Photoredox Iridium-Nickel Dual Catalyzed Cross-Electrophile Coupling: From a Batch to a Continuous Stirred-Tank Reactor via an Automated Segmented Flow Reactor
Photoredox Iridium-Nickel Dual Catalyzed Cross-Electrophile Coupling: From a Batch to a Continuous Stirred-Tank Reactor via an Automated Segmented Flow Reactor
复制标题
DOI：
10.1021/acs.oprd.1c00251
复制
发表时间：
2021-10-06
影响因子：
3.4
通讯作者：
Robinson, Richard, I
中科院分区：
文献类型：
--
作者：
Duvadie, Rohit;Pomberger, Alexander;Robinson, Richard, I
在药物合成过程中，有机反应的优化是一个主要的挑战。几个因素，如反应物浓度，停留/反应时间，或同质/异质性需要考虑在微调反应条件向典型的规模扩大的目标，如高时空产率。在此，我们提出了光氧化还原铱-镍双催化交叉亲电偶联的反应优化，重点是开发均匀的起始条件。在筛选过程中，特别注意用均相有机碱代替无机碱，并研究了pK（a）对反应产率的影响。通过15 μ L规模的自动化分段流动反应器进行筛选，并随后将条件转移到5 mL光连续搅拌釜反应器（CSTR）级联中，以证明在24小时稳定操作期间的多克连续流动合成。
Organic reaction optimization for batch to flow transfer represents a main challenge for process chemists in drug synthesis. Several factors such as reactant concentration, residence/reaction time, or homo-/heterogeneity need to be taken into consideration during the fine-tuning of reaction conditions toward typical scale-up goals, such as high space-time yield. Herein, we present reaction optimization for photoredox iridium-nickel dual catalyzed cross-electrophile coupling with a focus on developing homogeneous starting conditions. During the screening, special attention was put on the replacement of inorganic bases with homogeneous organic bases, and the effect of pK(a) on the reaction yield was investigated. Screening was conducted via an automated segmented flow reactor at 15 mu L scale, and subsequentially, the conditions were transferred to a 5 mL photo-continuous stirred-tank reactor (CSTR) cascade to demonstrate multigram continuous flow synthesis during a 24 h steady operation.