Three-Component Domino Process for the Pyrrolizine Skeleton via [3 + 2]-Cycloaddition–Enamine Cyclization Triggered by a Gold Catalyst

Abstract

Pyrrolizines are bicyclic fused azaheterocycles with a bridgehead nitrogen contained in a core skeleton and are often found in biologically active compounds. Despite their importance, there have been few reports on concise and flexible syntheses of pyrrolizines. A novel one-pot, convergent method is described for pyrrolizines by simple mixing of iminoesters, acetylenes, and dipolarophiles in the presence of a cationic gold catalyst and an acid additive. This domino process affords multisubstituted pyrrolizines without handling unstable intermediates.

Isothiourea-catalysed enantioselective pyrrolizine synthesis: synthetic and computational studies

“…2b ). 14 Catalytic enantioselective methodologies that enable efficient access to this desirable structural motif are relatively limited. Within this area, Cho and co-workers showed that an enantioselective organocatalysed Michael addition-aldol approach could generate functionalised pyrrolizines with excellent diastereo- and enantiocontrol (18 examples, >95 : 5 dr and 95 : 5 to 99 : 1 er, Fig.…”

Synthesis of Substituted Pyrrolo[2,1-a]isoquinolines by Gold-Catalyzed Domino Cyclization of Alkynyl Iminoesters

“…In summary, we have accomplished a novel, double cyclization method for biologically important pyrroloisoquinoline skeleton based on the Au-catalyzed azomethine ylide formation strategy. 10 This one-pot cyclization system could furnish highly substituted pyrroloisoquinolines and can be applied for the preparation of optically active derivatives under auxiliary-controlled diastereoselective process. Merged with the findings obtained in our three-component…”

“…pyrrolizine formation reaction, 10 this novel strategy for pyrroloisoquinolines is now employed for synthetic studies on biologically active polycyclic alkaloids in our laboratory.…”

“…8aa In this context, we focused on our recent work in regard to the gold-catalyzed intermolecular three-component domino reaction via azomethine ylide formation under mild conditions (Scheme 1). 10 The reaction was triggered by a selective activation of triple bond on 3 with gold catalyst. Nucleophilic attack of nitrogen on iminoester 2 onto the activated triple bond produced a vinyl gold complex 6, from which a gold catalyst was regenerated by protodeauration with the acidic α-proton of the ester 6 and, at this time, reactive azomethine ylide 7 was produced in situ.…”

Regio‐ and Stereoselective Multicomponent Synthesis of Novel Chromeno‐Annulated Pyrrolizine and Thiazolizine Scaffolds via 1,3‐Dipolar Cycloaddition Reactions

“…In recent years, the catalytic pyrrolizine syntheses has involved multi‐step reaction processes, an example where Saravanan and co‐workers has described the synthesis of chromenopyrrolidines in (Scheme a) . To report further, Matsuya and co‐workers have depicted the synthesis of pyrrolizines in (Scheme b) . Again, Kanchithalaivan and Kumar's group has developed a method for the synthesis of spiro‐oxindole pyrrolizines derivatives shown in (Scheme c) …”