Organocatalytic Asymmetric Atroposelective Construction Of Axially Chiral Distyrene Compounds

Axial chiral compounds exist widely in natural products and have important bioactive activities.At the same time,axial chiral compounds are also an important source of chiral catalysts and ligand skeletons,which represent excellent prospective building blocks for chemical synthesis.Axially chiral styrene is a new species of atropoisomers.It has the potential applications in asymmetric synthesis as olefin ligands or organocatalysts.However,to date,only a few methods for asymmetric synthesis of axially chiral styrenes have been reported due to the relatively low-rotation energy to racemization.In addition,for the asymmetric construction of axially chiral styrene containing two axes was unreported.Therefore,according to the recently research progress of vinylidene o-quinone methide in our group,an efficient and mild synthetic method was developed for the construction of axial chiral distyrenes.Vinylidene o-quinone methide(VQM)contains high reactivity and multiple reaction sites,which can be generated through a prototropic rearrangement(tautomerization)of 2-(phenylethynyl)phenol under basic conditions.Recently,our research group disclosed an organocatalytic enantioselective approach for the construction of axially chiral sulfone-containing styrenes via intermolecular nucleophilic addition reaction.As part of an ongoing effort in our group to explore the application of VQM in asymmetric synthesis,in this article we designed a series of1,4-bis(phenylethynyl)-2,3-naphthalenes as VQM precursors in the presence of squaramide catalyst,the asymmetric nucleophilic addition reaction of in-situ generated VQMs with two equivalent of ?-amido sulfones as nucleophilic reagents afforded distyrene axial chiral compounds with double hydroxyl in the same plane.After a series of reaction condition screening,we obtained the distyrene axial chiral compounds with high yield and excellent stereoselectivity,and the reaction has wide substrate scope.Additionally,to further demonstrate the utility of the obtained chiral 1,4-distyrene2,3-naphthalene diols as organocatalysts or ligands,we investigated the obtained chiral1,4-distyrene 2,3-naphthalene diol(S,S)-3a as a ligand for the enantioselective addition of diethylzinc to naphthalene formaldehyde,the reaction was proceeded smoothly giving the chiral secondary alcohols with 27% ee value.The preliminary investigation indicated the potential of axially chiral 1,4-distyrene 2,3-naphthalene diols as ligands for asymmetric synthesis.