Distortion of the amide bond in amides and lactams. Photoelectron-spectrum and electronic structure of 3,5,7-trimethyl-1-azaadamantan-2-one, the most twisted amide

Kirby, Anthony J.; Komarov, Igor V.; Kowski, Klaus; Rademacher, Paul

doi:10.1039/a902321f

Cited by 38 publications

(23 citation statements)

References 18 publications

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“…From a qualitative standpoint, these semilocalized orbitals are significantly mixed and energetically split by a complex balance of conjugative and inductive effects, and through-bond and through-space interactions. (See, e.g., the detailed analysis by Kirby et al [64] on this interaction in the N-C@O unit of a representative system, 1-aza-adamantan-2-one. )…”

Section: Ionization Energiesmentioning

confidence: 96%

On the molecular and electronic structure of matrine-type alkaloids

et al. 2006

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Section: Ionization Energiesmentioning

confidence: 96%

On the molecular and electronic structure of matrine-type alkaloids

et al. 2006

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“…Clearly, rotation without pyramidalisation is energetically unfavourable and many examples of twisted amides are testament to this. The shift to sp 3 hybridisation at the amidic nitrogen is clearly demonstrated when twisting of the N–C(O) bond is geometrically enforced by tricyclic and bicyclic bridged lactams [7,8,9,10,11,12,13]. Kirby’s “most twisted amide” 1-aza-2-adamantanone, synthesised in 1998 [10,12], and Tani and Stoltz’s 2-quinuclidone, synthesised in 2006 [14], exemplify the fully twisted amide, geometrically and chemically.…”

Section: Introductionmentioning

confidence: 99%

Heteroatom Substitution at Amide Nitrogen—Resonance Reduction and HERON Reactions of Anomeric Amides

Glover

Rosser

2018

Molecules

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This review describes how resonance in amides is greatly affected upon substitution at nitrogen by two electronegative atoms. Nitrogen becomes strongly pyramidal and resonance stabilisation, evaluated computationally, can be reduced to as little as 50% that of N,N-dimethylacetamide. However, this occurs without significant twisting about the amide bond, which is borne out both experimentally and theoretically. In certain configurations, reduced resonance and pronounced anomeric effects between heteroatom substituents are instrumental in driving the HERON (Heteroatom Rearrangement On Nitrogen) reaction, in which the more electronegative atom migrates from nitrogen to the carbonyl carbon in concert with heterolysis of the amide bond, to generate acyl derivatives and heteroatom-substituted nitrenes. In other cases the anomeric effect facilitates SN1 and SN2 reactivity at the amide nitrogen.

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“…7,8 Though much rarer than standard amides, such species are important because they are encountered during cis–trans isomerization processes essential to protein folding, 9–11 have been proposed as intermediates in amide bond cleavage 12–14 , and are required to experimentally examine the effect of bond rotation on any type of amide reactivity such as protonation 15–17 or other reactions. 8,18–20 …”

Section: Introductionmentioning

confidence: 99%

Stability of Medium-Bridged Twisted Amides in Aqueous Solutions

2009

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“Twisted” amides containing non-standard dihedral angles are typically hypersensitive to hydrolysis, a feature that has stringently limited their utility in water. We have synthesized a series of bridged lactams that contain a twisted amide linkage but which exhibit enhanced stability in aqueous environments. Many of these compounds were extracted unchanged from aqueous mixtures ranging from the strongly basic to the strongly acidic. NMR experiments showed that tricyclic lactams undergo reversible hydrolysis at extreme pH ranges, but that a number of compounds in this structure class are indefinitely stable under physiologically relevant pH conditions; one bicyclic example was additionally water-soluble. We examined the effect of structure on the reversibility of amide bond hydrolysis, which we attributed to the transannular nature of the amino acid analogs. These data suggest that medium-bridged lactams of these types should provide useful platforms for studying the behavior of twisted amides in aqueous systems.

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Distortion of the amide bond in amides and lactams. Photoelectron-spectrum and electronic structure of 3,5,7-trimethyl-1-azaadamantan-2-one, the most twisted amide

Cited by 38 publications

References 18 publications

On the molecular and electronic structure of matrine-type alkaloids

On the molecular and electronic structure of matrine-type alkaloids

Heteroatom Substitution at Amide Nitrogen—Resonance Reduction and HERON Reactions of Anomeric Amides

Stability of Medium-Bridged Twisted Amides in Aqueous Solutions

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