Palladium-Catalyzed Diastereo-and Enantioselective [3+2] Cycloaddition Of Vinylcyclopropanes With Azadienes

Benzofuran and related substrates are widely found in a variety of natural products.This prevalent framework is of biological activities and already used in drug design.A few of strategies for construction of spiro-compounds already have been reported,among which the intermolecular cycloaddition reaction seems more economical and efficient.At first,we introduced the intermolecular cycloaddition reactions of VCPs or BDAs briefly.Activated vinylcyclopropanes which are activated by attaching electron-withdrawing groups and vinyl group to the cyclopropanes have been widely used in the metal-catalyzed cycloaddition reactions.A diverse range of cycloaddition reactions of VCPs with activated alkene,imine,ketone,aldehyde or diazonium have been achieved under the palladium catalyst.Additionally,another strategy involves using Lewis acid as the catalyst.Under the Lewis acid,a variety of cycloadditions between VCPs and electron-rich olefins,imine,ketone,aldehyde as well as 1,3-dipole were reported.Meanwhile,the asymmetric cycloaddition reaction of VCPs is achieved using chiral ligand or other conditions under these catalysts.Besides benzofuran-derived azadienes(BDAs)have emerged as four-atom synthon for[4+n]cycloadditions due to strong driving force of aromatization,while taking BDAs as two-atom synthon underdeveloped.In the paper,we have completed the palladium-catalyzed asymmetric[3+2]cyclization of VCPs and BDAs to access the chiral spiro[benzofuran-cyclopentane]derivates with multi-chiral centers containing a quaternary carbon chiral center.This is the first asymmetric cyclization reported involving BDAs as a two-atom building block.A broad scope of cycloadducts(31 examples)were furnished under mild conditions in good yields with excellent diastereo-and enantioselectivities(up to 93%yield,>20:1 dr,>99%ee).To demonstrate the synthetic utility,the reaction was enlarged to 1 mmol scale with reduced loading of palladium catalyst,providing cycloaddition products with yield and stereoselectivities unchanged.Furthermore,a series of polycyclic substrates,such as tricyclo-[8.3.0.01,5]-azepines and tricyclo-[7.3.0.01,5]-piperidines,transformed from functionalized spirocyclic product 125aa were reported,providing an efficient method for the synthesis of structurally complex benzofuran derivates.