Department of Chemistry, University of Oxford, Oxford, OX1 3TA UK.
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3373-6. doi: 10.1073/pnas.0913466107. Epub 2010 Feb 8.
The olefin cross-metathesis (CM) reaction is used extensively in organic chemistry and represents a powerful method for the selective synthesis of differentially substituted alkene products. Surprisingly, efforts to integrate this remarkable process into strategies for aromatic and heteroaromatic construction have not been reported. Such structures represent key elements of the majority of small molecule drug compounds; methods for the controlled preparation of highly substituted derivatives are essential to medicinal chemistry. Here we show that the olefin CM reaction, in combination with an acid cocatalyst or subsequent Heck arylation, provides a concise and flexible entry to 2,5-di- or 2,3,5-tri-substituted furans. These cascade processes portend further opportunities for the regiocontrolled preparation of other highly substituted aromatic and heteroaromatic classes.
烯烃交叉复分解（CM）反应在有机化学中得到广泛应用，是一种用于选择性合成不同取代烯烃产物的有力方法。令人惊讶的是，将这一显著过程整合到芳香族和杂芳香族构建策略中的努力尚未得到报道。这些结构是大多数小分子药物化合物的关键元素；对于控制高度取代衍生物的制备方法对药物化学至关重要。在这里，我们表明烯烃 CM 反应与酸助催化剂或随后的 Heck 芳基化反应相结合，为 2,5-二取代或 2,3,5-三取代呋喃的制备提供了一种简洁灵活的方法。这些级联过程预示着进一步实现其他高度取代的芳香族和杂芳香族类别的区域控制制备的机会。
