Construction Of Spirooxindoles By Asymmetric Intramolecular [3+2] Cycloaddition

Spirocyclic compounds have been a hot topic in the field of organic synthesis.Spiroxyindole,as a special spiral ring structure,is of great significance in modern organic chemistry,medicine and natural products because it exists widely in many natural products and biologically active molecules.In the past decade,many enantioselective catalytic strategies have been developed for the construction of spiro[pyrrolidine-2,3-oxindole] skeleton.However,the diversity of the corresponding compounds constructed by these strategies is still insufficient,and the structure of the products is relatively simple.Because the structural diversity determines the performance diversity,it is of great significance to develop new and efficient synthesis strategies to construct such structures.On the other hand,as an important oxygen-containing heterocyclic compound,chromane has great application value in the field of pharmacochemistry and organic chemistry.Considering the important application of chiral molecules in pharmaceutical chemistry and the advantages of 1,3-dipolar cycloaddition,such as high simplicity of steps,atom economy and controllability of chirality,etc.We hope to design the substrates reasonably:With 3-aminohydroxyindole and o-allyloxybenzaldehyde as substrates,they first condense to form a 1,3-dipole,and then undergo an asymmetric intramolecular [3+2] cyclization under the promotion of chiral catalysts.Thus,the highly colorful spiro [pyrrolidine-2,3-hydroxyindole]compounds can be efficiently constructed by one-pot method.The specific work is as follows:In this paper,an efficient and highly complex asymmetric synthesis strategy was developed.With 3-aminohydroindole hydrochloride and o-allyloxybenzaldehyde as substrates,methylimine ylide was synthesized in situ under the promotion of chiral catalysts,and then the intramolecular asymmetric [3+2] cycloaddition reaction took place to construct spiro heterocycles and fused heterocycles,thus forming complex and enantioselective spiro[pyrrolidine-2,3-hydroxyindole] compounds.After investigating the factors affecting the reaction,such as catalyst,solvent,alkali,molecular sieve and so on,we determined the optimum reaction conditions,and obtained 1,3-dipolar cycloaddition products with excellent yield,non-enantioselectivity and good enantioselectivity.