Synthesis of Naturally Occurring Cyclohexene Rings Using Stereodirected Intramolecular Diels-Alder Reactions Through Asymmetric 1,3-Dioxane Tethering

The utility of the readily available asymmetric 1,3-dioxane template in intramolecular Diels-Alder reactions is reported. The 1,3,9-decatrienoates substrates gave predominantly the endo-boat products, with minor amounts of the exo-boat isomer. Various substitutions (14 examples) were introduced and the results gave an indication of the scope and also a few limitations of the method. In particular, the approach was applicable to (E,Z)-diene substrates, for which good yields and selectivities were obtained. By applying suitable substrates, we describe the successful synthesis of valuable intermediates for the total synthesis of the diterpene harringtonolide (1) and the pyrrocidine polyketides (2), affording the appropriate stereochemistry of the natural product within the highly functionalized cyclohexene ring system. This is the first time that an asymmetric synthetic approach toward both compound series has been reported.