Barriers to Rotation in ortho-Substituted Tertiary Aromatic Amides: Effect of Chloro-Substitution on Resonance and Distortion

Abstract

Planarity of the amide bond represents one of the most widely recognized properties of amides. Herein, we report a combined structural and computational study on the effect of ortho-substitution on resonance and barriers to rotation in tertiary aromatic amides. We demonstrate that ortho-chloro substitution in a class of benzamides that are important from the reactivity and medicinal chemistry perspective results in increased barriers to rotation around both the N-C(O) and C-C(O) axes. The effect of steric hindrance on structures, resonance energies, barriers to rotation, and proton affinities is discussed. The present study strongly supports the use of ortho-substitution in common benzamides to strengthen amidic resonance.

Amide Effects in C−H Activation: Noncovalent Interactions with L‐Shaped Ligand for meta Borylation of Aromatic Amides

“…Interestingly,inall cases of ortho-monosubstituted substrates (5a-g), high levels of meta selectivity were observed, except for the amide 5c,w hich afforded lower meta selectivity resulting from the rotational barrier. [22] Notably, 5e and 5h,h aving as cope of multiple borylations,selectively underwent meta borylation under the developed reaction conditions.I nc ase of various disubstituted amides (5i-l), excellent meta selectivity was observed. Moreover, para-substituted amides (5m-p)exhibited remarkable meta selectivity as well, except for the amide 5o,w hich suffered from poor conversion and afforded nearly 54 % meta borylation.…”

“…Remarkably,switching the alkyl groups from Me 2 to Et 2 ! [22] Notably, 5e and 5h,h aving as cope of multiple borylations,selectively underwent meta borylation under the developed reaction conditions.I nc ase of various disubstituted amides (5i-l), excellent meta selectivity was observed. i Pr 2 !…”

Computational Study of Mechanism and Thermodynamics of Ni/IPr-Catalyzed Amidation of Esters

“…Amide C–N bond activation and functionalization provide a powerful strategy to utilize amide as a central synthon [ 1 , 2 , 3 , 4 , 5 , 6 ]. Despite the remarkable value of this strategy, the development of amide C–N bond activation has progressed slowly due to the resonance nature of amide and the resulting difficulty for bond dissociation [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Recently, Garg and coworkers discovered the outstanding performance of nickel catalysis for amide C–N bond activation [ 17 ], leading to the development of a series of exciting Ni-catalyzed cross coupling reactions [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”

Amide Effects in C−H Activation: Noncovalent Interactions with L‐Shaped Ligand for meta Borylation of Aromatic Amides

“…We chose N , N ‐diisopropyl‐bearing amides instead of a butyl group because of the higher product conversion. Interestingly, in all cases of ortho ‐monosubstituted substrates ( 5 a – g ), high levels of meta selectivity were observed, except for the amide 5 c , which afforded lower meta selectivity resulting from the rotational barrier . Notably, 5 e and 5 h , having a scope of multiple borylations, selectively underwent meta borylation under the developed reaction conditions.…”