Radical Cyclization onto Polar Unsaturated Bonds. A New Method for the Synthesis of Nitrogen-Heterocycles

极性不饱和键上的自由基环化。

基本信息

批准号：
12440177
负责人：
RYU Ilhyong
金额：
$ 7.3万
依托单位：
Osaka Prefecture University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

The aim of this work is to develop a new class of radical cyclization reactions available for the synthesis of nitrogen-heterocycles. We investigated radical cyclization which employs a system that both attacking radical and accepting unsaturation have a polarity, under the hypothesis that the polarity-matching would boost the desired cyclization mode. Acyl radicals generally behave as nucleophilic radical, however the carbonyl carbon should have an electrophilic nature. Thus, we examined the reaction of ω-imino alkyl radicals with CO in detail and observed that the complete exo-mode cyclization leading to lactam rings. Ab initio and DFT MO calculations revealed the transition state of the cyclization is akin to that of nucleophilic attack of imine-nitrogen to aldehyde, supporting that polar interaction between attacking radical site and accepting N-C double bond is crucial. Having a strong support from the calculation, we then embarked on the work to find powerful radical cyclization systems boosted by polarity-matching, and found that stannylcarbonylation reaction of azaenynes is particularly useful reaction in its unusual breath in the cyclization modes covering 4-exo, 5-exo, 6-exo, 7-exo, and even 8-exo. With this novel cyclization method in hand, four to eight membered ring lactarns having an α-stannylmethylene group can be prepared conveniently. The resulting Sn-C bond was successfully converted to the corresponding H-C, I-C, and C-C bonds by the subsequent protonation, iodination, and Stille coupling reaction. The carbonylative cyclization of enynes was further extended to include those with (TMS)_3SiH and alkane thiols as radical mediators. Thus, we have established a new concept of polarity-governed radical cyclization with convincing results available for α-methylene lactam synthesis, whose basic principle would have a general applications in radical reactions.

这项工作的目的是开发一类可用于合成氮杂环的新型自由基环化反应，我们研究了自由基环化反应，该反应采用了攻击自由基和接受不饱和度都具有极性的系统，假设极性-匹配将增强所需的环化模式。酰基通常表现为亲核自由基，但羰基碳应具有亲电子性质，因此，我们研究了 ω-亚氨基的反应。详细观察了烷基自由基与CO的相互作用，并观察到从头开始形成内酰胺环的完整外模式环化和DFT MO计算表明环化的过渡态类似于亚胺氮对醛的亲核攻击，支持了极性。攻击自由基位点和接受N-C双键之间的相互作用至关重要，得到了计算的有力支持，我们开始寻找由其推动的强大的自由基环化系统。极性匹配，发现氮杂烯炔的甲锡烷基羰基化反应在其不寻常的呼吸中在涵盖4-exo、5-exo、6-exo、7-exo甚至8-exo的环化模式中是特别有用的反应。通过现有的方法，可以方便地制备具有α-甲锡烷基亚甲基的四至八元环内酰胺，并将所得的Sn-C键成功地转化为Sn-C键。通过随后的质子化、碘化和 Stille 偶联反应，生成相应的 H-C、I-C 和 C-C 键。烯炔的羰基环化进一步扩展到以 (TMS)_3SiH 和烷硫醇作为自由基介体。极性控制的自由基环化的新概念，为α-亚甲基内酰胺的合成提供了令人信服的结果，其基本原理将在自由基反应中具有普遍的应用。