Stereochemistry and chiroptical properties of 1,3-dialkylaziridinones (α-lactams). Chiral rules for the nonplanar amide chromophore

Abstract

Structural features, configurational stability, and chiroptical properties of the nonplanar amide group in α-lactams were investigated by means of ab initio (6-31 + G*) molecular orbital calculations on (1R)-aziridinone 1, (1R)-1-methylaziridinone 2, (1R,3R)-3-methylaziridinone 3, (1R,3R)-1,3-dimethylaziridinone 4a, its cis diastereomer (1S,3R)-1,3-dimethylaziridinone 4b, and (1R,3R)-3-tert-butyl-1-methylaziridinone 5, and by experimental CD spectra of 1-tert-butyl- and 1-(1′-adamantyl)-substituted 3(R)-3-tert-butylaziridinones 6 and 7. The nitrogen inversion barriers of 4a and 4b are 2.8 and 1.6 kcal mol−1, respectively. The lowest excited singlet state of all of the aziridinones is a valence state (the nO–πCO* transition); the second is a Rydberg state (the nN–3s transition). The signs of the first and second Cotton effects in the CD spectra of the compounds 6 and 7 coincide with the calculated ones for 1 and 2 and the trans isomers 3, 4a, and 5. According to the calculated and experimental data for aziridinones 1–7 as well as to the well-known data for other nonplanar amides, the sign of the first Cotton effects is determined by the intrinsic chirality of the nonplanar amide chromophore and obeys a spiral rule. For cases where the chromophore has the conformation around the N—C(O) bond, which is close to the antiperiplanar, a reverse octant rule is proposed.

Electronic Circular Dichroism of the Chiral Rigid Tricyclic Dilactam with Nonplanar Tertiary Amide Groups

“…The transitions 10−18 form a wide tail of dichroic absorption at its shorter wavelength side. The transitions 3 and 6 are nearly pure π−π* (∼90%) states, while the other ones are either nearly pure π−σ* (12) or exhibit significant proportions of n−π* configurations (8,9,10,15,16,18). This is particularly valid for the transitions 8, 15, and 16 for which the respective n−π* contributions (58, 70 and 75%) are even dominant.…”

“…Nonplanar amide deformations have been found in crystal structures of peptides/proteins, − natural products often of pharmacological significance (e.g., alkaloids, antibiotics) or polycyclic lactams. − The studies on various models (including the extreme case of 1-azabicyclo[2,2,2]octane-2-one − ) provided a finding that minor degree of amide nonplanarity is rather common and that it usually involves a partial sp 2 → sp 3 hybridization change (the pyramidalization) of the amide nitrogen atom, not only a simple rotation around the C′–N bond. Amide group in the nonplanar arrangement loses its symmetry plane ( C s ) and becomes an inherently chiral chromophore ( C 1 ) as has been shown first by us , and confirmed by others. ,− Therefore, it can be studied with advantage using chiroptical properties. Knowledge of the circular dichroism spectra of rigid nonplanar amides may provide valuable information on their role in other, more flexible systems, including a connection to biologically relevant peptides and proteins.…”

Syntone Chemistry. Theoretical study on the formation of glycine, alannine and serine

“…Aldimine, ketene, isocyanate acid, glycine are detected interstellar compounds [9][10][11][12][13][14][15][16][17][18]. Very interesting is that aziridinone was detected by mass spectrometry as a breakdown product of some oligopeptides [19]. Why not a…”

Syntone chemistry and prebiotic stage in life evolution 1. Aziridinone, a key compound in formation of the first proteinogenic amino acids and polypeptides

“…A careful analysis of the literature (Liebman & Greenberg 1974;Treschanke & Rademacher 1985;Greenberg et al 1991Greenberg et al , 1995Greenberg et al , 1996Shustov et al 1994;Harrison et al 2000;Goumans et al 2003;El Firdoussi et al 2004Tang et al 2004;Bach & Dmitrenko 2006;Kassaee et al 2008) concerning the structure of 2aziridinone reveals two somehow antagonistic aspects. Structural evaluations obtained through semiempirical mecano-quantic calculation identify as the most stable structure the planar one with the imine hydrogen H 5 in the plane of the α-lactam cycle ( Table 1).…”