Three-Component Condensation of Pyridinium Ylides, β‑Ketonitriles, and Aldehydes with Divergent Regioselectivity: Synthesis of 4,5-Dihydrofuran-3- and 2H‑Pyran-5-carbonitriles

A library of trans-4,5-dihydrofuran-3-carbonitriles was synthesized in a diastereoselective manner in good yields by the three-component reaction of β-ketonitriles, carbonyl- and semistabilized pyridinium ylide precursors, and aldehydes in the presence of piperidine. This one-pot transformation gene...

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Bibliographic Details
Published in:Journal of organic chemistry 2021-06, Vol.86 (11), p.7460-7476
Main Authors: Demidov, Maxim R, Osyanin, Vitaly A, Osipov, Dmitry V, Klimochkin, Yuri N
Format: Article
Language:English
Online Access:Get full text
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Summary:A library of trans-4,5-dihydrofuran-3-carbonitriles was synthesized in a diastereoselective manner in good yields by the three-component reaction of β-ketonitriles, carbonyl- and semistabilized pyridinium ylide precursors, and aldehydes in the presence of piperidine. This one-pot transformation generates two C–C and one C–O bond and proceeds through a cascade Knoevenagel condensation, a Michael addition, and intramolecular SN2 cyclization. Formation of cyclopropanecarbonitrile derivatives, which in some cases were obtained as major products, was found to be a competing reaction. The use of arylglyoxals changes regioselectivity and leads to 2-hydroxy-2H-pyran-5-carbonitriles.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.1c00423