Department of Chemistry, University of California, Irvine, California 92697-2025, USA.
J Org Chem. 2010 Feb 19;75(4):1107-18. doi: 10.1021/jo902222a.
Nucleophilic substitution reactions of 2-deoxyglycosyl donors indicated that the reactivity of the oxygen nucleophile has a significant impact on stereoselectivity. Employing ethanol as the nucleophile resulted in a 1:1 (alpha:beta) ratio of diastereomers under S(N)1-like reaction conditions. Stereoselective formation of the 2-deoxy-alpha-O-glycoside was only observed when weaker nucleophiles, such as trifluoroethanol, were employed. The lack of stereoselectivity observed in reactions of common oxygen nucleophiles can be attributed to reaction rates of the stereochemistry-determining step that approach the diffusion limit. In this scenario, both faces of the prochiral oxocarbenium ion are subject to nucleophilic addition to afford a statistical mixture of diastereomeric products. Control experiments confirmed that all nucleophilic substitution reactions were performed under kinetic control.
2-脱氧糖基给体的亲核取代反应表明，氧亲核试剂的反应性对立体选择性有重大影响。在 S(N)1 类似反应条件下，使用乙醇作为亲核试剂得到 1:1(α:β)的非对映异构体比率。只有当使用较弱的亲核试剂，如三氟乙醇时，才观察到 2-脱氧-α-O-糖苷的立体选择性形成。在常见的氧亲核试剂反应中观察到的立体选择性缺失可以归因于决定立体化学的步骤的反应速率接近扩散极限。在这种情况下，手性 oxocarbenium 离子的两个面都受到亲核加成的影响，得到非对映异构体产物的统计混合物。对照实验证实，所有亲核取代反应都是在动力学控制下进行的。
