Nucleophilic Addition Reaction Of Cyclic N-sulfonyl α-ketiminoesters

The Lewis acids catalyzed reaction of N-sulfonyl ketimines is an efficient and direct method for synthesis of benzosultams,which are widely present in a large number of natural products and have good biological activity and can be used as a useful chiral auxiliary in some asymmetric transformations.The addition reaction of nickel-catalyzed cyclic N-sulfonyl α-ketiminoesters with terminal alkynes or 2-methy azaarenes was studied and developed.By these method,a series of alkyne-substituted or 2-methy azaarenes-substituted benzosultams compound can be obtained in high yields.The terminal alkynes as a nucleophile to react with cyclic N-sulfonyl α-ketiminoesters.After the systematic optimization of reaction condition through solvent screening,investigation of chrial ligands,examination of temperature and so on,the optimal condition was defined as: Nickel(II)perchlorate hexahydrate as catalyst,(R)-DTMB-SEGPHOS as chiral ligand,the asymmetric addition reaction proceeded efficiently in dichloromethane.The reaction affords 27 examples of chiral propargylic amine bearing C3-quaternary stereocenters centers in modest to good yields(44-84%)with excellent enantioselectivities(80-97% ee).Theoretical studies revealed that this reaction proceeded via a Friedel-Crafts-type reaction pathway.The 2-methy azaarenes as a nucleophile to react with cyclic N-sulfonyl α-ketiminoesters.After the systematic optimization of reaction condition through solvent screening,investigation of catalysts,examination of temperature and so on,the optimal condition was defined as: Nickel(II)perchlorate hexahydrate as catalyst,1,10-phenanthroline as ligand,the addition reaction proceeded efficiently in tetrahydrofuran.The reaction affords 14 examples of benzosultams bearing 3-membered 2-methy azaarenes-substituted in modest to good yields(63-90%).