Study On Several In-situ Generated Ketenimine Participated Reactions

Since the strategy for the generatation of ketenimine via the copper-catalyzes alkyne-azide cycloaddition (CuAAC) was reported by Chang in 2005, the ketenimine chemistry has emerged as a powerful tool in organic chemistry. On the basis of CuAAC reaction, we signeted and developed several cascade or multi-component reactions, which involved the in situ generated ketenimine intermediates. The details are summarized as following:1. We developed an efficient method for the preparation of dihydropyrimidin-4-ones from N-(prop-2-yn-l-yl)amides and sulfonyl azides. The cascade reaction underwent copper-catalyzed alkyne-azide cycloaddition, formation and intramolecular nucleophilic addition of ketenimine, and subsequent rearrangement in a single step. Moreover, the starting materials, propargylamides, could be easily prepared from propargylic alcohols via Ritter reaction or from propargylamines via aminolysis of acid chlorides, While sulfonylazides could be obtained from sulfonylchlorides and sodium azid With the diverse pharmacological activities of dihydropyrimidinones, our method shall find its applications in medicinal chemistry.2. An efficient method to synthesis 3-amino-2-carbamimidoylacrylamides from sulfonyl azides, propriolamides, and amidines with copper-catalyzed was developed. Lots of substituents tolerated the reaction conditions and provided 3-amino-2-carbamimidoylacrylamides in moderate to good yields. A cascade mechanism was proposed that included copper-catalyzed alkyne-azide cycloaddition (CuAAC), ring-opening of N-tosyl-1,4-disubstituted-1,2,3-triazole, Dimorth rearrangement, and [2+2] cycloaddition of ketenimine and amidine, and a subsequent ring opening of azetidine. By analyzing the crystal structures of 3-amino-2-carbamimidoylacrylamides, three crystal systems were observed. Two of them were triclinic with the space group of P-1 and existed as dimers viaintermolecular hydrogen-bonding. One was monoclinic with the space group of P21/C and existed as a linear structure via intermolecular hydrogen bonding. Although the same space groups (P21/C) were observed for other two structuers, these crystal structures lost intramolecular π...π stacking and created channels for the complexation with the guest of ethyl acetate via the weak intermolecular C-H...π and π...π interactions van der Waals forces.3. We developed an efficient method for the preparation of multifunctionaled (1E, 2E)-acrylimidamide from 2-yn-1-yl acetate, sulfonyl azides and aniline. The cascade reaction underwent copper-catalyzed alkyne-azide cycloaddition and Dimorth rearrangement, the moleculer of ketenimine was attacked by amiline and lost the levea group of acetate, to give (1E,2E)-acrylimidamide. The oxidative C-H amination of N-aryl-N’-sulfonylamidines has been accomplished using iodobenzene as a catalyst to furnish functionaled 2-styryl-l-tosyl-lH-benzo[d]imidazoles in the presence of mCPBA as a terminal oxidant at room temperature.