Stereoselective Synthesis of Ribofuranoid <i>exo</i>-Glycals by One-Pot Julia Olefination Using Ribofuranosyl Sulfones

One-pot Julia olefination using ribofuranosyl sulfones is described. The α-anomers of the ribofuranosyl sulfones were synthesized with complete α-selectivity via the glycosylation of heteroarylthiols using ribofuranosyl iodides as glycosyl donors and the subsequent oxidation of the resulting heteroaryl 1-thioribofuranosides with magnesium monoperphthalate (MMPP). The Julia olefination of the α-ribofuranosyl sulfones with aldehydes proceeded smoothly in one pot to afford the thermodynamically less stable (E)-exo-glycals with modest-to-excellent stereoselectivity (up to E/Z = 94:6) under the optimized conditions. The E selectivity was especially high for aromatic aldehydes. In contrast, the (Z)-exo-glycal was obtained as the main product with low stereoselectivity when the corresponding β-ribofuranosyl sulfone was used (E/Z = 41:59). The remarkable impact of the anomeric configuration of the ribofuranosyl sulfones on the stereoselectivity of the Julia olefination has been rationalized using density functional theory (DFT) calculations. The protected ribose moiety of the resulting exo-glycals induced completely α-selective cyclopropanation on the exocyclic carbon–carbon double bond via the Simmons–Smith–Furukawa reaction. The 2-cyanoethyl group was found to be useful for the protection of the exo-glycals, as it could be removed without affecting the exocyclic CC bond.本研究报道了以呋喃核糖基砜（ribofuranosyl sulfones）为底物的一锅法Julia烯化反应（Julia olefination）。呋喃核糖基砜的α-端基异构体可通过以下步骤合成：以呋喃核糖基碘化物为糖基供体，与杂芳硫醇发生糖基化反应，再将生成的杂芳基1-硫代呋喃核糖苷经单过氧邻苯二甲酸镁（MMPP）氧化，最终以完全的α-选择性得到目标产物。在优化反应条件下，α-呋喃核糖基砜与醛类的一锅法Julia烯化反应可顺利进行，得到热力学稳定性更弱的(E)-外向型糖烯（exo-glycals），其立体选择性处于中等至优异水平，最高E/Z比可达94:6。对于芳香醛底物，该反应的E式立体选择性尤为突出。与之相对，当使用对应的β-呋喃核糖基砜作为底物时，主产物为(Z)-外向型糖烯，立体选择性较差，E/Z比仅为41:59。本研究通过密度泛函理论（DFT）计算，阐明了呋喃核糖基砜的端基构型对Julia烯化反应立体选择性的显著影响。所得外向型糖烯上的受保护核糖基团，可通过西蒙斯-史密斯-古川（Simmons–Smith–Furukawa）反应，在其环外碳碳双键上实现完全α-选择性的环丙烷化反应。研究发现2-氰乙基基团可用于外向型糖烯的保护，且该基团可在不破坏环外碳碳双键的前提下被脱除。