A Urease-Catalyzed Three-Component Reaction for the Efficient and Sustainable Synthesis of Highly Substituted 4H-Pyrans in Water as the Solvent

Mahmoud Abo El Makarim Saleh; Jürgen Conrad; Wolfgang Frey; Uwe Beifuss

doi:10.1055/s-0043-1775396

Synthesis, Table of Contents

Synthesis 2025; 57(02): 457-471
DOI: 10.1055/s-0043-1775396

paper

Special Topic Dedicated to Prof. H. Ila

A Urease-Catalyzed Three-Component Reaction for the Efficient and Sustainable Synthesis of Highly Substituted 4H-Pyrans in Water as the Solvent

Mahmoud Abo El Makarim Saleh

^aInstitut für Chemie, Universität Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany

,

Jürgen Conrad

^aInstitut für Chemie, Universität Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany

,

Wolfgang Frey

^bInstitut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany

,

Uwe Beifuss ∗

^aInstitut für Chemie, Universität Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany

› Author Affiliations

Abstract

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Dedicated to Professor Hiriyakkanavar Ila on the occasion of her 80^th birthday

Abstract

An efficient urease-catalyzed approach for the synthesis of highly substituted 6-amino-4H-pyran-3-carbonitriles based on the formation of three bonds in one step is developed. This unprecedented three-component reaction between one molecule of an aromatic aldehyde and two molecules of an aroylacetonitrile proceeds by employing commercially available urease from jack bean (Canavalia ensiformis) as the catalyst in water at 65 °C to deliver the desired 4H-pyrans in yields of up to 92%. The transformation is proposed to occur via a domino Knoevenagel condensation/1,4-addition/O-cyclization/tautomerization sequence, providing a practical and sustainable approach to 6-amino-4H-pyran-3-carbonitriles from commercially available substrates. Full and unambiguous structural elucidation of all the products is achieved by means of NMR spectroscopy and X-ray crystal structure analysis.

Key words

heterocycles - 4H-pyrans - multicomponent reaction - biocatalysis - enzymes - urease - green chemistry

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References

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