Palladium-Catalyzed Enantioselective Tandem Heck/Tsuji-Trost Reaction

Palladium-catalyzed tandem asymmetric Heck/Tsuji-Trost reaction of 1,n-dienes is an efficient strategy for the construction of complex chiral molecules from simple starting materials.In recent decades,a number of palladium-catalyzed cascade asymmetric difunctionalizations of allenes and 1,3-dienes proceeding through a Heck/Tsuji-Trost process have been developed.However,successful examples involving 1,4-dienes are relatively rare,due to the challenge in simultaneously controlling the regioselectivity and stereoselectivity.This thesis describes the first asymmetric Heck/Tsuji-Trost reaction involving 1,4-dienes.We have established a chiral Pd complex-catalyzed asymmetric coupling of 2,5-cyclohexadienyl-substituted aryl iodides with carbon or heteroatom nucleophiles,furnishing the optically active tetrahydrofluorenes containing three chiral centers as single diastereoisomers in moderate to high yields and with excellent enantioselectivities.The reaction proceeds via a Pd-catalyzed tandem intramolecular desymmetrizing Heck insertion and allylic alkylation,oxygenation or amination,capable of tolerating a broad scope of substrates.In the reaction,the choice of a H8-BINOL-derived phosphoramidite ligand bearing electron-withdrawing substituents is crucial for successful catalysis,which not only enhances the catalytic activity but also provides an appropriate chiral environment for asymmetric induction.Moreover,the reaction could be conducted in gram-scale,and the products could be readily converted to various useful derivatives.