Nucleophilic Catalysis of Amide Isomerization

The Reactivity ofN-Coordinated Amides in Metallopeptide Frameworks: Molecular Events in Metal-Induced Pathogenic Pathways?

“…At 25 °C, the free activation enthalpies Δ G # of cis – trans isomerization are 17.8 kcal mol −1 for 1 and 13.4 kcal mol −1 for 5 . When compared with literature data for other activated amide isomerization reactions, such as nucleophilic33 or intramolecular34 catalysis, a ΔΔ G # value of −4.4 kcal mol −1 indicates a very efficient lowering of the activation barrier. The rate enhancement at room temperature is approximately 1000‐fold.…”

Cis−Trans Isomerization of Organic Molecules and Biomolecules: Implications and Applications

“…For example, the E-population is doubled when R′ is changed from an ethyl group ([E] ) 16.8%) to a vinyl group ([E] ) 32.7%). 357 Intra- [395][396][397][398] and intermolecular 378,379,399 hydrogen bonding may also perturb the cis-trans equilibrium of amides and the syn-anti isomer equilibrium of carbamates. As an example, pentafluorophenyl-lone pair interaction is sufficiently strong to shift the cis:trans ratio of secondary amides: the cis-isomer is entropically favored, suggesting that the pentafluorophenyl group acts as a Lewis acid.…”

Selective Reduction of Barbituric Acids Using SmI2/H2O: Synthesis, Reactivity, and Structural Analysis of Tetrahedral Adducts

“…Interestingly, the barbiturate monoreduction products would formally constitute a new class of tetrahedral intermediates of amide bond addition reactions, only few of which have been successfully isolated to date because of their transient nature. [5] Single-electron-transfer reactions open up unexplored reaction space charted with chemoselectivity and reactivity levels difficult to access by ionic reaction mechanisms. [6] The generation of ketyl-type radicals with SmI 2 is particularly valuable in this regard because of the excellent chemoselectivity imparted by the reagent and the potential to effect polarity reversal of the carbonyl group through a singleelectron-reduction event (Figure 1 b).…”

“…[7,8] The hemiaminal products are analogous to tetrahedral intermediates derived from amide addition reactions. [5] Moreover, the radical intermediates formed by the one-electron reduction have been utilized in intramolecular additions to alkenes. For the first time in any SmI 2 -mediated cross-couplings of acyl-type radicals, [11] these additions proceed with full control of diastereoselectivity.…”