In this critical review, the ring opening of non-activated 2-substituted aziridines via intermediate aziridinium salts will be dealt with. Emphasis will be put on the relationship between the observed regioselectivity and inherent structural features such as the nature of the C2 aziridine substituent and the nature of the electrophile and the nucleophile. This overview should allow chemists to gain insight into the factors governing the regioselectivity in aziridinium ring openings (81 references).
The ring opening of 2-alkyl-substituted 1,1-di(arylmethyl)-and 1-methyl-1-(1-phenylethyl)aziridinium salts by fluoride, chloride, bromide and iodide in acetonitrile has been evaluated for the first time in a systematic way, affording regioisomeric mixtures of primary and secondary fluorides, whereas the corresponding secondary β-chloro, β-bromo and β-iodo amines were obtained as the sole reaction products through regiospecific ring opening at the substituted position. Both experimental and computational results revealed a product stability-dictated reaction outcome through thermodynamic control in the chloride, bromide and iodide case, involving rearrangement of the initially formed primary halides to the more stable secondary halides. The ring opening of the same aziridinium salts by fluoride, however, was shown to be mediated by steric interactions (kinetic control), furnishing the corresponding primary β-fluoro amines as the main reaction products. Only for 2-acylaziridinium ions, the reaction outcome was shown to be under full substrate control, affording secondary β-fluoro, β-chloro, β-bromo and β-iodo amines through exclusive attack at the activated -carbonyl carbon atom.
New evidence questioning the multidimensionality of the aromaticity phenomenon exemplified in what is called orthogonality between the classical (structural and energetic) and magnetic aromaticity indices and measures is reported. For this purpose, the recently proposed methodologies for the quantitative characterization of the energy benefits associated with the cyclic arrangement of mobile π-electrons in polycyclic aromatic hydrocarbons are compared with the indices characterizing the extent of cyclic delocalization in the corresponding conjugated circuits. The reported close correlation between both types of indices implies that no discrepancies between classical and magnetic aromaticity measures exist provided the comparison is based on the indices of inherently local nature and/or the interfering contributions of contaminating conjugated circuits is properly taken into account in the description of aromaticity measures like topological resonance energy (TRE) or nucleus independent chemical shift (NICS).
The topological resonance energy (TRE) was conceived in the 1970s. From the very beginning, it was known that TRE is equal to the collective energy-effect of all cycles present in a conjugated molecule. Also in the 1970s a theory of cyclic conjugation was elaborated, by means of which it was possible to compute the energy-effect ef(Z) of each individual cycle Z present in a conjugated molecule. Yet, the connection between TRE and the ef(Z)-values was, until now, not studied. We now show that TRE and the sum of the ef(Z)-values are closely correlated but that a certain correction needs to be made by taking into account the energy-effects of pairs, triplets, quartets, etc. of cycles.
The synthetic utility of N-alkylidene-(2,3-dibromo-2-methylpropyl)amines and N-(2,3-dibromo-2-methylpropylidene)benzylamines was demonstrated by the unexpected synthesis of 3-methoxy-3-methylazetidines upon treatment with sodium borohydride in methanol under reflux through a rare aziridine to azetidine rearrangement. These findings stand in contrast to the known reactivity of the closely related N-alkylidene-(2,3-dibromopropyl)amines, which are easily converted into 2-(bromomethyl)aziridines under the same reaction conditions. A thorough insight into the reaction mechanism was provided by both experimental study and theoretical rationalization.
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