Chiral Naphthyl-C2-indole As Scaffold For Phosphine Organocatalysis: Application In Asymmetric Formal [4+2] Cycloaddition Reactions

Asymmetric catalysis is one of the most efficient methods for the synthesis of optically active compounds and the key to improve the reactivity and stereoselectivity is the catalyst.Therefore,the development of highly efficient chiral catalysts has been one of the central themes in the field of asymmetric catalysis.Chiral phosphine organocatalysis has evolved into a powerful and reliable tool for the construction of diverse chiral molecular frameworks.Numerous reactions have been innovatively developed to provide multiple paths towards numerous chiral adducts.In particular,chiral phosphine catalyst bearing a phenolic hydroxyl group has gained much attention due to its Lewis base and Br（？）nsted acid properties,which can stabilize the key active intermediate through hydrogen bonding interactions,thus giving rising to products in good yields with excellent stereoselectivities.To date,backbones used in such catalysts were mostly C₂-symmetric scaffolds such as BINOL and SPINOL,while the non-symmetric scaffolds were rarely investigated.Indole is an ideal candidate for application as chiral organocatalysts or ligands core skeleton due to its unique chemical structure and properties.However,compared to the well-established preparation of six-membered biaryl atropisomers,the construction of five-membered species is still a challenge in modern asymmetric synthesis.This is due to the fact that the increased distance between ortho-substituents adjacent to the axis dramatically reduces the conformational stability,which makes racemization easy to take place.In addition,due to the limitation of further functionalization,it is difficult to install the catalytic active centers,which makes their application as chiral organocatalysts or ligands less studied.In this study,combining with the recently research progress of vinylidene ortho-quinone methides（VQMs）in our group,chiral naphthyl-C2-indole skeleton was introduced to bifuctional phosphine organocatalysis for the first time and the excellent stereocontrol was achieved in two cases of formal[4+2]cycloaddition reactions.With the optimal reaction condition,a series of chiral spirooxindole and hydrodibenzofuran architectures were produced in moderate to good yields with excellent stereoselectivities.In the above two reactions,the naphthyl-C2-indole bifunctional tertiary phosphine catalyst showed excellent catalytic activity,chiral induce ability and broad substrate scope.Moreover,the core skeleton of the catalyst is innovative and can be modified with multiple functional groups,thus is expected to be used as the"privileged framework"in more asymmetric catalytic reactions.