Primary Amines-Catalyzed Asymmetric Mannich Reaction And Friedel Crafts Alkylations Of Cyclic N-sulfonyl Trifluoromethyl Ketimines

Chiral primary amines are increasingly used in asymmetric synthesis as catalysts,which catalyzed reactions through the enamine or iminium intermediate transition states.Compared to secondary amine catalysts,N-H group on primary amines helps the formation of the reaction intermediates and stereoselectivity.Cyclic sulfonyl imines are an important class of heterocyclic compounds containing N,O,and S atoms in the ring.The asymmetric reactions of the sulfonyl imines allow the construction of chiral sultams.Trifluoromethyl functional group plays an important role in drug design and development,the asymmetric reaction of cylcic N-sulfonyl trifluoromethyl ketimines could provide a trifluoromethyl-containing sultam compounds containing four-dimensional stereogenic as the promising drug candidates.In this dissertation,the asymmetric Mannich and Friedel-Crafts reaction catalysted by primary amine have been studied using trifluoromethyl-substituted cyclic sulfonyl ketimine as substrates.1.Asymmetric direct Mannich reaction with methyl alkyl ketonesMannich reactions of cyclic N-sulfonyl trifluoromethyl ketimines with various methyl alkyl ketones were demonstrated.Through the screening of primary amine catalysts,co-catalyzed acids and solvents,it was found that under cocatalysis of a primary-tertiary amine derived from chiral 1,2-diphenylethylenediamine and trifluoroacetic acid,a series of trifluoromethyl-containing sulfamate compounds were obtained with up to 96%yield and 98%ee.The carbonyl group in the obained Mannich product was also transformated to chiral alcohol.2.Remote asymmetric Friedel-Crafts alkylation of 2-furylacetone through HOMO activationCatalytic asymmetric Friedel-Crafts alkylation is a powerful protocol for constructing a chiral C(sp2)-C(sp3)bond.Here presented the HOMO of the aromatic ? system of 2-furfuryl ketones is raised through the formation of a formal trienamine species using a chiral primary amine.Exclusive regioselective alkylation at the 5-position occurred with N-sulfonyl trifluoromethyl ketimines.Cyclic imine furan derivatives containing stereoisomeric trifluoromethyl groups are constructed,and high reactivity(98%yield)and moderate enantioselectivity(78%ee)are achieved by this remote activation.