Leiden Institute of Chemistry, Leiden University , Einsteinweg 55, 2333 CC Leiden, The Netherlands.
J Org Chem. 2017 May 5;82(9):4793-4811. doi: 10.1021/acs.joc.7b00470. Epub 2017 Apr 25.
Glycosylations of 4,6-tethered glucosazide donors with a panel of model acceptors revealed the effect of acceptor nucleophilicity on the stereoselectivity of these donors. The differences in reactivity among the donors were evaluated in competitive glycosylation reactions, and their relative reactivities were found to be reflected in the stereoselectivity in glycosylations with a set of fluorinated alcohols as well as carbohydrate acceptors. We found that the 2-azido-2-deoxy moiety is more β-directing than its C-2-O-benzyl counterpart, as a consequence of increased destabilization of anomeric charge development by the electron-withdrawing azide. Additional disarming groups further decreased the α-selectivity of the studied donors, whereas substitution of the 4,6-benzylidene acetal with a 4,6-di-tert-butyl silylidene led to a slight increase in α-selectivity. The C-2-dinitropyridone group was also explored as an alternative for the nonparticipating azide group, but this protecting group significantly increased β-selectivity. All studied donors exhibited the same acceptor-dependent selectivity trend, and good α-selectivity could be obtained with the weakest acceptors and most reactive donors.
用一系列模型受体对 4,6-键合的葡萄糖氮苷供体进行糖基化反应，揭示了受体亲核性对这些供体立体选择性的影响。在竞争性糖基化反应中评估了供体之间的反应性差异，并发现它们的相对反应性反映在与一组氟化醇和糖受体的糖基化中的立体选择性中。我们发现，2-叠氮基-2-脱氧部分比其 C-2-O-苄基对应物更具β-导向性，这是由于吸电子叠氮化物增加了对端基电荷发展的不稳定性。额外的去稳定基团进一步降低了研究供体的α选择性，而用 4,6-二叔丁基硅基取代 4,6-亚苄基缩醛则导致α选择性略有增加。还探索了 C-2-二硝基吡啶酮基团作为非参与性叠氮基团的替代物，但该保护基团显著增加了β选择性。所有研究的供体都表现出相同的受体质子化依赖选择性趋势，并且可以用最弱的受体和最具反应性的供体获得良好的α选择性。
