Synthesis Of α-Pyrones Via Carboxylative Cyclization Of Propenyl Ketones With Carbon Dioxide

Due to the continuous consumption of the limited oil resources, utilization of carbon dioxide as a nontoxic, cheap, easily accessible and renewable C1 resource has attracted more and more attentions. Transformation of carbon dioxide as a carboxylative reagent into high value-added fine chemicals has also drawn much attentions of chemical researchers. However, the use of reactive organometallic reactants and transition-metal catalysts usually is the precondition for CO2-incorporaing reactions due to the thermodynamic and kinetic stabilities of carbon dioxide. The use of transition metals involves many drawbacks including high cost, toxicity, and raise the crucial issue of metal impurity residuum in the resultant product. Therefore, it is highly desirable to develop an alternative transition-metal-free method for the conversion of carbon dioxide into fine chemicals.a-Pyrone is a commonly observed structural unit in many naturally occurring products that show a broad range of biological and pharmaceutical activities. The disadvantages for the present synthetic methods are multistep, low-yielding and requiring the participation of transition-metals. This thesis mainly focused on transition-metal-free reaction of carbon dioxide with substituted propenyl ketones to give a-pyrone compounds. We found that a suitable base could conduct deprotonation at y position of ketones to form an enol intermediate, which reacted with carbon dioxide to form a carboxylate intermediate. The followed cyclization reaction delivered the carboxylative cylization products.The reaction of β-methylchalcone with carbon dioxide was initially chosen as a model reaction, and the following optimal reaction conditions were identified:4.0 equivalents of cesium fluoride as base, CO2 (3.0 MPa) in DMSO at 100 ℃ for 24 h. Under this conditions, a variety of substituted propenyl ketones conducted carboxylative cyclization reaction smoothly to give a-pyrones in moderate to good yields. The reaction of C18O2 was carried out to gain insight into the mechanism, which revealed that one oxygen atoms taken off during the reaction come from the carbon dioxide. This carboxylative cyclization of substituted 1-propenyl ketones via y-carboxylation using carbon dioxide provides a transition-metal-free and straightforward access to various a-pyrone compounds of high biological importance in moderate to good yield.