Radical-radical cyclization cascades of barbiturates triggered by electron-transfer reduction of amide-type carbonyls

Huanming Huang, David Procter

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    Abstract

    Radical–radical cyclization cascades, triggered by single-electron transfer to amide-type carbonyls by SmI2–H2O, convert simple achiral barbiturates in one step to hemiaminal- or enamine-containing tricyclic scaffolds containing up to five contiguous stereocenters (including quaternary stereocenters). Furthermore, we describe the surprising beneficial effect of LiBr on the most challenging of the radical–radical cyclization cascades. An alternative fragmentation–radical cyclization sequence of related substrates allows access to bicyclic uracil derivatives. The radical–radical cyclization process constitutes the first example of a radical cascade involving ET reduction of the amide carbonyl. Products of the cascade can be readily manipulated to give highly unusual and medicinally relevant bi- and tricyclic barbiturates.
    Original languageEnglish
    JournalJournal of the American Chemical Society
    Volume138
    Issue number24
    Early online date31 May 2016
    DOIs
    Publication statusPublished - 2016

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