Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science. 2018 Sep 21;361(6408):1220-1225. doi: 10.1126/science.aat0650.
Chemical synthesis generally requires labor-intensive, sometimes tedious trial-and-error optimization of reaction conditions. Here, we describe a plug-and-play, continuous-flow chemical synthesis system that mitigates this challenge with an integrated combination of hardware, software, and analytics. The system software controls the user-selected reagents and unit operations (reactors and separators), processes reaction analytics (high-performance liquid chromatography, mass spectrometry, vibrational spectroscopy), and conducts automated optimizations. The capabilities of this system are demonstrated in high-yielding implementations of C-C and C-N cross-coupling, olefination, reductive amination, nucleophilic aromatic substitution (SAr), photoredox catalysis, and a multistep sequence. The graphical user interface enables users to initiate optimizations, monitor progress remotely, and analyze results. Subsequent users of an optimized procedure need only download an electronic file, comparable to a smartphone application, to implement the protocol on their own apparatus.
化学合成通常需要劳动密集型、有时繁琐的反复试验来优化反应条件。在这里，我们描述了一种即插即用的连续流化学合成系统，通过硬件、软件和分析的集成组合来缓解这一挑战。系统软件控制用户选择的试剂和单元操作（反应器和分离器），处理反应分析（高效液相色谱、质谱、振动光谱），并进行自动化优化。该系统的功能在 C-C 和 C-N 交叉偶联、烯烃化、还原胺化、亲核芳香取代 (SAr)、光氧化还原催化和多步序列的高产实施中得到了证明。图形用户界面使用户能够启动优化、远程监控进度并分析结果。优化程序的后续用户只需下载电子文件，类似于智能手机应用程序，即可在自己的设备上实施该协议。
