ChemInform Abstract: A Compilation and Analysis of Structural Data of Distorted Bridgehead Olefins and Amides

Abstract

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An efficient computational model to predict protonation at the amide nitrogen and reactivity along the C–N rotational pathway

“…In contrast, the pyramidalization at carbon remains relatively unchanged (χ C = 0.0-15.42°) with the carbonyl carbon essentially planar in the series, which is consistent with previous observations regarding amide bond distortion. 3,4 In agreement with the amide bond distortion parameters, the length of the N–C(O) bond varies between 1.474 Å and 1.365 Å, while the length of the C=O bond is between 1.201 Å and 1.233 Å.…”

“…1). 2 In contrast to planar amides, distorted amides have received much less attention 3 despite their profound implications for structure, 4 reactivity 5 and wide significance in biology and medicinal chemistry 6 (amide bond proteolysis, 6a isomerization of cis-trans peptides, 6b protein splicing, 6c β-lactam antibiotics, 6d conformational preferences of peptides, 6e generation of new pharmacophores and lead structures 6f ). More fundamentally, non-planar amides that are characterized by ground-state distortion provide crucial insight into the amide bond resonance, including the long-standing question of structural factors governing the O- vs. N-protonation switch.…”

Chemistry of Bridged Lactams and Related Heterocycles

“…Structural properties of non-planar olefins, including those in compounds 142 , have been recently reviewed. 56,104 …”

Chemistry of Bridged Lactams: Recent Developments

“…The redesign of the amide bond geometry through structural and electronic changes of substituents comprising the amide bond has had a profound impact on the physico-chemical properties of amides [3,4,5,6]. The alteration of the amide bond geometry generally leads to a reversal of traditional properties of amides, such as lower barrier to cis-trans rotation, increased length of the N-C(O) bond, favored protonation at the nitrogen atom, and increased reactivity in nucleophilic addition and hydrolysis [3,4,5,6].…”

“…The redesign of the amide bond geometry through structural and electronic changes of substituents comprising the amide bond has had a profound impact on the physico-chemical properties of amides [3,4,5,6]. The alteration of the amide bond geometry generally leads to a reversal of traditional properties of amides, such as lower barrier to cis-trans rotation, increased length of the N-C(O) bond, favored protonation at the nitrogen atom, and increased reactivity in nucleophilic addition and hydrolysis [3,4,5,6]. The geometric and structural changes of the amide bond are an established technique to affect properties of amide bonds in biology and medicinal chemistry [7,8,9,10], while recent advances in selective metal insertion into the amide bond driven by its distortion represent a thriving and general concept in organic synthesis [11,12].…”