Prolinol Thio-Ethers As Organocatalysts For Asymmetric Reactions

In this thesis, the recent advances in the asymmetric organocatalysis and especially in proline and its derivants catalyzed enantioselevtive reactions were summarized and reviewed. Then, novel classes of prolinol thio-ethers were extensively studied on their design, preparation and properties in asymmetric non-solvent Michael reaction, asymmetric Diels-Alder reaction in water, supramolecular catalyst on asymmetric Diels-Alder reaction and its constructed self-assembly system on asymmetric cascade oxa-Michael-Mannich reaction. This dissertation include the following five parts:(1) Some general examples of organocatalysis were reviewed. Especially, the enantioselevtive Mannich, Michael and Diels-Alder reactions, catalyzed by proline and its derivants via enamine catalysis or iminium catalysis, were introduced in details. And the novel prolinol thio-ethers were designed and synthesized. (2) The study demonstrated that the novel organocatalytic system, consisting of the designed (S)-2-(pyrrolidin-2-ylmethylthio)-pyridine and4-trifluoromethyl-benzoic acid, presented excellent asymmetric induction properties in the asymmetric non-solvent Michael reactions of ketones to y-substituted nitrodienes. Michael adducts were afforded with good to high yields (up to99%), good to excellent diastereoselectivities (dr up to>99:1) and excellent enantioselectivities (up to>99%ee).(3) The study demonstrated that the Diels-Alder reactions, nitroolefins reacted with cyclohexenones smoothly, catalyzed by the system of (S)-2-(pyrrolidin-2-ylmethylthio)-pyridine and4-trifluoromethyl-benzoic acid, to give the desired adducts in high yields (up to99%) with excellent diastereoselectivities (exo/endo up to25:1) and excellent enantioselectivities (up to96%) in brine. Further study confirmed that the Diels-Alder reaction followed in situ enamine-activated mechanism.(4) The study demonstrated that a new kind of chiral supramolecular organocatalyst, self-assembed by PEG or PPG with prolinol thio-ethers through noncovalent interactions, was disclosed. Furthermore, highly efficient asymmetric organocatalytic performance was shown in Diels-Alder reactions between cycloenones and nitrodienes with high yields (up to99%), excellent diastereoselectivities (exo/endo>25:1) and excellent enantioselectivities (up to99%) by the devising supramolecular catalyst.(5) The study demonstrated that the catalytic property of the self-assembly system of (S)-2-(pyrrolidin-2-ylmethylthio)-pyridine and D-tertiary leucine on the reaction of enones with salicylic aldehyde was studied. The versatile tetrahydroxanthenones adducts were afforded with high yields (up to95%) and excellent enantioselectivities (up to98%ee) with R configuration via dual activated tandem oxa-Michael-Mannich reaction mechanism.And moreover, the mechanism of the asymmetric reaction and the formation of the chiral supramolecular catalyst were all further confirmed by the ESI-MS、HRMS、NMR methods.