Mechanistic Studies of Bismuth(V)-Mediated Thioglycoside Activation Reveal Differential Reactivity of Anomers
Mechanistic Studies of Bismuth(V)-Mediated Thioglycoside Activation Reveal Differential Reactivity of Anomers
复制标题
DOI：
10.1021/acs.joc.6b00860
复制
发表时间：
2016-07-15
影响因子：
3.6
通讯作者：
Pohl, Nicola L. B.
中科院分区：
文献类型：
--
作者：
Goswami, Manibarsha;Ashley, Daniel C.;Pohl, Nicola L. B.
采用反应动力学和量子化学反应模型研究了铋（V）介导的硫代糖苷活化机制。NMR实验显示糖基化反应的不寻常的非线性增长/衰减曲线。进一步的研究表明，在其活化过程中，即使在相邻的2-位乙酸酯的存在下，β-糖苷供体也会异头转化为α-供体。有趣的是，在α-糖苷供体的活化中没有观察到原位端基异构化，并且该端基异构体还显示出更快的反应时间和更高的产物非对映选择性。密度泛函理论计算确定了促进剂三苯基铋二三氟甲磺酸盐[Ph 3Bi（OTf）（2），1]在溶液中的结构，并绘制出其与两种硫代糖苷端基异构体相互作用的能量学。这些计算表明，1必须结合硫代丙基臂，以诱导三氟甲磺酸酯损失。计算分析还表明，与大多数O-糖苷不同，β-和α-供体S-糖苷的能量相似。一种能量上合理的供体的端基异构化途径是通过与刘易斯酸性Bi（V）形成铋-锍加合物以形成氧杂卡宾中间体而促进的S（N）1-样机理。最后，计算的能量补偿需要形成这些α与β Bi加合物是这些捐助者的差分反应性的一个可能的解释。
The mechanism of bismuth(V)-mediated thioglycoside activation was examined using reaction kinetics and quantum chemical reaction models. NMR experiments show an unusual nonlinear growth/decay curve for the glycosylation reaction. Further studies suggest an anomeric inversion of the beta-glycoside donor to the alpha-donor during its activation, even in the presence of a neighboring 2-position acetate. Interestingly, in situ anomerization was not observed in the activation of an alpha-glycoside donor, and this anomer also showed faster reaction times and higher product diastereoselectivites. Density functional theory calculations identify the structure of the promoter triphenyl bismuth ditriflate, [Ph3Bi(OTf)(2), 1], in solution and map out the energetics of its interactions with the two thioglycoside anomers. These calculations suggest that 1 must bind the thiopropyl arm to induce triflate loss. The computational analyses also show that, unlike most O-glycosides, the beta- and alpha-donor S-glycosides are similar in energy. One energetically reasonable anomerization pathway of the donors is an S(N)1-like mechanism promoted by forming a bismuth-sulfonium adduct with the Lewis acidic Bi(V) for the formation of an oxacarbenium intermediate. Finally, the computed energy compensations needed to form these alpha vs beta Bi adducts is a possible explanation for the differential reactivity of these donors.