Neighboring-Group Participation Involving the Oxygen Atom of the O,O- or O,N-Acetal Functional Groups
Neighboring-Group Participation Involving the Oxygen Atom of the O,O- or O,N-Acetal Functional Groups
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DOI：
10.2174/138527210791616777
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发表时间：
2010-08-01
影响因子：
2.6
通讯作者：
Campos, J. M.
中科院分区：
文献类型：
--
作者：
Kimatrai, M.;Cruz-Lopez, O.;Campos, J. M.
涉及O，O-或O，N-缩醛的氧原子的邻基参与的应用可以是非常富有成效的。例如，(Z)-己烷-3-烯-1，5-二炔的萘酸酯衍生物被用来通过伽马-氧代酮缩醛中间体生成双自由基，并通过1，3-二氧杂环戊环邻基参与的亲核置换合成了含手性氧硫环的三环9-冠-3醚。在不同的领域，研究了邻羟甲基苯氧乙醛二甲缩醛或(+/-)-3-methoxy-2，3-dihydro-5H-1，4-benzodioxepins与5-氟尿嘧啶的反应。分子内的环化反应可以通过邻基攻击得到2-(5-氟尿嘧啶-1-基)氧正离子，该离子可以被硅烷化的苄基羟基攻击而得到苯甲酰化的七元O，N-缩醛。在进行7-或9-取代(+/-)-2-methoxy-2，3-dihydro-5H-1，4-benzodioxepins的合成之前，需要对2-羟基苯甲醇的酚羟基进行保护。在其他功能中，2-甲氧基乙氧基甲基(MEM)被开发为醇和酚的保护基团。因此，决定使用MEM基团来制备7-或9-取代的(+/-)-2-methoxy-2，3-dihydro-5H-1，4-benzodioxepins及其十元苯并稠合类似物。十元O，O-缩醛的重要性揭示了邻基参与起关键作用的反应机理。该反应的跨环版本导致12元中间体向10元和7元苯稠合O，O-缩醛的简易环收缩。侧链含有多个氧原子的缩醛已被用于制备高氧环醚化合物。
The application of the neighboring-group participation involving the oxygen atom of O,O- or O,N-acetals can be very fruitful. For instance, the naphthoate ester derivatives of (Z)-hex-3-ene-1,5-diyne were used to generate biradicals via gamma-oxo ketene acetal intermediates, and a synthesis of tricyclic 9-crown-3 ethers bearing a chiral oxathiane ring was achieved by utilizing nucleophilic displacement of a triflic ester leaving-group assisted by neighbouring-group participation of a 1,3-dioxolane function. In a different field, the reaction between o-(hydroxymethyl)phenoxyacetaldehyde dimethyl acetals, or (+/-)-3-methoxy-2,3-dihydro-5H-1,4-benzodioxepins with 5-fluorouracil was studied. The intramolecular cyclization may be explained through a neighbouring-group attack to give a 2-(5-fluorouracil-1-yl)oxyranium ion that can be attacked by the silylated benzylic hydroxyl group to yield the benzannelated seven-membered O, N-acetals. Before carrying out the synthesis of 7- or 9-substituted (+/-)-2-methoxy-2,3-dihydro-5H-1,4-benzodioxepins it is necessary to protect the phenolic hydroxy group of the 2-hydroxybenzyl alcohol. Among other functionalities, the 2-methoxyethoxylmethyl (MEM) group was developed as a protective group of alcohols and phenols. Accordingly, it was decided to use the MEM group for the preparation of 7- or 9-substituted (+/-)-2-methoxy-2,3-dihydro-5H-1,4-benzodioxepins and their ten-membered benzo-fused analogs. The importance of the ten-membered O,O-acetals sheds light on the mechanism of reaction in which the neighbouring-group participation plays a pivotal role. Transannular versions of the reaction result in the facile ring contraction of 12-membered intermediates to the 10- and to 7-membered benzene-fused O,O-acetals. Acetals with several oxygen atoms in their side-chains have been used in the preparation of highly oxygenated cyclic ether compounds.