Copper(I)-Catalyzed Stereodivergent Propargylation of N-Acetyl Mannosamine for Protecting Group Minimal Synthesis of C3-Substituted Sialic Acids
Copper(I)-Catalyzed Stereodivergent Propargylation of N-Acetyl Mannosamine for Protecting Group Minimal Synthesis of C3-Substituted Sialic Acids
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DOI：
10.1021/acs.joc.9b00887
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发表时间：
2019-09-06
影响因子：
3.6
通讯作者：
Kanai, Motomu
中科院分区：
文献类型：
--
作者：
Ishizawa, Kouhei;Majima, Sohei;Kanai, Motomu
以3-取代丙二烯基硼酸酯为亲核试剂，研究了铜（I）催化的N-乙酰甘露糖胺异头碳上的亲核炔丙基化反应。高炔丙醇产物含有两个连续的立体中心，并且通过应用碱性条件：具有B（OiPr）（3）添加剂的MesCu/（R，R，R）-Ph-SKP催化剂或酸性条件：具有Me B（OiPr）（2）添加剂的CuBF 4/（S，S，S）-Ph-SKP催化剂，以催化剂控制的方式选择性地获得四种可能的异构体中的两种立体异构体。机理研究表明，存在不同的活性亲核物种取决于条件：一个allenylcopper物种在碱性条件下或allenylboronate活化的刘易斯酸性铜催化剂在酸性条件下。炔丙基化产物在不使用保护基的情况下在两个步骤中简明地转化为C3-取代的唾液酸。
Copper(I)-catalyzed stereodivergent nucleophilic propargylation at the anomeric carbon of unprotected N-acetyl mannosamine was developed using 3-substituted allenylboronates as a nucleophile. The homopropargylic alcohol products contained two contiguous stereocenters, and two stereoisomers out of the four possible isomers were selectively obtained in a catalyst-controlled manner by applying either basic conditions: a MesCu/(R,R,R)-Ph-SKP catalyst with a B(OiPr)(3) additive or acidic conditions: a CuBF4/(S,S,S)-Ph-SKP catalyst with an MeB(OiPr)(2) additive. Mechanistic studies suggested the presence of distinct active nucleophilic species depending on the conditions: an allenylcopper species under the basic conditions or an allenylboronate activated by the Lewis acidic copper catalyst under the acidic conditions. The propargylation products were concisely transformed into C3-substituted sialic acids in two steps without the use of protecting groups.