Construction And Application Of ?-Ketothioesters

As an active functional group,1,2-dicarbonyl moieties are widely existed in numerous natural products,pharmaceuticals and analogues.Also,they present broad application in food chemistry and material science.Furthermore,they frequently serve as a valuable synthetic intenrmediate in diverse heterocycles and chiral compounds synthesis.As a consequence,lots of effort has been made to construct these powerful motifs.Thioester,as an "active" ester,has been proved to be one of most powerful and multifunctional acyl-transfer reagent.It could be converted into aldehyde,ketone,carboxylic acid and its derivatives,almost all the carbonyl compounds.Compare with thioester,we would like to construct ?-ketothioester and explore whether it can serve as dicarbonyl transfer reagent.In general,acyl chloride and thiol are employed in traditional synthetic process,which is of high toxicity and pollution.In our group,we have developed a set of methodologies to achieve the sulfur atom transfer reaction from inorganic sulfur source to organic coumpounds.Based on these strategies,we consider constructing ?-ketothioester and exploring its applications.There are two corresponding parts included in this thesis.Part ?.Construction of ?-ketothioester.Employing ?-hydroxy ketone,elemental sulfur and alkyl halide as reactants,we have developed a green synthetic route of ?-ketothioester without transition-metal and odorous thiol.Various functional groups could be compatible in the reaction.Gram-scale synthesis showed that the method was of good practicality.The control experiments and isolated intermediate trapped by radical scavenger proved the possibility of radical pathway.Part ?.Application of ?-ketothioester as dicarbonylation reagent.Dicarbonylation of amines and arylboroxines was achieved respectively untilizing ?-ketothioester as dicarbonyl transfer reagent.The reaction of amines and ?-ketothioester was achieved under quite convenient and mild conditions.Not noly a variety of aliphatic and aromatic amines,but also amino acid esters and triglycine ethyl ester could be converted into corresponding ?-ketoamides smoothly.Through a Pd-catalyzed coupling approach,a-diketones could be constructed by arylboroxines and ?-ketothioesters.By employing bidentate bipyridine as ligand,the decarboxylative byproduct was suppressed.What's more,natrual product Polyandrocarpamide C and candidate drug Indibulin were well synthesized by using our methods.