Transferring Substituents from Alkynes to Furans and Pyrroles through Heteronorbornadienes as Intermediates: Synthesis of β-Substituted Pyrroles/Furans

The use of 7-oxa/azanorbornadienes as synthetic intermediates for the preparation of 3/4-substituted (beta-substituted) furans/ pyrroles is presented. The method lies in the inverse electron demand Diels-Alder (iEDDA) cycloaddition between a substituted heteronorbornadiene and an electron-poor tetrazine followed by spontaneous fragmentation of the resulting cycloadduct via two retro-Diels-Alder (rDA) reactions affording a beta-substituted furan/pyrrole. The scope of this tandem iEDDA/rDA/rDA reaction was explored in the preparation of 29 heterocycles. A one-pot procedure starting directly from the alkyne precursors of the heteronorbornadiene intermediates is also described.

Automated summary

This paper presents the use of 7-oxa/azanorbornadienes as synthetic intermediates for the preparation of 3/4-substituted furans/pyrroles. The method involves the inverse electron demand Diels-Alder (iEDDA) cycloaddition and retro-Diels-Alder (rDA) reactions, resulting in the synthesis of beta-substituted furans/pyrroles. The study explores the application of this method in the preparation of 29 heterocycles and proposes a one-pot procedure.