Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones: Synthesis, NMR and single-crystal X-ray diffraction studies of novel warfarin analogues

• Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones.
• Synthesis of new warfarin derivatives showing tautomeric equilibrium in solution.
• NMR proved the major warfarin acyclic open-form and cyclic hemiketal diastereomers.
• Single crystal X-ray evidenced the major crystalline warfarin acyclic open-form.
• The diastereoselective organobase catalyzed synthesis of bicyclic ketal warfarins.

The synthesis of a new series of warfarin analogues by convenient organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin to chalcone derivatives is described. 1H NMR spectroscopy evidenced the presence of a predominant acyclic open-form together with the cyclic hemiketal tautomers of the resulting Michael adducts. The acyclic open-form has been unequivocally proved by single-crystal X-ray diffraction analysis. The use of the B ring ortho-hydroxychalcone synthons in this reaction has led to a diastereoselective synthesis of warfarin bicyclo[3.3.1]nonane ketal derivatives.

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