Molecular Iodine-Catalyzed C3-Alkylation Of 4-Hydroxycoumarins

Molecular iodine-catalyzed reactions have been used widely in organic chemistry and pharmaceutical chemistry as one of the most important catalysts in organic synthesis. Molecular iodine is kind of a special Lewis acid, which has distinctive catalytic properties comparing with usual protonic acids and slats of heavy metals. For example, iodine-catalyzed reactions are in high selectivity and yield in shorter reaction time. Moreover, the reaction can proceed in mild condition with simple operation. In this thesis, new development of molecular iodine-catalyzed reaction in organic chemistry has been summarized.In this thesis, molecular iodine-catalyzed C3-alkylation of 4-hydroxycoumarins is reported. Corresponding C3-alkylated 4-hydroxycoumarin derivatives are obtained in good to excellent yields in optimized condition, by the alkylation reaction of 4-hydroxycoumarins with secondary benzyl alcohols at 50℃, using MeNO₂ as the solvent. We also use enantiomeric pure diaryl-propargyl alcohol in this method to probe the reaction mechanism of this I₂-catalyzed alkylation reaction. A possible mechanism based on carbonium ion intermediate is proposed. Applying this reaction condition in drug synthesis, anticoagulated blood drug coumatetraly is obtained in 44% yield. By using this reaction as the key step, multi-substituted pyranocoumarins can easily be synthesized in a new one-pot procedure.