General acid-mediated aminolactone formation using unactivated alkenes

David Just; Carlos R. Gonçalves; Uroš Vezonik; Daniel Kaiser; Nuno Maulide

doi:10.1039/d3sc04073a

General acid-mediated aminolactone formation using unactivated alkenes

David Just
, Carlos R. Gonçalves
, Uroš Vezonik
, Daniel Kaiser
, Nuno Maulide (Corresponding author)

Department of Organic Chemistry

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

Spirocyclic butyrolactones and butenolides are widespread structural motifs in bioactive substances. Despite their prevalence, a simple method ensuring their direct preparation from exocyclic alkenes, ideally in a late-stage context, remains elusive. Herein, we report direct aminolactone formation using unactivated alkenes which addresses this gap, employing cheap and readily available reactants. The method relies on the hijacking of a cationic aminoalkylation pathway and affords (spiro)aminolactones with excellent functional group tolerance and chemoselectivity. The synthetic versatility of the products is demonstrated through a range of transformations, notably exploiting stereospecific rearrangement chemistry to produce sterically congested scaffolds.

Original language	English
Pages (from-to)	10806-10811
Number of pages	6
Journal	Chemical Science
Volume	14
Issue number	39
DOIs	https://doi.org/10.1039/d3sc04073a
Publication status	Published - 28 Sept 2023

Funding

This research was funded by the Austrian Science Fund (FWF P32607), the European Research Council (ERC CoG VINCAT 682002) and the Fundação para a Ciência e Tecnologia (FCT SFRH/BD/141844/2018 fellowship to C. R. G.) is highly appreciated. We are very grateful to the University of Vienna for continued support of our research programs. Support by A. Prado-Roller and T. Grüne (both from University of Vienna) with crystal structure determination, and by E. Turhan, L. Pollesböck, C. Itzenthaler, S. Armentia-Matheu, C.-S. Hsu, as well as I. Mosiagin (all from University of Vienna) with preliminary and ancillary experiments is gratefully acknowledged. We also acknowledge Prof. H. Martin (University of Vienna) for assistance regarding the stereochemical properties of substituted (spiro)aminolactones.

Austrian Fields of Science 2012

104015 Organic chemistry

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10.1039/d3sc04073a

https://phaidra.univie.ac.at/o:2066689Licence: CC BY 3.0

Cite this

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title = "General acid-mediated aminolactone formation using unactivated alkenes",

abstract = "Spirocyclic butyrolactones and butenolides are widespread structural motifs in bioactive substances. Despite their prevalence, a simple method ensuring their direct preparation from exocyclic alkenes, ideally in a late-stage context, remains elusive. Herein, we report direct aminolactone formation using unactivated alkenes which addresses this gap, employing cheap and readily available reactants. The method relies on the hijacking of a cationic aminoalkylation pathway and affords (spiro)aminolactones with excellent functional group tolerance and chemoselectivity. The synthetic versatility of the products is demonstrated through a range of transformations, notably exploiting stereospecific rearrangement chemistry to produce sterically congested scaffolds.",

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AU - Just, David

AU - Gonçalves, Carlos R.

AU - Vezonik, Uroš

AU - Kaiser, Daniel

AU - Maulide, Nuno

N1 - Accession Number: WOS:001077906300001 PubMed ID: 37829023

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AB - Spirocyclic butyrolactones and butenolides are widespread structural motifs in bioactive substances. Despite their prevalence, a simple method ensuring their direct preparation from exocyclic alkenes, ideally in a late-stage context, remains elusive. Herein, we report direct aminolactone formation using unactivated alkenes which addresses this gap, employing cheap and readily available reactants. The method relies on the hijacking of a cationic aminoalkylation pathway and affords (spiro)aminolactones with excellent functional group tolerance and chemoselectivity. The synthetic versatility of the products is demonstrated through a range of transformations, notably exploiting stereospecific rearrangement chemistry to produce sterically congested scaffolds.

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General acid-mediated aminolactone formation using unactivated alkenes

Abstract

Funding

Austrian Fields of Science 2012

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