Division of Chemistry &Biological Chemistry, School of Physical &Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
1] Division of Chemistry &Biological Chemistry, School of Physical &Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore [2] Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China.
Nat Commun. 2014 Sep 25;5:5027. doi: 10.1038/ncomms6027.
The benzene unit, in its substituted forms, is a most common scaffold in natural products, bioactive molecules and polymer materials. Nearly 80% of the 200 best selling small molecule drugs contain at least one benzene moiety. Not surprisingly, the synthesis of substituted benzenes receives constant attentions. At present, the dominant methods use pre-existing benzene framework to install substituents by using conventional functional group manipulations or transition metal-catalyzed carbon-hydrogen bond activations. These otherwise impressive approaches require multiple synthetic steps and are ineffective from both economic and environmental perspectives. Here we report an efficient method for the synthesis of substituted benzene molecules. Instead of relying on pre-existing aromatic rings, here we construct the benzene core through a carbene-catalyzed formal [3+3] reaction. Given the simplicity and high efficiency, we expect this strategy to be of wide use especially for large scale preparation of biomedicals and functional materials.
苯环及其取代形式是天然产物、生物活性分子和聚合物材料中最常见的支架。近 80%的 200 种畅销小分子药物至少含有一个苯环。毫不奇怪，取代苯的合成一直受到关注。目前，主要方法是使用预先存在的苯框架，通过常规的官能团操作或过渡金属催化的碳-氢键活化来安装取代基。这些令人印象深刻的方法需要多个合成步骤，从经济和环境的角度来看都是无效的。在这里，我们报告了一种合成取代苯分子的有效方法。我们不是依赖于预先存在的芳香环，而是通过卡宾催化的正规[3+3]反应构建苯核。由于方法简单高效，我们预计这种策略将得到广泛应用，特别是在生物医学和功能材料的大规模制备方面。
