Studies on the tandem oxy-CopeeneClaisen reaction Applications of the hydroxy-directed Diels-Alder reaction towards the total synthesis of havellockate and synthesis of isovelleral analogues

Abstract

The synthesis of decalin systems possessing a quaternary carbon at C-9 was achieved via the tandem oxy-Cope/ene/Claisen rearrangement. Depending on the substitution pattern of the allyl ether 1, different reaction pathways may be followed to generate the decalin cores. In the case of 1,2-divinylchyclohexanol having a 1,2-disubstituted allyl ether, the tandem reaction afforded the decalin system in good yield. However, trisubstituted allyl ethers produced unique decalin products via a radical 1,3-shift. In addition, microwave irradiation of 1,2-divinylcyclohexanol propargyl ethers generated tetracyclic acetals via the tandem oxy-Cope/ene/Claisen/5-exo dig cyclization.* The scope and limitations of the hydroxy-directed Diels-Alder (HDDA) reaction were studied on 5-membered semicyclic dienes possessing secondary or tertiary allylic alcohols. A temporary magnesium tether provided by MgBr 2·OEt2 or vinylmagnesium bromide was utilized to regio- and stereoselectively control the Diels-Alder reaction. This methodology was applied towards the synthesis of the hydrindane moiety of isovelleral 2 in order to construct its analogues.* As well, the HDDA reaction was applied towards the total synthesis of havellockate 3. The bicyclic core of the natural product was prepared with high regio- and stereocontrol and good yield.* *Please refer to dissertation for diagrams.