Reactions of Nitrosoalkenes with Dipyrromethanes and Pyrroles: Insight into the Mechanistic Pathway

Abstract

The reactivity of nitrosoalkenes toward dipyrromethanes, pyrrole, and 2,5-dimethylpyrrole is described. 1-(p-Bromophenyl)nitrosoethylene shows a different chemical behavior with these heterocycles than the previously reported reactions of ethyl nitrosoacrylate, which proceeds via a Diels-Alder reaction. 1-(p-Bromophenyl)nitrosoethylene reacts with dipyrromethanes and pyrrole to afford two isomeric oximes via conjugate addition followed by rearomatization of the pyrrole unit. On the other hand, this nitrosoalkene reacts with 2,5-dimethylpyrrole through an initial conjugate addition followed by intramolecular O- and N-nucleophilic addition with the formation of the corresponding bicyclic oxazine and five-membered cyclic nitrone, respectively. Quantum chemical calculations, at the DFT level of theory, indicate that the barriers associated with the Diels-Alder reactions of ethyl nitrosoacrylate are over 30 kJ/mol lower than those that would be required for the cycloadditions of 1-(p-bromophenyl)nitrosoethylene. Thus, calculations predict that the Diels-Alder reaction is privileged in the case of ethyl nitrosoacrylate and point to a different reaction pathway for 1-(p-bromophenyl)nitrosoethylene, corroborating the experimental findings.

Reactivity of 1-arylnitrosoethylenes towards indole derivatives

“…The energy barriers associated with the reactions between 1-(p-bromophenyl)nitrosoethylene and indole and its derivatives are similar to those observed for the reaction between the nitrosoalkene and pyrrole, which was found to take place by a different reaction pathway [7]. In order to understand the different reactivity of indole and pyrrole towards this nitrosoalkene, the structure and energy of the theoretical Diels-Alder cycloadducts formed in each case were investigated.…”

“…Reactivity of 1-arylnitrosoethylenes towards indole derivatives reactivity of 1-(p-bromophenyl)nitrosoethylene towards pyrrole [7], experimental results concerning the reactions between indole, and respective derivatives with the referred nitrosoalkene are compatible with a reaction occurring via Diels-Alder cycloaddition. The transition state (TS) resulting from the endo-and exo-cycloadditions of indole and two of its derivatives (1-methylindole and 3-methylindole) with 1-(p-bromophenyl)nitrosoethylene were investigated at the DFT level.…”

“…The structure and the lowest energy conformations of this nitrosoalkene have been previously investigated [4] at the same level of theory, being the s-trans conformer found to be more stable than the s-cis conformer (DE = 5.6 kJ/-mol). It was also found an increase in the electrostatic moment from s-cis (2.16 D) to s-trans (2.80 D), suggesting a preference for the s-trans-conformer in polar media [7].…”

“…However, we have recently demonstrated that 1-(pbromophenyl)nitrosoethylene (5a) show a different chemical behaviour towards pyrrole (Scheme 2) [7]. Two isomeric oximes are formed which cannot be explained by a process involving hetero-Diels-Alder reaction.…”

The [4+2]‐Cycloaddition of α‐Nitrosoalkenes with Thiochalcones as a Prototype of Periselective Hetero‐Diels–Alder Reactions—Experimental and Computational Studies

“…Within the experimental limits, the formation of nitrones of type 21 a was not observed. [22,31,32] Again, these data reveal that kinetic control of the cycloaddition is responsible for the formation of the experimentally found cycloadduct 19 a.…”