Fluorinative Difunctionalization of a Cyclooctene-Fused β-Lactam and Cyclooctene-Fused β-Amino Esters

Tamás T. Novák; Gábor Turczel; Gábor Hornyánszky; Pál T. Szabó; Loránd Kiss; Santos Fustero; Melinda Nonn

doi:10.1055/a-2609-9601

Synthesis, Inhaltsverzeichnis

Synthesis 2025; 57(15): 2391-2398
DOI: 10.1055/a-2609-9601

paper

Fluorinative Difunctionalization of a Cyclooctene-Fused β-Lactam and Cyclooctene-Fused β-Amino Esters

Authors

Tamás T. Novák

^aInstitute of Organic Chemistry, Stereochemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt. 2, 1117 Budapest, Hungary

^bDepartment 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

^cCentre for Structural Science, HUN-REN Research Centre for Natural Sciences, Budapest, Magyar tudósok krt. 2, 1117 Budapest, Hungary
Gábor Hornyánszky

^bDepartment 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

^cCentre for Structural Science, HUN-REN Research Centre for Natural Sciences, Budapest, Magyar tudósok krt. 2, 1117 Budapest, Hungary
Loránd Kiss∗

^aInstitute of Organic Chemistry, Stereochemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt. 2, 1117 Budapest, Hungary
Santos Fustero

^dDepartment of Organic Chemistry, University of Valencia, Pharmacy Faculty, 46100-Burjassot, Valencia, Spain
Melinda Nonn∗

^eMTA 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

^fNational Drug Research and Development Laboratory, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt. 2, 1117 Budapest, Hungary

Abstract

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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

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Referenzen

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