A Stereospecific Alkene 1,2-Aminofunctionalization Platform for the Assembly of Complex Nitrogen-Containing Ring Systems

Yuxiang Zhu; Matthew J S Smith; Wenbin Tu; John F Bower

doi:10.1002/anie.202301262

A Stereospecific Alkene 1,2-Aminofunctionalization Platform for the Assembly of Complex Nitrogen-Containing Ring Systems

Angew Chem Int Ed Engl. 2023 Apr 11;62(16):e202301262. doi: 10.1002/anie.202301262. Epub 2023 Mar 13.

Authors

Yuxiang Zhu¹, Matthew J S Smith¹, Wenbin Tu^{1

2}, John F Bower¹

Affiliations

¹ Department of Chemistry, University of Liverpool, Crown Street, Liverpool, L69 7ZD, UK.
² School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.

PMID: 36812298
DOI: 10.1002/anie.202301262

Abstract

TFA promoted deprotection of O-Ts activated N-Boc hydroxylamines triggers aminofunctionalization-based polycyclizations of tethered alkenes. The processes involve intramolecular stereospecific aza-Prilezhaev alkene aziridination in advance of stereospecific C-N cleavage by a pendant nucleophile. Using this approach, a wide range of fully intramolecular alkene anti-1,2-difunctionalizations can be achieved, including diaminations, amino-oxygenations and amino-arylations. Trends associated with the regioselectivity of the C-N cleavage step are outlined. The method provides a broad and predictable platform for accessing diverse C(sp³ )-rich polyheterocycles of relevance to medicinal chemistry.

Keywords: Alkenes; Aminofunctionalization; Aziridines; Cascade Reactions; Stereospecificity.

Abstract

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