Synthesis Of α-alkylated Ketones

a-Alkylated ketones are a very important class of compounds that have a wide range of pharmacological and physiological activities. One of the most widely used synthetic methods occurs via the reaction of the corresponding ketone enolate species with an alkyl halide. However, these procedures suffer from the toxicity of alkyl halides and the generation of a great amount of harmful waste salts. The development of "hydrogen auto-transfer reaction" makes it possible that researchers can use less toxic alcohols instead of the high poisonous halogenated hydrocarbons as electrophilic reagent to accomplish alkylation reaction. Due to the high atom efficiency, and the formation of water as the only side product, such reactions meet the requirement of green chemistry.In the second chapter, we explored the synthesis of αt-alkylated ketones via one-pot, sequential method. In the presence of [(IPr)AuCl]/AgOTf and [Cp*IrCl2]2/KO’Bu, a series of alkynes were first hydrated to give the corresponding methyl ketones, which in turn were α-alkylated with alcohols. From both synthetic and environmental points of view, the reaction is highly attractive because of easily available starting materials, high atom efficiency and minimal consumption of chemicals and energy. The research will also facilitate the development of one-pot, sequential, catalytic reactions based on "hydrogen autotransfer" (or "hydrogen-borrowing") processes.In the trird chapter, we researched a Cp*Ir complex bearing a functional bipyridonate ligand, which was found to be a highly effective and versatile catalyst for the α-alkylation of ketones with primary alcohols (0.1 equiv of CS2CO3 per substrate, reflux under an air atmosphere for 6 h). Furthermore, this complex also exhibited a high level of catalytic activity for the a-methylation of ketones with methanol. Due to the mild reaction condition, good to excellent yields, the widely suitability for a broad range of substrates with different groups, and operational convenience refluxing under air atmosphere, the reaction according with the demand of green chemistry and has a certain application value.This paper demonstrated two methods for the synthese of α-alkylated ketones from different points of view. These two methods both based on "hydrogen auto-transfer reaction", and facilitate the progress of green chemistry-directed reaction in organic synthesis.