• Kohara, Keishi

Advisor dc:contributor.advisor

• Gaunt, Matthew

• Organic Chemistry
• Synthetic Methodology
• Photochemistry
• Charge-Transfer Complexes
• Radical Chemistry

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/36f0af7a-ee43-4512-986f-cf006ab351dd/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.64486

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/317373