Synthesis Of Thietane Derivatives And Study On Synthesis Of Transition Metal Catalysts

This thesis is mainly focused on the synthesis of thietane and its derivatives which represent a class of’compact molecule’building blocks, and their applications in the modification of anti-tumor kinase inhibitors. The thesis also covers metal-catalyzed green organic reactions. Three chapters are included in the thesis.Part one:The synthesis of thietane derivativesWhen functional group in a drug molecule, such as gem-dimethyl or carbonyl groups, was modified with oxetane, profound changes to the whole molecule including increasing the aqueous solubility, lowing the lipophilicity and reducing the metabolic degradation may be made, which leads to the optimization of the pharmacokinetic profile of the molecule. Such a novel modification method brings us a new surrogate strategy in the optimization of the leading compounds. The thietane is similar in structure to the oxetane but provides more opportunities of modification (by converting sulfide into sulfoxide or sulfone). Herein several’compact molecules’ containing the thietane structure were prepared, and were then introduced them into the side chain modifications of lapatinib. The studies on efficacy, pharmacokinetic profile, and pharmacological properties will be carried out. Part two:Suzuki-Miyaura reaction catalyzed by Pd-D296An anion exchange resin D296-supported palladium nanoparticle catalyst (D296) was prepared by exchanging homogeneous palladium salt with the original anion of the resin and then reducing palladium to its zero-valence state. This catalyst was employed in the Suzuki-Miyaura cross-coupling reaction between aryl bromides and arylboronic acids and exhibited high catalytic activity and stability. The catalyst was stable, could be recycled and could be easily recovered by simple filtration. All above characters indicate that it’s a new and efficient heterogeneous palladium catalyst. Part three:[Cp*IrC2l]2h catalyzed α-alkylation of ketones with primary alcoholsA neat reaction of [Cp*IrCl2]2catalyzed direct a-alkylation of aromatic ketone with primary alcohol in the presence of KOH was performed with water as the only byproduct. Different from the classical method pursuing a-alkylation of ketone, this method is moderate, easy to handle, highly atom efficient and environment friendly. Different kinds of ketones and primary alcohols perform well in this reaction, especially for aryl ketones, for which substituted functional groups in the aromatic rings do not affect the yield significantly. For aliphatic ketones, the yield decreases. The catalytic mechanism may be a mix of successive hydrogen-transfer reactions and aldol condensation.