Aza‐[4+3] and Aza‐[3+2] Annulations for Synthesis of Dihydroazepines and Dihydropyrroles from Alkynes, Sulfonyl Azides, and 1,3‐Dienes

Abstract

We report aza-[4+3] annulation through sequential [3+2]-[2+1] cycloadditions-aza-Cope rearrangement for the synthesis of dihydroazepines. Aza-[3+2] annulation was achieved through [3+2]-[2+1]-aza-Cope rearrangement-1,3migration or [3+2]-[2+1]-Clock rearrangement, leading to the formation of dihydropyrroles. In addition, dihydroazepines thermally 1,3-migrated to give dihydropyrroles. This method affords a straightforward synthetic pathway from simple triazoles to produce dihydroazepines and dihydropyrroles together with N 2 as the single byproduct. This procedure can be successfully applied to a one-pot process starting from terminal alkynes, azides, and dienes.Azaheterocycles are a highly important class of compounds due to their biological activities and pharmaceutical applications. [1] In particular, dihydroazepines, dihydropyrroles, and pyrroles are constituents of a valuable privileged structure in organic chemistry. [2] For this reason, the development of efficient synthetic methods for producing multisubstituted azaheterocyclic compounds from simple and easily accessible starting materials has been continuously required. [3] Now, we report an efficient aza-[4+3] annulation and aza-[3+2] annulation starting from terminal alkynes, sulfonyl azides, and 1,3-dienes in one-pot (Scheme 1).Recently, 1-sulfonyl-1,2,3-triazoles, which are easily prepared from copper-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with sulfonyl azides, have been extensively investigated as precursors of a-imino metal carbenes. [4] The high reactivity of a-imino metal carbenes toward nucleophiles is caused by the intrinsically electrophilic properties of the metal carbene species. In addition, a-imino metal carbenes can react with electrophiles because the nitrogen atom of the a-imino group is inherently nucleophilic. Accordingly, these amphiphilic a-imino metal carbenes smoothly react with nitriles, [5]

Rhodium(I)‐Catalyzed Intermolecular Aza‐[4+3] Cycloaddition of Vinyl Aziridines and Dienes: Atom‐Economical Synthesis of Enantiomerically Enriched Functionalized Azepines

“…For example, Jeffrey and co‐workers, have carried out seminal studies on the cycloaddition of transient aza‐oxyallylic cations with dienes. The research groups of Sarpong, Tang,, and Lee have independently demonstrated elegant rhodium(II)‐catalyzed formal [4+3] cycloaddition reactions of alkenyl rhodium(II) iminocarbene intermediates with dienes, thus providing efficient access to 2,5‐dihydroazepines. Moreover, azomethine ylides have also been utilized in [4+(aza‐3C)] cycloaddition reactions by the Wang group .…”

Recent Advances in the Synthesis of Heterocycles and Related Substances Based on α‐Imino Rhodium Carbene Complexes Derived from N‐Sulfonyl‐1,2,3‐triazoles

“…Very shortly thereafter,as imilar work was reported independently by Lee and co-workers. [15] An intramolecular [4+ +3] cycloadditiono fd ienyltriazoles was reportedb yS arpong and co-workers( Scheme 7). [16] In this work, 3,4-fused dihydroazepines 29 were obtained through an intramolecular [4+ +3] cycloaddition reaction.…”

“…Mechanistically, it was proposed that cyclopropylaldimine 27 is formed first in all cases and is then converted into either the 2,5‐dihydroazepine or the 2,3‐dihydropyrrole. Very shortly thereafter, a similar work was reported independently by Lee and co‐workers …”

Chemoselective Aza-[4+3]-annulation of N-Perfluoroalkyl-1,2,3-triazoles with 1,3-Dienes: Access to N-Perfluoroalkyl-Substituted Azepines

“…31 Application of highly bulky Rh 2 (S-PTAD) 4 was reported as a way of switching the reaction outcome to the [4+3]-pathway. 32 However, this catalyst is rather expensive, and (Z)-1-substituted 1,3-dienes are not easily available, which makes the synthesis of 2,5dihydroazepines starting from (E)-1-substituted 1,3-dienes a challenging task. Herein, we report the chemoselective synthesis of hitherto unknown but highly attractive N-perfluoroalkylated azepine derivatives via the aza-[4+3]-annulation of N-perfluoroalkyl-1,2,3-triazoles with both (E)-1-substituted and 2-substituted dienes (Scheme 1).…”