Asymmetric Organocatalytic Synthesis Of Chromans,Dihydrocoumarins And Sulfur-Containing Heterocyclic Compounds

para-Quinone methides(p-QMs)are an important quinone derivatives,which are widely found in natural products and organic molecules with biological activities.And they are also the key intermediates in many chemical reactions,biosynthesis and drug metabolism.p-QMs have a unique bisvinylogous enone system and consist of a cyclohexadiene moiety in para-conjugation with a carbonyl group and an exo-methylene component.The polarization of carbonyl group and the tendency to aromatization make it electrophilic.Although the asymmetric organocatalysis of p-QMs have been widely studied in organic chemistry in the past few years,its substrate range is still limited.Our research group continued the research on p-QMs,and selected three nucleophiles,such as malononitrile,azlactones and 5H-thiazol-4-ones.With the help of organic catalysts,we have successfully synthesized some chromans,dihydrocoumarin derivatives and sulfur-containing heterocyclic compounds with high efficiency and high stereoselectivity.Part Ⅰ: This work designs and implements a bifunctional squadramide catalyzed asymmetric domino reaction of p-QMs with malononitrile.Firstly,the feasibility of the scheme was confirmed by the template substrate.Subsequently,we optimized the reaction conditions,and selected the chiral catalysts,the solvents,the amount of solvent,temperature and amount of catalysts.Finally,we obtain the optimized conditions that can maximize the stereoselectivity and yield of the product.The method has good applicability for different substituted p-QMs.The yield of the obtained products was 71-99% and ee value was 86-96%.By this method,we successfully synthesized a series of chiral chromenes with high enantioselectivity.At the same time,this report provides a new efficient and simple method for the synthesis of 2-amino-4H-chromenes.Part Ⅱ: This work was designed to achieve the asymmetric organocatalytic Diels-Alder reaction of p-QMs with azlactones catalyzed by chiral phosphoric acid.Firstly,the feasibility of the scheme was confirmed by using template substrate.Subsequently,the reaction conditions were optimized,and the chiral catalysts,the type of solvent,the amount of solvent,the ratio of reactants and the amount of catalyst were screened in turn.Finally,we obtain the optimized conditions that can maximize the stereoselectivity and the yield of the product.This method is also suitable for the synthesis of a series of chiral dihydrocoumarins with high yield(72-98%)and stereoselectivity(64-98% ee,>20:1 dr).At the same time,this report provides a new efficient and simple method for the synthesis of various chiral dihydrocoumarin derivatives bearing a quaternary amino acid moiety.Part Ⅲ: This work designed a catalyst-controlled diastereodivergent conjugate addition of p-QMs to 5H-thiazol-4-ones.We use the same reactant to achieve the reaction by establishing two catalytic systems of chiral squadramide and chiral phosphoric acid.Then,the optimized conditions were determined by the selection of catalysts,solvents and the amount of catalyst.Under this condition,the universality of substrates was explored,and two groups of diastereomers were finally synthesized with high yield(76-97%)and excellent asymmetric selectivity(78->99% ee,up to >20:1 dr).At the same time,this report provides a new efficient and simple method for the synthesis of sulfur-containing heterocyclic compounds with adjacent chiral centers.