11H-Benzo[4,5]imidazo[1,2-a]indol-11-one as a New Precursor of Azomethine Ylides: 1,3-Dipolar Cycloaddition Reactions with Cyclopropenes and Maleimides

Abstract

The possibility of generating azomethine ylides from 11H-benzo[4,5]imidazo[1,2-a]indol-11-one and amino acids is shown for the first time. Based on the cycloaddition reactions of these azomethine ylides with cyclopropenes and maleimides, cyclopropa[a]pyrrolizines, 3-azabicyclo[3.1.0]hexanes, and pyrrolo[3,4-a]pyrrolizines spiro-fused with a benzo[4,5]imidazo[1,2-a]indole fragment were synthesized. Spirocyclic compounds were obtained in moderate to good yields, albeit with poor diastereoselectivity. Density functional theory calculations were performed to obtain an insight into the mechanism of the 1,3-dipolar cycloaddition of 11H-benzo[4,5]imidazo[1,2-a]indol-11-one-derived azomethine ylides to cyclopropenes. The cytotoxic activity of some of the obtained cycloadducts against the human erythroleukemia (K562) cell line was evaluated in vitro by MTS-assay.

Theoretical Study of the Mechanism of the Formation of Azomethine Ylide from Isatine and Sarcosine and Its Reactivity in 1,3-Dipolar Cycloaddition Reaction with 7-Oxabenzonorbornadiene

“…While the syntheses of pyrrolidines utilizing the formation of azomethine ylides from carbonyl compounds and sarcosine have been described, mechanistic studies are scarce. As far as we are aware, published computational studies are focused on the regio- and stereoselectivities of 1,3-dipolar cycloadditions [ 5 , 6 ], while studies which explore the full reaction mechanism and, particularly, the formation of azomethine ylides are rather limited [ 7 ].…”

Density Functional Theory Calculations: A Useful Tool to Investigate Mechanisms of 1,3-Dipolar Cycloaddition Reactions

“…Figure 20. Energy profile of the reaction leading to 126b (black dotted line) or 126b_ent (red dotted line).The azomethine ylides 129, obtained from the tetracyclic ketone 11H-benzo[4,5]imidazo[1,2-a]indol-11-one 127 and L-proline 128, have been utilized by Filatov et al[56] to synthesize several spiro-heterocyclic compounds when they react with cyclopropenes 130 or maleimide 131, which are differently substituted (Scheme 36).…”