A Mechanistic Probe into 1,2-cis Glycoside Formation Catalyzed by Phenanthroline and Further Expansion of Scope.
A Mechanistic Probe into 1,2-cis Glycoside Formation Catalyzed by Phenanthroline and Further Expansion of Scope.
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DOI：
10.1002/adsc.202100639
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发表时间：
2021-08-13
影响因子：
5.4
通讯作者：
Nguyen, Hien M.
中科院分区：
文献类型：
--
作者：
Li, Jiayi;Nguyen, Hien M.
关键词：
菲罗啉是一种刚性的平面化合物，具有两个融合的吡啶环，已被用作金属的强配体和DNA/RNA的结合剂。我们发现，邻菲罗啉可以作为亲核催化剂，通过羟基受体与α-糖基溴供体的偶联，有效地获得高产、非对映选择性的α-1,2-顺式糖苷。我们对反应机理进行了广泛的研究，其中两个糖基苯咯啉离子中间体，一个4C1椅子状β-构象和一个B2,5船状α-构象，通过变温核磁共振实验以2:1的比例（β:α）检测到。此外，核磁共振研究表明，邻菲罗啉的第二个氮原子与糖部分的c1 -端粒氢之间形成氢键，以稳定邻菲罗啉离子中间体。为了获得高的α-1,2-顺式立体选择性，提出了一种Curtin-Hammett情景，其中4C1椅状β-构象与B2,5船状α-构象的相互转化比亲核加成更快。羟基攻击发生在反应性较强的4C1 β-邻菲罗啉中间体的α-面，生成α-端粒产物。邻菲罗啉的催化作用扩展到位阻羟基亲核试剂和烷基羟基在游离c1 -半缩醛存在下的化学选择性偶联。此外，基于邻菲罗啉的催化剂对三醇基序的选择性偶联有明显的影响，并在氟和硫化物的端粒上正交激活端粒溴的离去基。
Phenanthroline, a rigid and planar compound with two fused pyridine rings, has been used as a powerful ligand for metals and a binding agent for DNA/RNA. We discovered that phenanthroline could be used as a nucleophilic catalyst to efficiently access high yielding and diastereoselective α-1,2-cis glycosides through the coupling of hydroxyl acceptors with α-glycosyl bromide donors. We have conducted an extensive investigation into the reaction mechanism, wherein the two glycosyl phenanthrolinium ion intermediates, a 4C1 chair-liked β-conformer and a B2,5 boat-like α-conformer, have been detected in a ratio of 2:1 (β:α) using variable temperature NMR experiments. Furthermore, NMR studies illustrate that a hydrogen bonding is formed between the second nitrogen atom of phenanthroline and the C1-anomeric hydrogen of sugar moiety to stabilize the phenanthrolinium ion intermediates. To obtain high α-1,2-cis stereoselectivity, a Curtin-Hammett scenario was proposed wherein interconversion of the 4C1 chair-like β-conformer and B2,5 boat-like α-conformer is more rapid than nucleophilic addition. Hydroxyl attack takes place from the α-face of the more reactive 4C1 β-phenanthrolinium intermediate to give an α-anomeric product. The utility of the phenanthroline catalysis is expanded to sterically hindered hydroxyl nucleophiles and chemoselective coupling of an alkyl hydroxyl group in the presence of a free C1-hemiacetal. In addition, the phenanthroline-based catalyst has a pronounced effect on site-selective couplings of triol motifs and orthogonally activates the anomeric bromide leaving group over the anomeric fluoride and sulfide counterparts.
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影响因子：
15
作者：
Garcia, BA;Gin, DY
通讯作者：
Gin, DY
影响因子：
4.4
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BECKE, AD
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作者：
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通讯作者：
POPLE, JA
影响因子：
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DITCHFIELD, R;HEHRE, WJ;POPLE, JA
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