To What Extent Can Nine‐Membered Monocycles Be Aromatic?

Abstract

Ab initio and density functional computations have been used to characterize the heteronins. New targets for synthesis are suggested on the basis of the results. The aromaticity of the heteronins was evaluated via numerous criteria such as magnetic properties (NICS and δH), geometric indices (Bird, BDSHRT and HOMA), aromatic stabilization energies (ASE), and the barriers to planarity. Along with the experimentally characterized cyclononatetraenyl (1CH−) and azonide (1N−) anions, the phosphonide ion (1P−, which has not been reported before), favors planar (C2v) symmetry. All the other heteronins are nonplanar in order to alleviate ring strain. Comparisons of the neutral planar heteronins (constrained to C2v symmetry) show the extent to which heteroatoms like P and S, as well as N and O (in oxonin, 1O), can participate in the cyclic electron delocalization. Due to hyperconjugation, the C2v‐symmetric 9,9‐distannylcyclononatetraene 1C(SnH3)2 is moderately aromatic, in contrast to 1CH2, which is a nonaromatic, conjugated system. The planar C2v‐symmetric 1BH and 1AlH and 1CF2 are antiaromatic, like the planar form of 1CH+. Annelation with three‐membered rings resulted in planar heteronins. The sole exception was phosphonin (8PH), but the barrier to planarity decreased to 1.8 kcal/mol in 8PR, due to the bulky R: 2,6‐di‐tert‐butylphenyl substituent at the phosphorus atom. Among the 8π heteronins, only the previously reported 1CH+ is Möbius‐aromatic; 1BH, 1AlH and 1CF2 also have C2 structures but are nonaromatic due to large torsional angles which preclude cyclic delocalization. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Mechanisms and Substituent Effects of Metal-Free Bioorthogonal Reactions

“…Cyclopentadienes have long been studied as diene partners in Diels–Alder reactions. Studies by Schleyer et al showed that substituents on the C-5 position affect the electronic properties of the cyclopentadiene π-system via hyperconjugation. − σ-acceptors, and in particular fluorine atoms, induce negative hyperconjugation resulting in a pseudo 4π-electron antiaromatic system (Figure a). ,− Some of this antiaromatic destabilization is offset by distortion of the C-X bond away from the plane of the diene (Figure b). , In contrast, electron-donating groups (i.e., silyl-substituents) favor an aromatic character of the diene. The degree of (anti)­aromaticity of cyclopentadienes directly affects the distortion energy in the cycloaddition transition state and therefore the rate of the reaction …”

“…Most 4 H- pyrazoles require heating or acid catalysis to react with strained alkenes or alkynes. − However, strategically positioning σ-accepting groups (e.g., -F) at the C-4 position allow such reactions to proceed at room temperature by inducing hyperconjugative antiaromaticity (Figure a). ,− Recently, 4,4-difluoropyrazoles (DFP) were proposed as dienes suitable for use in bioorthogonal IEDDA reactions. , The electrophilic geminal fluorine groups invoke hyperconjugative antiaromaticity which destabilizes the ground state and reduces the energy required to distort the diene in the transition state of the reaction with dienophiles. BCN reacted faster with diphenyl-DFP ( k 2 = 5.2 M –1 s –1 ) than with 3,6-diphenyltetrazine ( k 2 = 3.2 M –1 s –1 ) .…”