The Cyclopropane Ring as a Reporter of Radical Leaving-Group Reactivity for Ni-Catalyzed C(sp3)–O Arylation

The ability to understand and predict reactivity is essential for the development of new reactions. In the context of Ni-catalyzed C­(sp3)–O functionalization, we have developed a unique strategy employing activated cyclopropanols to aid the design and optimization of a redox-active leaving group fo...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of the American Chemical Society 2020-07, Vol.142 (30), p.13246-13254
Hauptverfasser: Mills, L. Reginald, Monteith, John J, dos Passos Gomes, Gabriel, Aspuru-Guzik, Alán, Rousseaux, Sophie A. L
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The ability to understand and predict reactivity is essential for the development of new reactions. In the context of Ni-catalyzed C­(sp3)–O functionalization, we have developed a unique strategy employing activated cyclopropanols to aid the design and optimization of a redox-active leaving group for C­(sp3)–O arylation. In this chemistry, the cyclopropane ring acts as a reporter of leaving-group reactivity, since the ring-opened product is obtained under polar (2e) conditions, and the ring-closed product is obtained under radical (1e) conditions. Mechanistic studies demonstrate that the optimal leaving group is redox-active and are consistent with a Ni­(I)/Ni­(III) catalytic cycle. The optimized reaction conditions are also used to synthesize a number of arylcyclopropanes, which are valuable pharmaceutical motifs.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.0c06904