Application Of Chiral Sulfinamide Phosphine Ligands In Palladium Catalyzed Asymmetric Tandem Heck Reaction

As an atom-economical,step-economical and greener synthetic strategy for the construction of heterocycles,tandem Heck reaction has attracted much recent attention from both academic and industrial researchers,which has been widely used in the synthesis of some natural products and drug active molecules.However,asymmetric tandem Heck reaction is still in the early stage.Consequently,the development of highly efficient catalysts for asymmetric tandem Heck reaction is a relatively novel research area.The dissertation including two parts is concentrated on the synthesis of benzene-fused heterocycles by asymmetric tandem Heck reaction with chiral sulfinamide monophosphine ligands.(1)Pd(0)-catalyzed asymmetric tandem Heck/Sonogashira coupling reactionPd(0)-catalyzed asymmetric tandem Heck/Sonogashira coupling reaction is very challenging due to various possible competitive side reactions.Herein,with N-Me-Xu3 as the chiral ligand,we have developed the first highly chemo-and enantioselective palladium-catalyzed difunctionalization of unactivated alkenes by Heck/Sonogashira sequence for the efficient synthesis of various chiral benzene-fused cyclic compounds bearing an alkynyl all-carbon quaternary stereocenter(47 examples,68-99% yield,88-96% ee).The gram-scale experiment and the versatile transformations of the alkynyl products may have broad applications in the synthesis of valuable natural products and pharmaceuticals containing chiral dihydrobenzofuran skeletons.(2)Pd(0)-catalyzed asymmetric tandem Heck/silanization reactionThe stereoselectivity of the reaction is difficult to control because the racemic reaction can occur quickly without ligands,and ligands will slow down the rate of reaction.Herein,with N-Me-Xu4 as the chiral ligand and hexamethyldisilane as the starting material,which is cheap,non-toxic and commercially available,we have developed the highly chemo-and enantioselective palladium-catalyzed difunctionalization of unactivated alkenes by Heck/silanization sequence for the efficient synthesis of various chiral benzene-fused cyclic compounds bearing an trimethylsilyl all-carbon quaternary stereocenter(34 examples,31-99% yield,85-95% ee).In addition,the salient features include the use of readily available substrates,high selectivity,a broad substrate scope as well as versatile functionalizations of the products.