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