铜催化三取代环丙烯的 1,3-偶极环加成反应不对称构建具有五个连续手性中心的 3-氮杂双环[3.1.0]己烷骨架。
Asymmetric Construction of 3-Azabicyclo[3.1.0]hexane Skeleton with Five Contiguous Stereogenic Centers by Cu-Catalyzed 1,3-Dipolar Cycloaddition of Trisubstituted Cyclopropenes.
机构信息
School of Pharmacy and Shanghai Key Laboratory of New Drug Design , East China University of Science and Technology , 130 Meilong Road , Shanghai 200237 , China.
State Key Laboratory of Bio-Organic and Natural Products Chemistry Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry , University of Chinese Academy of Sciences , 345 Ling Ling Road , Shanghai 200032 , China.
出版信息
Org Lett. 2018 Jul 6;20(13):4121-4125. doi: 10.1021/acs.orglett.8b01686. Epub 2018 Jun 26.
A highly diastereo- and enantioselective desymmetrization of prochiral cyclopropenes via a Cu(CHCN)BF/Ph-Phosferrox complex catalyzed 1,3-dipolar cycloaddition of azomethine ylides was described. A variety of complex 3-azabicyclo[3.1.0]hexane derivatives bearing five contiguous stereogenic centers and two all-carbon quaternary stereogenic centers were directly synthesized as a single isomer in excellent yields (up to 99%) and enantioselectivities (97 → 99% ee). Notably, various functional groups (COR, CN, CONMe, and Ph) of cyclopropenes were found to be well-tolerated in this transformation. The cycloadduct was conveniently converted to a biologically important GABA derivative via LiAlH reduction and subsequent hydrolysis.
通过 Cu(CHCN)BF/Ph-Phosferrox 配合物催化的氮杂环丙烷亚胺叶立德的 1,3-偶极环加成反应，对前手性环丙烯进行了高非对映选择性和对映选择性的去对称化。各种复杂的 3-氮杂双环[3.1.0]己烷衍生物，具有五个连续的立体中心和两个全碳季碳立体中心，作为单一异构体以优异的收率（高达 99%）和对映选择性（97→99%ee）直接合成。值得注意的是，在这种转化中，环丙烯的各种官能团（COR、CN、CONMe 和 Ph）都能很好地耐受。通过 LiAlH 还原和随后的水解，环加成产物可方便地转化为具有生物重要性的 GABA 衍生物。
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