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. 2024 Oct 21;63(43):e202411166.
doi: 10.1002/anie.202411166. Epub 2024 Sep 17.

Molecular Editing of Pyrroles to Benzenes/Naphthalenes by N2O Deletion

[Article in German]
Wen-Jie Xiao  1 , Cheng-Xin Li  1 , Jing-Yi Lv  1 , Shan Xu  1 , Wen-Xia Shi  1 , Xiao-Can Su  1 , Jia-Ying Xue  1 , Bao-Qin Huang  1 , Yong Zou  1 , Ming Yan  1 , Xue-Jing Zhang  1
Affiliations

Molecular Editing of Pyrroles to Benzenes/Naphthalenes by N2O Deletion

[Article in German]
Wen-Jie Xiao et al. Angew Chem Int Ed Engl. .

Abstract
in English, German

A molecular editing reaction for converting pyrrole rings into benzene rings through a sequential pathway of Diels-Alder and cheletropic reactions was developed. The nitrogen atom in a N-bridged intermediate is eliminated in the form of N2O by a strain-releasing pathway, ultimately leading to the formation of substituted benzene and naphthalene derivatives.

Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially, N‐Boc pyrroles and alkynes are converted into N‐bridged compounds through a Diels–Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site‐selective peripheral editing of the benzene ring. Furthermore, this proof‐of‐concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.

Keywords: late-stage functionalization; molecular editing; nitrogen deletion; skeletal editing; strain-release.

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References

    1. None
    1. R. Rossi, M. Lessi, C. Manzini, G. Marianetti, F. Bellina, Synthesis 2016, 48, 3821–3862;
    1. Z. Hosseinzadeh, A. Ramazani, N. Razzaghi-Asl, Curr. Org. Chem. 2018, 22, 2256–2279;
    1. E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57, 10257–10274;
    1. M. Kvasnica, M. Urban, N. J. Dickinson, J. Sarek, Nat. Prod. Rep. 2015, 32, 1303–1330.

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