Preparation Of Trifluoromethyl-Substituted ?-sultams And Their Stereoselectivity

Both trifluoromethyl and ?-sultam are important groups and structural motifs in medicinal chemistry.P-Sultams are considered as important structural alternatives to solve the resistance of ?-lactam antibiotics.Therefore,compounds containing both trifluoromethyl and ?-sultam structures should be potential prodrugs,and no synthetic methods for them have been reported till now.Preparation methods of sulfonyl chlorides were reviewed and simple,environment-friendly,and laboratory-useful methods were introduced in details in this dissertation.The synthetic methods of ?-sultams and the introduction methods of the trifluoromethyl group into(3-lactams were also reviewed.2,2,2-Trifluoroethylsulfonyl chloride and various imines were prepared by referring previously developed methods in our research group.Various 4-trifluoromethyl-?-sultams were successfully prepared from 2,2,2-trifluoroethylsulfonyl chloride with imines via sulfa-Staudinger cycloaddition.Under mild conditions,the direct reactions of 2,2,2-trifluoro ethylsulfonyl chloride and two equivalents of different imines afforded a series of structurally different 4-trifluoromethyl-?-sultams via the sulfa-Staudinger cycloaddition under stirring.The yields of the products are up to 75%and the cis/trans ratios range from 12:78 to 59:41.In addition,the stereoselectivity of the reactions and the stereochemistry of the products were investigated.The annuloselectivity and the stereochemistry of annuladducts in the reaction of 2,2,2-trifluoroethylsulfonyl chloride and cyclic imine 3,4-dihydroisoquinoline were also studied.The annuloselectivity in the reactions of 2,2,2-trifluoroethylsulfonyl chloride and imines was discussed and summarized.(1)2,2,2-Trifluoroethylsulfon chloride and linear imines only undergo the sulfa-Staudinger cycloaddition,affording 4-trifluoromethyl-?-sultams.(2)2,2,2-Trifluoroethylsulfon chloride and cyclic imine 3,4-dihydroisoquinoline undergo the[2+2+2]annulation to give rise to two pairs of six-membered ring annulated products.Reasonable reaction mechanisms on[2+2]and[2+2+2]annulations were proposed on the basis of chemistry of annulated products.The current method provides a simple method for the synthesis of 4-trifluoromethyl-?-sultam core skeleton,and also reveals the annulo-and stereoselectivites and stereochemistry of products in reactions of 2,2,2-trifluoroethylsulfonyl chloride with imines.It provides a simple and effective synthetic method for related drug researchers and will provide a guide for the relevant work.