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DOI: 10.1055/a-2609-9601
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Fluorinative Difunctionalization of a Cyclooctene-Fused β-Lactam and Cyclooctene-Fused β-Amino Esters

Tamás T. Novák
a   Institute of Organic Chemistry, Stereochemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt. 2, 1117 Budapest, Hungary
b   Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, Hungary
,
Gábor Turczel
c   Centre for Structural Science, HUN-REN Research Centre for Natural Sciences, Budapest, Magyar tudósok krt. 2, 1117 Budapest, Hungary
,
Gábor Hornyánszky
b   Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, Hungary
,
Pál T. Szabó
c   Centre for Structural Science, HUN-REN Research Centre for Natural Sciences, Budapest, Magyar tudósok krt. 2, 1117 Budapest, Hungary
,
Loránd Kiss∗
a   Institute of Organic Chemistry, Stereochemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt. 2, 1117 Budapest, Hungary
,
Santos Fustero
d   Department of Organic Chemistry, University of Valencia, Pharmacy Faculty, 46100-Burjassot, Valencia, Spain
,
Melinda Nonn∗
e   MTA TTK Lendület Artificial Transporter Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Center for Natural Sciences, Hungarian Academy of Sciences, Magyar Tudósok krt. 2, 1117 Budapest, Hungary
f   National Drug Research and Development Laboratory, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt. 2, 1117 Budapest, Hungary
› Author Affiliations
The authors gratefully acknowledge financial support from the Nemzeti Kutatási Fejlesztési és Innovációs Hivatal (NKFIH/OTKA) (National Research, Development and Innovation Office) of Hungary (FK 145394 and K 142266). We are also grateful for the support provided by the European Union (Project no. RRF-2.3.1-21-2022-00015). This work was supported by the János Bolyai Research Scholarship to M.N. from Magyar Tudományos Akadémia (Hungarian Academy of Sciences).
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Abstract

The synthesis of novel arylfluorinated cyclic β-amino acid and β-lactam derivatives is accomplished. Studies on the Pd-catalyzed arylfluorination of the double bond of a cyclooctene-fused azetidine-2-one and various β-amino esters are performed under versatile experimental conditions. The arylfluorinative difunctionalization of a cyclooctene-fused β-lactam, performed with phenylboronic acid in the presence of Selectfluor, palladium diacetate, azacyclic ligands and different solvents, gave a separable mixture of fluorinated and non-fluorinated products. In contrast, arylfluorination of cyclooctane-β-amino esters, performed under similar conditions, proceed with full regio- and stereoselective control, leading to single phenyl-fluorinated products. Possible synthetic pathways for these transformations are also proposed.

Keywords

amino acids - arylation - difunctionalization - fluorine - lactams

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2609-9601.
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Publication History

Received: 11 April 2025

Accepted after revision: 14 May 2025

Accepted Manuscript online:
14 May 2025

Article published online:
11 June 2025

© 2025. Thieme. All rights reserved

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