Study On The Synthesis Of α - Chiral Propargylamine And The Synthesis Of Chiral 2,4 - Disubstituted

1, Chiral amines are versatile building blocks in organic compounds. To date, asymmetric nucleophilic addition to imines constitutes an immensely useful strategy for the synthesis of chiral amines. N-terf-butanesulfinyl (t-BS hereafter) imines developed by Ellman can be widely used in synthesis of chiral 1,2-amino alcohol, diamines, (3-amino acids etc. Herein we report that the addition of alkynylmagnesium chloride to various t-BS imines proceed in a highly diastereoselective manner. Also from the propargylic adduct, we furnished the short asymmetric synthesis of (+)-Angustureine (3 steps,48% yield overall) and (-)-Cuspareine (4 steps,44% yield overall).2, Chiral 2,4-disub-piperidine structures exist in many drug moleculars. As the carbonyl group can be converted to many other groups, chiral 2-sub-4-piperidone severs as a good precursor in the synthesis of chiral 2,4-disub-piperidine. However, previous work in synthesis of chiral 2-sub-4-piperidone was especially limited by poor substrates range. Herein a new route to chiral 2-sub-4-piperidone was reported in which anion generated by lithium-iodine exchange attacking ester group intramolecular is a key step leading to the carbonyl group. Compared to previous work, a wide range of chiral 2-sub-4-piperidone can be synthesized with modest to high yields and high optical purity. Also, asymmetric synthesis of CGS 19755 is developed by this method.3, As a kind of unnatural amino acid, chiral 2-heterocycle glycine is mainly used in the research of pepitide. Existed reports only referred to synthesis of one kind of 2-heterocycle glycine. Herein we developed a general method in forming various chiral 2-heterocycle glycine, including 2-tetrahydrofuran,2-piperidine etc. SmI2 promoted asymmetric reductive coupling reaction between aldehyde and t-BS imine severs as the key step in constructing the chiral structure.