An Intramolecular Diels‐Alder cycloaddition reaction between a furan diene and an alkynic dienophile was performed within a flow hydrogenator fitted with an inert titanium column at 150 °C, no H₂, under 100 bar pressure. A single column pass (t_R=1.6 min) afforded ≈55% conversion to the tetrahydroepoxyisoindole carboxamide scaffold with a product turnover of ≈0.035 g/h, a 95% improvement over batch procedures. The cycloaddition protocol is performed in water and ethanol, and does not require catalysts or other additives. Quantitative hydrogenation of the resulting dual π‐bonds within the oxabicyclo system was effected with either a 10% Pd/Al₂O₃ or 10% Pd/CaCO₃ catalyst at 20 °C, 20 bar, with full H₂ whereas utilisation of a Raney Ni catalyst under these conditions resulted in a quantitative mono‐olefin reduction of the C4‐C5 double‐bond. With regard to di‐olefin reduction, a degree of stereoselectivity was observed with the aforementioned palladium‐based catalysts yielding exclusive formation of (R) configuration at C7 while utilisation of a 5% Pt/C (sulfided) catalyst at temperatures below 60 °C promoted the formation of the (S)‐isomer at C7. Hence this work further highlights that flow‐hydrogenation provides unprecedented convenience for establishing robust protocols to effect chemoselective transformations.

中文翻译：

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化学选择性流加氢方法多样化的细胞毒性四氢环氧异吲哚羧酰胺支架。

在装有惰性钛柱的流动氢化器中，于150°C，无H ₂的流动氢化器中，于100 bar压力下，进行呋喃二烯与炔烃二烯之间的分子内Diels-Alder环加成反应。单次通过色谱柱（t _R = 1.6分钟）可提供约55％的四氢环氧异吲哚羧酰胺支架转化率，产品周转率约为0.035 g / h，比批处理过程提高了95％。环加成方案在水和乙醇中进行，不需要催化剂或其他添加剂。在氧双环体系中生成的双π键的定量加氢是通过10％Pd / Al ₂ O ₃或10％Pd / CaCO _3进行的催化剂在20°C，20巴，全H _2的条件下使用，而在这些条件下使用阮内镍催化剂会使C4-C5双键的单烯烃定量降低。关于二烯烃的还原，上述钯基催化剂在C7产生独家形成（R）构型，同时在60°C以下的温度下使用5％Pt / C（硫化）催化剂时观察到一定程度的立体选择性促进了C7上（S）异构体的形成。因此，这项工作进一步强调了流加氢为建立有效的化学选择转化方案提供了前所未有的便利。