Cobalt-Catalyzed Carbon-Carbon Bond Formation: Synthesis and Applications of Enantlopure Pyrrolidine Derlvatlves

摘要

In the presence of cobalt catalysts and tet-ramethylethylenediamine (TMEDA), the iodine atom in (S)-2-(iodomethyl)pyrrolidines was replaced by an aryl or an alkynyl group from the corresponding Grignard reagent, and the coupling products were obtained in good to excellent yields (16 examples; 75-94% yields). The scope and limitations of this protocol were examined. The stereochemistry of the pyrrolidines was unaffected by the reaction conditions. The coupling products are important buildingblocks of phenanthroindolizidine alkaloids. Palladium-catalyzed formal [4 + 2] cycloaddition of 2,2'-diio-dobiphenyl with the thus-generated (S)-2-(3-trime-thylsilyl-2-propynyl)pyrrolidine gave a good yield of the desilylated phenanthrene, which was then converted into unnatural (+)-(5)-tylophorine by the Pictet-Spengler cyclization.