Development of Catalytic Diels-Alder Reactions Based on Diene Activation Methodology, and Their Synthetic Applications for Biologically Active Cyclohexeneoxides and Carbasugars

The base-catalyzed Diels-Alder (DA) reaction is a unique cycloaddition, which comprises the combination of electron deficient dienophiles and dienes having acidic functional groups that are activated by bases. It is quite opposite to the well-known Lewis acid-catalyzed DA reactions that include electron rich dienes and dienophiles that are activated by Lewis acids or Bronsted acids. In our continuous effort to develop the base-catalyzed DA, we have found that three different classes of compounds, 3-hydroxy-2-pyrone, 3-hydroxy-2-pyridone, and α-tropolone can be used as dienes suitable for the DA reaction. All the base-catalyzed DA reactions we have developed are accelerated by mild amine bases and give the corresponding products in quantitative to moderate yields. As well as acid-catalyzed DA reactions, chiral base catalysts and/or chiral dienophiles provide the enantioselective DA reactions. Because the resulting DA adducts that have various functional groups and rigid bicyclic ring systems, are attractive building blocks for natural products, particularly for cyclohexene oxides and carbasugars, some synthetic applications to give biologically active compounds using the DA adducts are described.