Palladium-catalyzed Asymmetric Difunctionalization Of 1,3-dienes

1,3-Dienes,including feedstock chemicals such as butadiene and isoprene,are easily accessible chemicals.Palladium-catalyzed difunctionalization of 1,3-dienes is one of the most important transformations of 1,3-dienes.Various difunctionalization reactions of 1,3-dienes,such as alkylation,arylation,amination,etc,could be realized through either Pd(0)catalysis or Pd(?)catalysis.Asymmetric difunctionalization of 1,3-dienes can be employed for the rapid construction of a series of important skeletons such as chiral indolines,chiral isochromans,and chiral indanes,which are widely found in natural products and drugs.In this disertation,we focus on the asymmetric palladium-catalyzed difunctionalization of 1,3-dienes,employing readily available starting materials such as o-iodoanilines,dimethyl o-iodomalonates and phenylureas.First,employing o-iodoanilines as the reactants,in the presence of palladium acetate and BINOL-derived phosphoramidite ligands,we have developed a palladium(0)-catalyzed asymmetric aryl amination of 1,3-dienes,obtaining chiral indoline derivatives.In the meantime,employing o-iodobenzyl alcohols,we have realized the palladium-catalyzed asymmetric aryl alkoxylation of 1,3-dienes,yielding chiral isochroman derivatives with high efficiency.Secondly,employing dimethyl ortho-iodomalonates as the substrates,we have developed the palladium acetate/BINOL-derived phosphoramidite ligand-catalyzed asymmetric aryl alkylation of 1,3-dienes,furnishing important chiral indane skeletons.Using DFT calculations,we have also investigated the reaction mechanism focusing on the details of the stereocontrol by the phosphoramidite ligands.Finally,employing palladium(?)p-toluenesulfonate and chiral sulfoxide-oxazoline ligands,we have achieved a palladium(?)-catalyzed asymmetric aryl amination of 1,3-dienes using arylureas,providing an alternative strategy to obtain chiral indoline derivatives from simple starting materials.The.combination of Pd(?)and chiral sulfoxide-oxazoline ligand has provided a powerful tool for the development of asymmetric cascade reactions involving C-H activation of electron-rich arenes.