Fast and Enantioselective Production of 1‐Aryl‐1‐propanols through a Single Pass, Continuous Flow Process

Abstract

A functional polymer 4, obtained by reaction of (R)-2-(1-piperazinyl)-1,1,2-triphenylethanol with a Merrifield resin, has been loaded in a packed bed reactor and used as catalyst for the continuous enantioselective production of 1-arylpropanols by ethylation of aromatic aldehydes. The high catalytic activity depicted by 4 allows the complete conversion of the substrates with the use of stoichiometric reagent ratios and unprecedently short residence times (down to 2.8 min). In practice, a single-pass operation can be used for all the studied aldehydes, and productions of up to 13.0 mol/g h are recorded. The sequential operation of the flow system for the uninterrupted synthesis of a small library of enantiopure 1-arylpropanols is also reported.

Asymmetric reactions in continuous flow

“…A fast, single pass continuous flow process for the addition of diethylzinc to various aldehydes was described recently (Scheme 4) [27]. Reagent solutions were fed by piston-pump driven flow through a fritted column packed with chiral amino-alcohol functionalized Merrifield resin 9 .…”

Recyclable Stereoselective Catalysts

“…Recently, such polymeric ligand was effi ciently applied under a continuous -fl ow process. The high catalytic activity of this system allowed complete conversion of substrates with the use of stoichiometric reagent ratios and unprecedented short residence times (less than 3 minutes) [204] . Fig.…”

An Overview of Polymer‐Immobilized Chiral Catalysts and Synthetic Chiral Polymers

“…Once the reaction is complete, the species supported on the polymer will be easily separated from the others by simple filtration [57]. The continuous flow system has been applied to various asymmetric reactions, including asymmetric Michael reacions [59] and alkylation [60,61]. The advantage of the continuous system in organic synthesis is that it allows the products of the reaction to be isolated more quickly and easily than traditional methods.…”