Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia.
Molecules. 2022 Oct 14;27(20):6889. doi: 10.3390/molecules27206889.
Reactions of oxirane ring opening provide a powerful tool for regio- and stereoselective synthesis of polyfunctional and heterocyclic compounds, widely used in organic chemistry and drug design. Cyclooctane, alongside other medium-sized rings, is of interest as a novel molecular platform for the construction of target-oriented leads. Additionally, cyclooctane derivatives are well known to be prone to transannular reactions, which makes them a promising object in the search for novel approaches to polycyclic structures. In the present work, a series of cyclooctanediones was studied in Corey-Chaykovsky reactions, and novel spirocyclic bis(oxiranes) containing cyclooctane core, namely, 1,5-dioxadispiro[2.0.2.6]dodecane and 1,8-dioxadispiro[2.3.2.3]dodecane, were synthesized. Ring opening of the obtained bis(oxiranes) upon treatment with sodium azide was investigated, and it was found that the reaction path is determined by the reciprocal orientation of oxygen atoms in the oxirane moieties. Diastereomers of the bis(oxiranes) with -orientation underwent independent ring opening, supplying corresponding diazidodiols, while in the case of stereoisomers with -orientation, domino-like reactions occurred, including intramolecular nucleophilic attack and the formation of a novel three- or six-membered O-containing ring. Summarily, a straightforward approach to polyfunctional compounds containing cyclooctane or oxabicyclo[3.3.1]nonane cores, employing bis(oxiranes), was elaborated.
环氧化合物的开环反应为区域和立体选择性合成多功能和杂环化合物提供了有力工具，广泛应用于有机化学和药物设计中。环辛烷与其他中等大小的环一样，作为构建靶向先导化合物的新型分子平台具有重要意义。此外，环辛烷衍生物易于发生环烷反应，这使得它们成为寻找新型多环结构方法的有前途的目标。在本工作中，对一系列环辛二酮进行了 Corey-Chaykovsky 反应研究，并合成了含有环辛烷核的新型螺环双（环氧乙烷），即 1,5-二氧代双螺[2.0.2.6]十二烷和 1,8-二氧代双螺[2.3.2.3]十二烷。研究了所得双（环氧乙烷）在叠氮化钠作用下的开环反应，发现反应路径由环氧乙烷部分中氧原子的相互取向决定。具有 -取向的双（环氧乙烷）的非对映异构体发生独立开环，提供相应的叠氮二醇，而具有 -取向的立体异构体则发生类似多米诺的反应，包括分子内亲核攻击和形成新的三或六元含 O 环。总之，提出了一种利用双（环氧乙烷）制备含有环辛烷或氧杂双环[3.3.1]壬烷核的多功能化合物的简便方法。
