| Palladium catalyzed regio- and enantioselective ring openings of vinyl epoxides with carbon and nitrogen centered nucleophiles are developed and optimized. Chiral ligands can control regio- as well as enantioselectivities in the reactions of isoprene monoepoxide. Thus 1,2- rather than 1,4-adducts with carbon nucleophiles such as beta-ketoesters and nitrogen nucleophiles such as PMBNH2 are obtained with excellent enantioselectivities and good yields. The results with beta-ketoesters represent the first examples of such reactions for carbon centered nucleophiles reacting with vinyl epoxides, which are even more remarkable since a quaternary stereocenter is constructed enantioselectively.; The synthetic power of the above methodologies is subsequently demonstrated in the asymmetric syntheses of the cyclopentyl core of viridenomycin and a derivative of vancosamine. The cyclopentyl core of viridenomycin was synthesized in 11 steps and 20.2% overall yield, which contrasts sharply with the two existing routes, the shorter of which required nearly twice as many steps. The derivative of vancosamine is synthesized in 9 total steps and 28.6% overall yield, which is the first asymmetric synthesis of vancosamine derivatives using a non-enzyme-catalyzed enantioselective reaction as the source of chirality.; The total synthesis of marcfortine A and B are also investigated, in which a Pd-catalyzed carboxylative TMM cycloaddition is a key step. The studies are focused on the cyclization of the bicyclo[2.2.2]diazaoctane system. |
