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新的自由基环化反应，可用于合成氮词汇。我们调查了激进的环化化，该系统在攻击自由基和接受不饱和的系统中具有极性，这是在极性匹配将增强所需环化模式的假设下。酰基自由基通常以核直线质自由基作用，但是羰基碳应具有亲电性质。这是我们详细研究了ω-imino烷基自由基与CO的反应，并观察到完整的Exo-Mode环化导致了Lactam环。从头开始和DFT MO计算表明，环化的过渡状态类似于亚胺氮对醛对醛的核热攻击，这支持了攻击自由基位点与接受N-C双键之间的极性相互作用至关重要。然后，我们在计算中得到了强有力的支持，然后开始了这项工作，以寻找通过极性匹配增强的强大的自由基环化系统，并发现Azaenynes的Stannylcarbonylation反应在涵盖4-EXO，5-EXO，6-EXO，6-EXO，7-EXO，7-EXO和8-- exo的环环中的异常呼吸中特别有用。借助这种新型的环化方法，可以方便地制备具有α-斯坦基甲基烯基的四到八个成员环乳糖。由此产生的SN-C键のですねのです。英语：通过随后的质子化，碘化和仍偶联的反应，它成功地转换为相应的H-C，I-C和C-C键。进一步扩展了Enynes的羰基环化，其中包括（TMS）_3SIH和Alkane硫醇作为激进介体。这是我们建立了一个新的极性支出自由基环化学的概念，可令人信服的结果可用于α-甲基乳酸合成，其基本原理将在自由基反应中具有一般应用。