Cobalt catalyzed [4+2+2] homo Diels-Alder chemistry and application in the formal synthesis of (+/-)-portulal

The goal of this research is to develop the transition metal catalyzed [4+2+2] homo Diels-Alder reaction into a useful synthetic tool in organic chemistry. Two major problems in this cycloaddition of norbornadienes and butadienes have been solved. First, the discovery of an efficient catalyst for the cycloaddition to form tetracyclo[5.4.0.02,4.0 3,7]undec-9-enes has been accomplished. Second, the opening of the cycloadducts to synthetically useful, specific bicyclic core structures has also been achieved.; The combination COX2/ligand/reducing agent/Lewis acid generates effective catalysts for the transition metal catalyzed [4+2+2] homo Diels-Alder reactions of norbornadienes with butadienes, leading to a new system which is highly effective at room temperature: CoI2/dppe/Zn/ZnI2. This catalyst shows broad functional group tolerance over a range of norbornadienes, and selectivity over other pathways such as butadiene polymerization and norbornadiene oligomerization. The Lewis acid effect in these cobalt-catalyzed [4+2+2] cycloadditions has also been probed.; The cyclopropane ring in 5-hydroxy cycloadducts has been selectively activated and transformed into tricyclo[5.4.0.03,7]undecan-5-ones in excellent yields, by a platinum (II) reagent---Zeise's dimer. Oxidative opening at the ketone by oxygen insertion (Baeyer-Villiger reaction) offers a highly efficient way to prepare bicyclo[4.2.1]nonanes, the core structure of a variety of natural products including the antitumor mediterraneols.; The 5-alkoxy substituted cycloadducts were transformed into tricyclo[6.2.1.0 3,9]undec-2-enes under Zeise's dimer catalysis, and the corresponding olefins upon ozonolysis gave the highly substituted, stereochemically defined perhydroazulene (bicyclo[5.3.0]decane) derivatives. This methodology has been successfully applied to the synthesis of methyl 5-tert-butyldiphenylsiloxy-10-cyano-9-methyl-bicyclo[5.3.0]decan-7-carboxylate, a key core structure suitably functionalized for conversion into the plant growth regulator portulal, a diterpenoid. The formal total synthesis of (+/-)-portulal was then completed. The asymmetric synthesis of portulal is also achievable based on the newly developed lipase resolution of endo-7- tert-butoxynorborn-2-en-5-ol to provide chiral starting material for the synthesis.