title: Structures of Highly Twisted Amides Relevant to Amide N-C Cross-Coupling: Evidence for Ground-State Amide Destabilization.
abstract: 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 (15) N 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.
authors: Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna, 1090, Austria.
authors: Vittorio
authors: V
authors: Pace
authors: Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna, 1090, Austria.
authors: Wolfgang
authors: W
authors: Holzer
authors: Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, United States.
authors: Guangrong
authors: G
authors: Meng
authors: Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, United States.
authors: Shicheng
authors: S
authors: Shi
authors: Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, United States.
authors: Roger
authors: R
authors: Lalancette
authors: Department of Chemistry, Wroclaw University, F. Joliot-Curie 14, Wroclaw, 50-383, Poland.
authors: Roman
authors: R
authors: Szostak
authors: Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, United States. michal.szostak@rutgers.edu.
authors: Michal
authors: http://orcid.org/0000-0002-9650-9690
authors: M
authors: Szostak
keywords: N−C activation; amides; rotation; steric hindrance; twisted amides