We report the development and optimization of a scalable flow process for metallaphotoredox (Ir/Ni) C–O coupling, a mild and efficient approach for forming alkyl-aryl ethers, a common motif in medicinal and process chemistry settings. Time-resolved infrared spectroscopy (TRIR) highlighted the amine as the major quencher of the photocatalyst triplet excited state, along with the formation of an Ir(II) species that, in the presence of the Ni cocatalyst, has its lifetime shortened, suggesting reductive quenching of Ir(III)*, followed by reoxidation facilitated by the Ni cocatalyst. TRIR and batch reaction screening was used to develop conditions transferrable to flow, and many processing benefits of performing the reaction in flow were then demonstrated using a simple to construct/operate, small-footprint FEP coil flow reactor, including short (<10 min) space times and reduced catalyst loadings (down to 0.1 mol % Ir, 1 mol % Ni) while retaining good yield/conversion. Scalability was demonstrated by increasing the length or diameter of the FEP coil flow reactor tubing, however, due to suspected mass transfer/mixing limitations, the yield decreased upon scale-up in some cases. Therefore, we applied a modified version of our previously reported photochemical Taylor Vortex Flow Reactor (PhotoVortex), where Taylor vortices and a short-irradiated path length allow photochemical reactions to be performed efficiently via excellent mixing. In a small PhotoVortex (8 mL irradiated volume), we have demonstrated projected productivities around 1 kg day^–1 and >10 kg day^–1 in a large PhotoVortex (185 mL irradiated volume) with good product yields (>90%) and low catalyst loadings (0.1 to 0.5 mol % of [Ir{dF(CF₃)ppy}₂dtbbpy]PF₆), enabled by excellent mixing ensuring sufficient mass transfer between short-lived photoexcited and other transient species.

中文翻译：

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使用小占地面积光化学泰勒涡流反应器将连续金属光氧化还原催化的 C-O 偶联放大至 10 kg 规模


我们报道了用于金属光氧化还原 （Ir/Ni） C-O 偶联的可扩展流动工艺的开发和优化，这是一种形成烷基芳基醚的温和而有效的方法，烷基芳基醚是药物和工艺化学环境中的常见基序。时间分辨红外光谱 （TRIR） 强调胺是光催化剂三重态激发态的主要淬灭剂，同时形成 Ir（II） 物质，在 Ni 助催化剂存在下，其寿命缩短，表明 Ir（III）* 的还原猝灭，然后是 Ni 助催化剂促进的再氧化。使用 TRIR 和间歇反应筛选来开发可转移到流动的条件，然后使用易于构建/操作、占地面积小的 FEP 盘流反应器展示了在流动中进行反应的许多加工优势，包括短 （<10 min） 空间时间和减少催化剂负载（低至 0.1 mol % Ir，1 mol % Ni），同时保持良好的产率/转化率。通过增加 FEP 盘流反应器管的长度或直径证明了可扩展性，但是，由于可能的传质/混合限制，在某些情况下，产量在放大后会降低。因此，我们应用了之前报道的光化学泰勒涡流反应器 （PhotoVortex） 的改进版本，其中泰勒涡流和短辐照光程允许通过出色的混合有效地进行光化学反应。在小的 PhotoVortex（8 mL 辐照体积）中，我们已经证明，在大的 PhotoVortex（185 mL 辐照体积）中，预计产量约为 1 kg day^–1 和 >10 kg day^–1，具有良好的产品产率 （>90%） 和低催化剂负载量 （0.1 至 0.5 mol % 的 [Ir{dF（CF₃）ppy}₂dtbbpy]PF₆），通过出色的混合实现，确保在短寿命光激发物质和其他瞬态物质之间实现足够的质量传递。