Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts.

Anthony Choi,Rebecca M Morley,Iain Coldham

doi:10.3762/bjoc.15.149

Anthony Choi, Rebecca M Morley + Show 1 more

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https://doi.org/10.3762/bjoc.15.149

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Abstract

Quinolinium salts, Q+-CH2-CO2Me Br− and Q+-CH2-CONMe2 Br− (where Q = quinoline), were prepared from quinolines. Deprotonation of these salts with triethylamine promoted the reaction of the resulting quinolinium ylides (formally azomethine ylides) with electron-poor alkenes by conjugate addition followed by cyclization or by [3 + 2] dipolar cycloaddition. The pyrroloquinoline products were formed as single regio- and stereoisomers. These could be converted to other derivatives by Suzuki–Miyaura coupling, reduction or oxidation reactions.

Highlights

Cycloaddition reactions of azomethine ylides are an important class of pericyclic reactions that give rise to pyrrolidine rings, prevalent in a large number of natural products and bioactive compounds
The most common method for their preparation is by condensation of a secondary amine with an aldehyde to give an iminium ion that loses a proton to give the ylide, or by condensation of a primary amine with an aldehyde to give an imine followed by prototropy or deprotonation to give N-metalated azomethine ylides
To test the feasibility of the reaction of quinolinium salts bearing electron-withdrawing groups other than ketones, we prepared ester 4 [55] and amide 5 by alkylation of quinoline. Arylidenemalononitriles such as 6a are known to undergo related chemistry [41], so we heated this compound with the quinolinium salts in the presence of triethylamine and were pleased to obtain good yields of the adducts 7a–c and 8a,b (Scheme 2)

Summary

Introduction

Cycloaddition reactions of azomethine ylides are an important class of pericyclic reactions that give rise to pyrrolidine rings, prevalent in a large number of natural products and bioactive compounds. Many methods have been used to prepare azomethine ylides that undergo cycloaddition with π-systems, especially electron-poor alkenes to give pyrrolidine products [1-4]. Almost all of the examples of dipolar cycloaddition reactions involving quinolinium salts that have been reported in the literature involve ketones as electron-withdrawing groups to stabilise the intermediate ylide [39-49]; for example, the ketone 1 is known to undergo reaction with alkenes 2 (Z = electronwithdrawing group) to give the tricyclic products 3 (Scheme 1) [41,49].

Results

Conclusion