Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor

Abstract

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.

Coordination assembly enables highly selective catalytic hydroaminomethylation of olefins

“…8,11,12 Therefore, various efforts have thus been devoted to the design of bi-functional catalytic systems. [20][21][22][23][24][25][26][27] By using 2-fluoro-4-methylbenzoic acid as a co-catalyst, Abolhasani and co-workers increased the reactivity of Rh/4,5-bis(diphenylphosphino)-9,9-dimethyl-xanthene by 70-fold in HAM. 20 Chen's group synthesized water-soluble diphosphine ligands and applied them in Rh-catalyzed HAM of vinylarenes using anilines in water with good branch selectivity.…”

A versatile non-fouling multi-step flow reactor platform: demonstration for partial oxidation synthesis of iron oxide nanoparticles

“…[8][9][10][11][12][13] Not only for fine chemical, but also polymer as well as micro and nanoparticle synthesis, such platforms combining flow reactors, intelligent algorithms and real-time material characterisation can pave the way to fully computer aided chemical science tuning molecular or particle properties. [14][15][16][17][18][19] The commonly used flow reactors which were developed for wet-chemical syntheses of small and large molecules, however, are often unsuitable for fouling prone syntheses, and nano or micro particle syntheses in particular. This is because (nano) particle formation, and any formation of solid matter from solution, is likely to foul the reactor walls.…”

“…8–13 Not only for fine chemical, but also polymer as well as micro and nanoparticle synthesis, such platforms combining flow reactors, intelligent algorithms and real-time material characterisation can pave the way to fully computer aided chemical science tuning molecular or particle properties. 14–19…”

2‐Arylpropylamines from 1‐Propenylbenzenes in a New One‐Pot Metathesis–Hydroaminomethylation Protocol

“…Rh-catalyzed HAM has been recently used for the synthesis of indoles or indoline-2-ols, [13] gamma-aminobutyric esters, [14] beta-aminoesters [15] in homogeneous catalysis. Also, in several recent studies the catalyst was supported on an immiscible liquid phase [16][17][18][19] or on polymers [20,21] to facilitate the recycling. The use of an additional catalyst for the reductive amination step allowed for a drastic reduction on the temperature and syngas pressure.…”