Structures of Highly Twisted Amides Relevant to Amide N−C Cross-Coupling: Evidence for Ground-State Amide Destabilization

Vittorio Pace, Wolfgang Holzer, Guangrong Meng, Shicheng Shi, Roger Lalancette, Roman Szostak, Michal Szostak (Korresp. Autor*in)

    Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed


    Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N−C activation/cross-coupling reactions are highly twisted around the N−C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The 15N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N−C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds.
    Seiten (von - bis)14494-14498
    FachzeitschriftChemistry: A European Journal
    PublikationsstatusVeröffentlicht - 4 Okt. 2016

    ÖFOS 2012

    • 104015 Organische Chemie
    • 104026 Spektroskopie
    • 104022 Theoretische Chemie