Formic Acid as Carbon Monoxide Source in the Palladium-Catalyzed N‑Heterocyclization of <i>o</i>‑Nitrostyrenes to Indoles

The reductive cyclization reaction of o-nitrostyrenes to generate indoles has been investigated for three decades using CO as a cheap reducing agent, but it remains an interesting area of research and improvements. However, using toxic CO gas has several drawbacks. As a result, it is highly preferable to use safe and efficient surrogates for in situ generation of CO from nontoxic and affordable sources. Among several CO sources that have been previously explored for the generation of gaseous CO, here we report the use of cheap and readily available formic acid as an effective reductant for the reductive cyclization of o-nitrostyrenes. The reaction is air and water tolerant and provides the desired indoles in yields up to 99%, at a low catalyst loading (0.5 mol %) and without generating toxic or difficult to separate byproducts. A cheap glass thick-walled “pressure tube” can be used instead of less available autoclaves, even on a 2 g scale, thus widening the applicability of our protocol.邻硝基苯乙烯（o-nitrostyrenes）还原环化生成吲哚（indoles）的反应，以一氧化碳（CO）作为廉价还原剂的研究已开展三十年，但该领域仍是值得持续探索与优化的研究方向。然而，使用有毒的一氧化碳气体存在诸多弊端。因此，从无毒且易得的原料中原位生成一氧化碳的安全高效替代方案，成为极具吸引力的选择。在以往报道的多种气态一氧化碳生成源中，本文采用廉价易得的甲酸（formic acid）作为邻硝基苯乙烯还原环化反应的高效还原剂。 该反应具有良好的空气与水耐受性，在催化剂负载量仅为0.5 mol%的条件下，目标吲哚产物的收率最高可达99%，且不会产生有毒或难以分离的副产物。无需使用难以获取的高压釜（autoclaves），仅需廉价的厚壁玻璃“耐压管”即可完成反应，反应规模甚至可达2克级，进一步拓展了该方案的适用范围。