Radical Cyclisation Cascades Triggered by Electron-Transfer to Amide Derivatives

Abstract

Radical cyclisation and cyclisation cascades are a powerful synthetic approach for the formation of multiple carbon-carbon bonds to generate complex carbo and heterocyclic architectures in synthetic chemistry. Radical cyclisation and cyclisation cascades triggered by electron transfer reduction to amide-type carbonyls have been demonstrated for the first time. In one step, simple achiral barbiturates can be converted to hemiaminal or enamine-containing tricyclic scaffolds or unprecedented spirotetracyclic architectures containing up to five contiguous stereocentres (including quaternary stereocentres) with high diastereocontrol. Electron transfer reduction to amide-type carbonyls triggers radical heterocyclisation and heterocyclisation cascades that deliver complex cyclic compounds containing bridgehead nitrogen atoms with up to five contiguous stereocentres with complete diastereocontrol. We have also demonstrated the first example of radical cyclisation triggered by reductive electron transfer to urea carbonyls. A variety of bicyclic products could be constructed in good to excellent yields with complete diastereocontrol. Furthermore, the radical cyclisation of urea carbonyls could be exploited in radical cyclisation cascades. The cyclisation cascades involve the generation of unusual radical anions from urea carbonyls followed by the trapping of aminal radical intermediates.

Date of Award	31 Dec 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Sabine Flitsch (Supervisor) & David Procter (Supervisor)