Optimization Of Synthesis Process And Application For Silicon-containing Pyrrolidine Derivatives

Proline derivatives are an important class of organic functional compounds that can be used in the fields of medicine,agriculture and chemistry.Because of the unique electronic effect of silicon groups,silicon-containing proline derivatives show great potential in application of asymmetric synthesis of intermediates and organocatalysts.However,the development of new chiral silicon-containing proline derivatives with high diastereomerism and enantioselectivity is still great challenge.At the same time,its application as a organic synthesis intermediates is still quite limited.In order to solve these research limitations,the following research works have been carried out:1.Synthesis process of proline derivatives was optimized and a large hindered silicon-containing group was introduced into the aza five-membered ring skeleton.Thereby,synthesis of a novel polychiral center silicon-containing proline derivatives were realized.In this process,we used copper-catalyzed [3+2] cycloaddition reaction of α,β-unsaturated acylsilane and Schiff base as a synthetic strategy,with the aid of Cu(I)/(R)-Xyl BINAP asymmetric catalytic system of organic compounds.The effects of reaction time,solvent,temperature and additives have been investigated one by one.Finally,an acylsilane substituted proline derivatives were obtained with high yields and excellent diastereomers(up to >98: 2 dr)and enantioselectivity(up to 98% ee).The process is mild,universal and suitable for the gram-scale preparation of the product.2.As an important synthetic building block,acylsilane-substituted proline derivatives(ASiP)have been further transformed into a variety of unnatural amino acid derivatives.Through desilylation,the application range of [3+2] cycloaddition has been extended to the enantioselective synthesis of amino acid derivatives with special structures,in which an unprecedented synergistic fluorinated anion promoted C-X(X = Si,N,C)bond is broken.ASiP can be converted into aldehyde-substituted pyrrolidine,linear cinnamaldehyde or olefin-substituted amino ester derivatives.It has a very high ee(90-98%),which can not be achieved by previously reported processes.In conclusion,the synthetic process of a new type of silicon-containing proline derivatives was optimized,and acylsilane-substituted proline derivatives were synthesized.By designing a “silicon introduction-departure-transformation” strategy,a preliminary exploration of the application value of ASiP has been made and a new type of unnatural amino acid library with diverse structures has been established successfully.It has important implications for the application of Silicon-Mediated Organic Synthetic chemistry and silicon-containing proline derivatives.