Abstract
Density functional theory calculations with the B3LYP functional were performed for the title ring‐opening reaction to understand the intrinsic activating and directing effects of the N‐substituents, as well as the electron donating effect of the para‐substituted (Y = Cl, H, Me) phenyl group at the more hindered benzylic C2 atom. The N‐tosyl group (i.e., N‐Tos) or the N‐(2‐pyridyl)sulfonyl group (i.e., N‐Py) was introduced to activate the ring nitrogen atom (N1) and the para‐substituted (Y = Cl, H, Me) phenyl group for the activation of the C2 atom. Conformational searches and geometry optimizations were performed for the N‐(para‐substituted)phenylaziridines (1∼6). Calculations indicate that the aziridine 6 (i.e., Py/Me) has the most elongated C2N1 bond intrinsically due to the electronic activating effects, implying the aziridine 6 to be the most potent candidate for the more‐hindered C2 opening. Transition states (TSs) were investigated for the prospective ring‐opening paths (I∼IV), considering the types of intermolecular push–pull interactions between the N‐activated phenylaziridines and the cuprate. The N‐Py group provides an unique C2‐favored TS along the path IV, which the N‐Tos group cannot afford, due to the less charge transfer from the nucleophilic CH of the cuprate into the electrophilic C2 atom. Furthermore, the e‐donating effect of the para‐substituents (Y = Cl, H, Me) enhances the C2 opening for the path IV. This study enables us to understand the unusual ring‐opening phenomena in terms of electronic and directing effects and hence may serve as a tool to design substrates for highly regioselective ring openings. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011