Ibrahim Malek Y S, Abolhasani Milad
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, 27695, USA.
Nat Commun. 2022 May 4;13(1):2441. doi: 10.1038/s41467-022-30175-0.
Synthesis of hindered amines using the atom-efficient hydroaminomethylation (HAM) route remains a challenge. Here, we report a general and accelerated HAM in segmented flow, achieved via a cooperative effect between rhodium (Rh)/N-Xantphos and a co-catalyst (2-Fluoro-4-methylbenzoic acid) to increase the reactivity by 70 fold when compared to Rh/Xantphos in batch reactors. The cooperation between Rh and the co-catalyst facilitates the cleavage of the H-H bond and drives the equilibrium-limited condensation step forward. Online reaction optimization expands the scope to include alkyl, aryl, and primary amines. In-flow solvent tuning enables selectivity switching from amine to enamine without the need for changing the ligand. Furthermore, leveraging the ionic nature of the catalyst, we present a robust Rh recovery strategy up to 4 recycles without loss of activity.
利用原子经济的氢氨甲基化（HAM）路线合成受阻胺仍然是一项挑战。在此，我们报道了一种在分段流中通用且加速的HAM方法，该方法通过铑（Rh）/N - Xantphos与助催化剂（2 - 氟 - 4 - 甲基苯甲酸）之间的协同作用实现，与间歇反应器中的Rh/Xantphos相比，反应活性提高了70倍。Rh与助催化剂之间的协同作用促进了H - H键的裂解，并推动了平衡受限的缩合步骤向前进行。在线反应优化扩大了适用范围，包括烷基、芳基和伯胺。流动相溶剂调节能够在不改变配体的情况下实现从胺到烯胺的选择性切换。此外，利用催化剂的离子性质，我们提出了一种稳健的Rh回收策略，可循环使用4次而不损失活性。
