Three-component Reactions Catalyzed By Amino-appended β-cyclodextrins

Supramolecular catalysis is the catalytic mode closetst to enzyme catalysis. It was achieved through the host-guest interaction with macrocyclic host molecules. Cyclodextrins(CDs) are the second generation of supramolecular hosts which possess virtues of molecular recognition and self-assembly. (3-CD is the most popular one among CD family due to its readiest availability. However, the catalytic performance of β-CD has been restricted by its poor water solubility and functional homogeneity. Chemical modification of P-CD provides a useful option for addressing this issue. Inspired by the robust aminocatalysis, we designed to fabricate amino group-modifiedβ-CDs to combine supramolecular catalysis and aminocatalysis. Six amino-appended β-cyclodextrins (ACDs, a0-5), were prepared and applied to catalytic three-component reactions, the structure-activity relationship between the structure of catalyst and reaction results was obtained and the catalytic mechanisms were elucidated in detail with 1D and 2D NMR ESI-MS analyses and job plot, while the key role of amino side chains of ACDs in the chemoselectivity was addressed for the first time.The main contents of this work are as follows:Firstly, four ACDs(a0-3) were synthesized and used to catalyze the three-component synthesis of tetraketones.1. The catalyst screening and the optimization of reaction conditions were performed with benzaldehyde and dimedone in water at room temperature.2. The substrate scope was explored. Yields of 58－97%　were obtained with up to 30 examples of substrate.3. The reaction mechanism was extensively studied by H-NMR. and 2D-NMR, HR-MS and Job’s plot.4. The catalyst efficiency was evaluated through catalyst recycling and recovery experiment. The catalyst could be recycled easily, while a 92% yield and 84% rate of catalyst recovery could be achieved after 8 cycles of catalyst recycling.This protocol retained the promising advantages of ambient temperature, green medium, simple operation, broad substrate scope, excellent yields and superb catalyst recycling performance.Secondly, six ACDs(a0-5) were synthesized and used to catalyze the three-component synthesis of 2-amino-4H-chromenes.1. The catalyst screening and the optimization of reaction conditions were performed with benzaldehyde, malononitrile and resorcinol in water at room temperature.2. The substrate scope was explored. Yields of 82-95% were obtained with up to 32 examples of substrate.3. The catalytic mechanism was elucidated in detail with 1D,2D NMR and ESI-MS analyses.An efficient one-pot three-component synthesis of 2-amino-4H-chromenes was established by supramolecular catalysis with ACDs in water. A detailed study of the catalytic mechanism was conducted, which suggested a combination of supramolecular catalysis and covalent catalysis, and also indicated the key roles of amino side chains in the newly detected chemoselectivity in this reaction.In this paper, a series of amino-modified β-cyclodextrin catalyst were we designed and synthesized. Its catalytic role was studied through the three-component reaction. The mechanism of the chemical selectivity that ACDs produced in the multi-component reaction was revealed for the first, which could provide a new idea for the constructing of the supramolecular body/organic catalytic system.