Chelate-Assisted Ring-Closing Metathesis: A Strategy for Accelerating Macrocyclization at Ambient Temperatures
Chelate-Assisted Ring-Closing Metathesis: A Strategy for Accelerating Macrocyclization at Ambient Temperatures
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DOI：
10.1021/jacs.7b13257
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发表时间：
2018-02-07
影响因子：
15
通讯作者：
Fogg, Deryn E.
中科院分区：
文献类型：
--
作者：
Higman, Carolyn S.;Nascirnento, Daniel L.;Fogg, Deryn E.
闭合环复合（RCM）为大环提供了多种催化途径，其应用范围从香水到抗病毒药物的生产。然而，不需要的寡聚化是一个长期存在的挑战。低聚物可以通过反应性强的催化剂（如n -杂环碳化合物的Ru配合物；NHCs）转化为循环目标，但催化剂分解限制了产率和选择性。在RuCl2(NHC)(ODA)（=CHPh）形式的新催化剂中掺入半可溶的邻二苯胺（ODA）螯合物可加速大环化，特别是对于具有h键能力的极性位置的二烯；它还可能抑制催化剂在复分解过程中的分解。结果表明，相对于先前的Ru-NHC催化剂，室温下构象柔性二烯的大环化速度更快。
Ring-closing metathesis (RCM) offers versatile catalytic routes to macrocycles, with applications ranging from perfumery to production of antiviral drugs. Unwanted oligomerization, however, is a long-standing challenge. Oligomers can be converted into the cyclic targets by catalysts that are sufficiently reactive to promote backbiting (e.g., Ru complexes of N-heterocyclic carbenes; NHCs), but catalyst decomposition limits yields and selectivity. Incorporation of a hemilabile o-dianiline (ODA) chelate into new catalysts of the form RuCl2(NHC)(ODA)(=CHPh) accelerates macrocyclizalion, particularly for dienes bearing polar sites capable of H-bonding: it may also inhibit catalyst decomposition during metathesis. Significant improvements relative to prior Ru-NHC catalysts result, with fast macrocyclization of conformationally flexible dienes at room temperature.