Synthesis Of Atropisomers With Biaryl And Vinylaryl Chirality Via Pd-catalyzed Ring-opening Reaction

This thesis mainly studied the Pd-catalyzed ring-opening reaction of chiral 8Hindene[1,2-c]thiophene-8-ols by using achiral ligands.Through center-to-axis chiral transfer,we synthesized diaxial atropisomers with both biaryl and vinylaryl chirality.The contents mainly includes the following two chapters:In the first chapter,we summarize the strategies and research progress for the construction of biaryls atropisomers,axially chiral styrenes,and multiple axes compounds.The less rigid structure of vinylarenes in comparison with biaryls leads to the lower rotational energy barrier and difficulty in synthesis of axially chiral styrenes,the construction methods of axially chiral styrene have only been developed in recent years,such as C-H functionalization,asymmetric Michael addition,or cycloaddition.While the study of vinylidenen ortho-quinone methide(VQM)intermediates provided the new synthesis strategy.The existing methods for constructing polyaxially chiral compounds also mostly lie in polyaxial biaryl axis chiral compounds.The construction methods for multiple axes biaryls.The strategies generally include the following:constructing two or more axes through cycloaddition reactions;The introduction of stereoaxes through multiple areneforming reaction or continuous dynamic kinetic resolution,and the construction of two aryl-vinyl axes through VQM intermediates.The second part of the thesis mainly introduced a palladium-catalyzed domino cyclization/ring-opening reaction between 8H-indeno[1,2-c]thiophen-8-ols and N-(2bromophenyl)propiolamide derivatives.The reaction features a highly stereospecific point chirality to axial chirality transfer process,which enables the synthesis of molecules containing two chiral axes from the compounds with only one stereogenic center.In these reactions,the sterically bulky vinyl palladium species formed in situ efficiently reacted with the sodium alkoxide to form one aryl-aryl chiral axis and one vinyl-aryl chiral axis.This demonstrated a practical example showing that multiple types of axial chirality could be constructed via a chirality transfer process from a single-carbon stereogenic center.We screened the achiral phosphine ligands to get the optimal ring opening conditions,and modified the structure of the alcohol and propanamide derivatives to expand the substrate.The existence of vinyl-aryl chiral axis was also demonstrated through density functional theory calculations and control experiments.