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

• DOI: 10.1016/j.molstruc.2015.03.069
• Publication Date: 2015-04-05T20:27:36Z
• Authors: Oualid Talhi; José A. Fernandes; Diana C.G.A. Pinto; Filipe A. Almeida...; Artur M.S. Silva
• Keywords: CONFORMATIONS; DERIVATIVES; ANTICOAGULATION; THERAPY; 01 natural sciences; 0104 chemical sciences

Abstract 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.