β-Nitroso-o-quinone methides: potent intermediates in organic chemistry and biology. The impact of the NO group on their structure and reactivity profile: a theoretical insight

The structure and reactivity profiles of prototype o-quinone methides 1, 2 and their β-nitroso analogues 6–9 have been investigated by means of DFT and MP2 calculations. These highly reactive unstable species are generated by oxidative dearomatization of their precursor oximes. The destabilization of their structure is more pronounced in the β-nitroso congeners 7–9. There is only a weak π conjugation across the nitrosoalkene arm. The latter gives rise to E and Z conformations and causes some distortion on the ring σ-frame, while the π-frame is weakly perturbed. The Z conformation is the most stable in all structures. Their geometry is also affected by the o-quinone ring and the 1,2-(7 and 8) and 2,3-(9) isomer pattern. The stability of these conformations is rationalized in terms of ortho- or peri- ring formations. The impact of their geometry profile on their reactivity pattern has been studied by means of reactivity descriptors such as Fukui and Parr functions, chemical potential and hardness, HOMO and LUMO energies and their separation (HOMO–LUMO gap) as well as aromaticity indices such as HOMA and out-of-plane deformability. All descriptors consistently demonstrate that the reactivity is dominated by an E/Z-controlled intramolecular ortho- or peri-cyclization mode to fused 1,2-oxazoles or 1,2-oxazines vs indoles, respectively. Intermolecular primary reactions can occur at the quinone alkene bond or that of the nitrosoalkene arm.