Chiral Amines Catalyzed Asymmetric Domino Reactions

Organocatalysis has been developed as a powerful tool for the preparation of enantiomerically pure compounds in the past decade. Especially the chiral amines catalyzed asymmetric domino reactions has been intensively researched and become the hot topic in organic chemistry. In this dissertation, recent advances in the chiral amine catalyzed enantioselevtive domino reactions were summarized and reviewed according their catalytic mechanism modes firstly. Then, chiral amines catalyzed domino thio-Michael/Aldol/Dehydration reaction and domino thio-Michael/Aldol/Dehydration reaction were presented.A novel powerful enantioselective domino thia-Michael/aldol/dehydration reaction has developed to synthesize functionalized chiral dihydrothiophenes from readily available starting materials ofα,β-unsaturated aldehydes and 1, 4-dithiane-2, 5-diol. The study demonstrated that in the catalytic system of (S)-2-(diphenyl(trimethylsilyloxy)methyl)pyrrolidine (20 mol%) and 4-nitrobenzoic acid (10 mol%),α,β-unsaturated aldehydes could react with 1,4-dithiane-2,5-diol smoothly to give the products in high yield (up to 90%) and with excellent enantioselectivity (up to >99% ee) at room temperature in toluene. To the best of our knowledge, this is the first example of highly enantioselective synthesis of functionalized dihydrothiophenes catalyzed by a secondary amine. Based on the experimental results and APCI mass spectrometric detection of the intermediates, a plausible transition state has been proposed to explain the domino process.In the following study , the asymmetric domino thio-Michael/Henry/Dehydration reaction of nitroolefins with 1,4-dithiane-2,5-diol catalyzed by Chiral Squaramide, which is synthersize from quinine, with the additive of (L)-Proline was presented and give the adducts with up to 55% yield and 47% enantioselectivity in THF at room temperature.In conclusion, two different kind of asymmetric domino reactions were presented and realized the asymmetric synthesis of chiral dihydrothiophenes, which are valuable intermediates due to their versatile modifiability.