Asymmetric Synthesis Of Chromanes、Sulfur-containing Azetidine And Pyrazolines

Since Anderson discovered the pyrrole; Scheele prepared furan, numerous heterocyclic compounds have been synthesized or discovered by chemists. Moreover, heterocyclic moieties can be found in almost all of the existing drug molecules and most of them are chiral. Therefore, it is higly demanded to develop efficient methodologies for the synthesis of chiral heterocyclic compounds. Among the strategies to obtain chiral compounds, asymmetric catalysis is the most efficient one and has being widely used in the construction of chiral heterocyclic compounds.In this thesis, the synthetic methods for three kinds of chiral heterocyclic compounds are described in detail in three parts:Part I: An asymmetric [3+2] reaction between Seyferth-Gilbert reagent and substituted chalcone was developed, and chiral pyrazoline derivatives were obtained. As we know, the cycloaddition reaction of Seyferth-Gilbert reagent with double bond always obtained nonchiral pyrazole; presumably because the pyrazoline intermediate is tend to be the more stable pyrazole through aromatization under alkaline conditions. In this part, pyrazolines were got by carefully selecting reaction conditions and substrate. A series of phosphoric acids derived from BINOL and SPINOL were designed and synthesized, which after coordinating with Ag2CO3 can catalyzed the desired reaction with highly selectivity and yield.Part II: An asymmetric three-component intermolecular asymmetric sulfa-Michael/Mannich cascade reaction of thiophenol, chalcones and imines catalyzed by chiral phase-transfer catalyst was designed. Under the catalytical condition, chiral acyclic sulfur containing compounds with multiple contiguous stereogenic centers were obtained in excellent diastereo- and enantioselectivities. Those products could be facilely transformed to the unprecedented chiral azetidine with four chiral centers via reduction and substitution reactions. This protocol provides simple method to complex sulfur-containing chiral compounds with potentially biological activities.Part III: An asymmetric oxa-Michael-aza-Henry domino reaction of 2-hydroxyaryl-substituted α-amido sulfones and nitroolefins for the synthesis of chiral trisubstituted chromanes was developed. With a series of bifunctional squaramides, chiral 4-amino-3-nitrochromanes were obtained with high yields and selectivities. These chiral 4-amino-3-nitrochromanes can be transferred to 3,4-diamino chromanes which have been shown to behave as good chiral ligands in the catalytic asymmetric transfer hydrogenation of acetophenone.