Anionic additions to glycosyl iodides: Highly stereoselective syntheses of beta-, C-, N-, and O-glycosides
Anionic additions to glycosyl iodides: Highly stereoselective syntheses of beta-, C-, N-, and O-glycosides
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DOI：
10.1021/jo970922t
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发表时间：
1997-10-03
影响因子：
3.6
通讯作者：
Hadd, MJ
中科院分区：
文献类型：
--
作者：
Gervay, J;Hadd, MJ
经典的，糖基卤化物被激活作为糖基供体通过金属螯合在柯尼希-克诺尔或Helferich条件下。这些反应通常通过氧鎓形成进行，而立体化学的结果是由C2羟基上的端粒效应和/或保护基团的性质决定的。或者，糖基卤化物可以通过S(N)2机制被进入的亲核试剂直接取代。后一种反应远不常见，在本研究之前，它主要是用糖基溴进行的。在最近证明了碘化糖基和碘化糖基都可以有效地生成后，我们开始了对碘化糖基的亲核添加的研究。本文报道的研究表明，即使在没有C2参与基团的情况下，向α -糖基碘化物添加稳定阴离子也会通过立体化学反转得到β -糖苷。对葡萄糖基、半乳糖基和甘露糖基碘化物进行了研究，综合结果表明，2,3,4,6-四- o -苄基- α - d -半乳糖基碘化物> 2,3,4,6-四- o -苄基- α - d -甘露糖基碘化物> 2,3,4,6-四- o -苄基- α - d -甘露糖基碘化物的反应活性。当用高碱性阴离子处理时，葡萄糖基和半乳糖基碘化物都容易被E-2消除。相反，甘露糖基碘化物经过取代得到1,2顺式构型。整个序列包括一个头型醋酸酯与三甲基硅基碘化物的反应，并在真空中除去所得的三甲基硅基醋酸酯。然后用亲核试剂处理碘化物，而不作进一步的表征。各种亲核试剂被立体选择性地添加到糖基卤化物上，形成-、C-、N-和o -糖苷。
Classically, glycosyl halides are activated as glycosyl donors by metal chelation under Koenigs-Knorr or Helferich conditions. These reactions often proceed through oxonium formation, and the stereochemical outcome is dictated by the anomeric effect and/or the nature of the protecting group on the C2 hydroxyl. Alternatively, glycosyl halides may undergo direct displacement of the halide by an incoming nucleophile in an S(N)2 mechanism. The latter reaction is far less common, and before this study it was primarily performed with glycosyl bromides. Having recently shown that both alpha and beta glycosyl iodides could be efficiently generated, we embarked upon an investigation of nucleophilic additions to glycosyl iodides. The studies reported herein show that additions of stabilized anions to alpha-glycosyl iodides proceed with inversion of stereochemistry to give beta-glycosides, even in the absence of a C2 participatory group. Glucosyl, galactosyl, and mannosyl iodides were studied, and the combined results indicate that the reactivity of 2,3,4,6-tetra-O-benzyl-alpha-D-galactosyl iodide > 2,3,4,6-tetra-O-benzyl-alpha-D-glucosyl iodide > 2,3,4,6-tetra-O-benzyl-alpha-D-mannosyl iodide. Both the glucosyl and galactosyl iodides are susceptible to E-2 elimination when treated with highly basic anions. In contrast, the mannosyl iodide undergoes substitution to give the 1,2 cis configuration. The overall sequence involves reaction of an anomeric acetate with trimethylsilyl iodide with in vacuo removal of the resulting trimethylsilyl acetate. The iodide is then treated with a nucleophile without further characterization. A variety of nucleophiles were stereoselectively added to the glycosyl halides providing beta-, C-, N-, and O-glycosides.