Reactivity of 1-arylnitrosoethylenes towards indole derivatives

Abstract

The reactivity of 1-arylnitrosoalkenes toward indole, 1-methylindole, and 3-methylindole is described. In contrast with the previously observed chemical behaviour of 1-(p-bromophenyl)nitrosoethylene towards pyrrole, the studied heterodienes reacted with indole and 1-methylindole to afford E-oximes via hetero-Diels-Alder reactions. The reaction with 3-methylindole also proceeds via cycloaddition giving the corresponding 1,2-oxazine. Quantum chemical calculations, at the DFT level, indicate that 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 this nitrosoalkene and pyrrole. However, the calculated energy of the theoretical Diels-Alder cycloadducts involving indole and pyrrole clearly suggests that the Diels-Alder reaction is privileged in the case of indole. Furthermore, in the case of the indole, the energy difference between reactants and products clearly favors the regiochemistry observed experimentally. Graphical abstract N H N H O N N H N HO Br Br

Recent Advances in the Chemistry of Conjugated Nitrosoalkenes and Azoalkenes

“…Similar calculations were performed to study the chemical behavior of 3-( p -bromophenyl)­nitrosoalkene 1 toward indole derivatives, which were in agreement with a process involving hetero-Diels–Alder reaction (Scheme ). Thus, the combination of 3-arylnitrosoalkenes with pyrrole derivatives favors the conjugate addition pathway.…”

3-(1,2,3-Triazol-4-yl)-β-Carbolines and 3-(1H-Tetrazol-5-yl)-β-Carbolines: Synthesis and Evaluation as Anticancer Agents

“…In our group, the reactivity of nitrosoalkenes towards heterocycles has been extensively studied, and it was thought that it could be explored for the synthesis of functionalized tryptophan analogs [21][22][23]. The nitrosoalkenes are generated in situ through the treatment of αbromooximes with sodium carbonate, followed by the hetero-Diels-Alder reaction with indoles, subsequent 1,2-oxazine ring-opening, and concomitant rearomatization to afford 3-alkylated indoles incorporating an oxime moiety [24,25]. This open-chain oxime is then reduced to afford the desired tryptamine analog.…”

Ethyl 7-Acetyl-8a-methyl-3-(1-phenyl-1H-tetrazol-5-yl)-1,4,4a,5,6,8a-hexahydro-7H-pyrano[2,3-c]pyridazine-1-carboxylate

“…Our contribution to the chemistry of these synthetic scaffolds illustrates the structural diversity that can be achieved by exploring their chemical behavior, whose key feature is the strong electrophilic character. Nitroso-and azoalkenes, including 3-tetrazolyl-and 3-triazolyl derivatives, were used for the alkylation of five-membered heterocycles, namely pyrroles, dipyrromethanes, indoles and furans [2][3][4][5][6][7][8][9][10][11]. Furthermore, new routes to bis(heteroaromatic)methanes have been developed via two consecutive hetero-Diels-Alder reactions (or conjugated additions) of the in situ generated nitrosoalkenes and azoalkenes, namely the synthesis of dipyrromethanes [12,13], bis(indolyl)methanes [14][15][16], bis(pyrazol-1-yl)methanes [17] and tetrapyrrolic compounds [18].…”