Chemical Transformations Of The Carbon-Nitrogen Bonds Of Imines And Alkylamine Derivatives Under Acidic Conditions

Carbon-nitrogen bonds are chemically inert and exist in many organic molecules. Although some methods have been developed for the cleavage of carbon-nitrogen bonds with metals, strong acids, or bases, they are not suitable for the development of highly selective organic reactions because of harsh reaction conditions. We have employed appropriate electron-withdrawing groups and acidic catalysts to activate carbon-nitrogen bonds, and developed some coupling and annulation reactions of imines and alkylamine derivatives with nucleophiles through carbon-nitrogen bond cleavage. Our studies have demonstrated that carbon-nitrogen bond cleavage can be utilized to form new carbon-carbon and carbon-heteroatom bonds.Catalytic selective bi-arylation of N-tosyl imine with anisole, phenol, thioanisole and analogues has been developed to give the corresponding triarylmethanes or diarylmethanes with high regioselectivity in good to excellent yields. Various N-tosyl aromatic imines N-tosyl aliphatic imines could participate the reaction to give the corresponding triarylmethanes or diarylmethanes in the presence of Bi₂(SO₄)₃ and TMSCl at room temperature.Selective alkylation of protic nucleophiles with N-alkylsulfonamides has been developed. A broad range of tosyl-activated benzylic and allylic amines couple with active methylene compounds, aromatics, thiols, and thioacetic acid to give diversely functionalized products in good to excellent yields and with high regioselectivity in the presence of ZnCl₂ and TMSCl at room temperature. Stereochemistry study suggests that carbocations are generated as intermediates in these reactions. Furthermore, the cross-coupling reaction of 1,3-dicarbonyl compounds with benzylic propargylic amine derivatives has been successfully applied to the one-step synthesis of polysubstituted furans and benzofurans.Catalyst-free alkylation of N–alkylsulfonamides with sulfinic acids has been developed at room temperature to give structurally diversified benzylic and allylic sulfons. Further study suggests that N-(2-acetyl)allylic sulfonamides couple with sulfinic acid in an SN2'-type process to give the corresponding trisubstituted allylic sulfons with Z selectivity. The reaction of N-benzylic sulfonamides with ankynes have been investigated under various reaction conditions. In the presence of FeCl₃, the [3+2] annulation of N-benzylic sulfonamides with internal alkynes, alkynylcarbonyl compounds, alkynyl halides, or alkynyl chalcogenides proceeds smoothly to give various functionalized indene derivatives with extremely high regioselectivity. Nevertheless, N-benzylic sulfonmides couple with terminal alkynes to give the corresponding internal alkynes in the presence of TfOH and Fe(OTf)₃.