Palladium(II)-catalyzed 1,4-oxidations of 1,3-dienes : Development of an asymmetric version and synthetic applications

Sammanfattning: In this thesis the development of an asymmetric version and synthetic applications of the Pd(II)-catalyzed 1,4-oxidation of conjugated dienes are described. The thesis is divided into four parts:(i) The first part concerns the design and synthesis of chiral p-benzoquinones as ligands in the Pd(II)-catalyzed 1,4-diacetoxylation. A p-benzoquinone substituted with a tert-butyl group and a chiral sulfoxide was found to be the best ligand. Optimization of the reaction conditions yielded an enantiomeric excess of 45%.(ii) The asymmetric version of the Pd(II)-catalyzed 1,4-dialkoxylation was also examined. In this case a C2-symmetric p-benzoquinone, with aminoalcohols as chiral units, was the best ligand employed in the reaction, and gave enantioselectivities up to 54% ee. The mechanism of the reaction is discussed.(iii) The synthesis of various heterocyclic compounds utilizing the intramolecular version of the 1,4-oxidation is described. In this study hydroxyl or nitrogen groups were used as the internal nucleophile and various alcohols were employed as the second nucleophile. Both spirocycles and fused heterocycles were obtained. When the hydroxyl group was used as the internal nucleophile the products were generated in good to excellent yield with high regio- and stereoselectivities. With nitrogen as the internal nucleophile the regioselectivity was found to be dependent on the nature of the second nucleophile.(iv) In the last part of the thesis the synthesis of epibatidine and its phenyl analogues are described. Here, one of the key-steps is the Pd(II)-catalyzed 1,4-chloroacetoxylation of aryl substituted 1,3-cyclohexadienes giving only one regio- and stereoisomer in moderate to good yields. Another key-step is a stereoselective hydrogenation, which afforded the required 1,2-cis or 1,2-trans relationship between the nitrogen and the aryl substituent.