Nickel/Spiroindenylphosphineoxazoline Catalyzed Asymmetric Arylation Of Arylboronic Acid To Benzosulfonimide

Benzosulfonamide are an important motif present in many natural products,biologically active compounds and functional organic molecules.Benzosulfonamide is considered as an inhibitor and is used in the field of antibacterial and antiviral drugs.In addition,benzosulfonamides are also widely used in the field of organic synthesis as chiral and fluorinated reagents.The asymmetric addition of imines catalyzed by transition metals is the most direct and effective method to obtain benzosulfonamide.The asymmetric addition reaction of arylboronic acid to benzosulfonimide was catalyzed by expensive rhodium or palladium to give chiral amines with higher enantioselectivity and yield.In this paper,we synthesized a rigid spiro indanyl phosphine–oxazoline ligand based on the analysis of the structure of metal complexes.We used cheaper metal and explored nickel catalyzed enantioselective addition of arylboronic acids to cyclic benzosulfonimides.The rigid spiro indanyl phosphine–oxazoline ligands L1-L3 were synthesized from available 7-bromo-1-indanone by condensation,streker reaction,hydrolysis,oxidation,reduction,cyclization and substitution.The optical purity of the ligands were determined to be 100% by HPLC.The ligands L1-L3 have the advantages of strong rigidity.The oxazoline structure of the spirophosphine-oxazoline ligand is directly connected to the indane structure through the spiro carbon.The metal is difficult to rotate when coordinated with P and N atoms,which is conducive to the improvement of enantioselectivity in asymmetric catalysis.The chiral center of ligand is obtained through chiral induction,which effectively avoids resolution.At the same time,the ligand contains only one chiral center,which is conducive to the asymmetric catalytic reaction.Nickel-spirophosphine-oxazoline ligands SMI-PHOX were examined for enantioselective addition of arylboronic acids to cyclic N-sulfonyl imines.By exploring the effects of solvent,temperature,ligand substituents and metal,the optimal conditions for asymmetric arylation were determined.Under the optimal conditions,the substrate adaptation range was studied.The asymmetric arylation reaction could afford 36 target chiral benzosulfonamides in high yields(up to 98%)and enantioselectivities(up to 99%).It was found that enantioselectivities obtained from arylboronic acids with electron-withdrawing substituents were higher than electron-donating substituents.Fused-ring aryl and disubstituted arylboronic acids could also afford their corresponding products with high yields and excellent enantioselectivities.When the substrates were six-membered ring N-sulfonyl imines,the enantioselectivities were slightly lower than that of the five-membered ring N-sulfonyl imines.Enantioselectivities obtained from arylboronic acids with electron-withdrawing substituents were higher than electron-donating substituents.Heteroaryl and disubstituted boronic acids could give their corresponding products with good yields and enantioselectivities.Arylboronic acid with a much bulkier group also gave corresponding product,but the enantioselectivity is relatively poor.Furthermore,N-sulfonyl ketimines could give small amounts of the products with good enantioselectivities.The configurations of products were determined by HPLC and optical rotation of the product.Based on this,the transition state model of ligands and nickel complexes in the asymmetric arylation reaction was analyzed.Chiral benzosulfonamides in high yields and enantioselectivities were obtained by nickel catalyzed enantioselective addition of arylboronic acids to cyclic benzosulfonimides.This method provides a new and effective way to obtain chiral benzosulfonamides.