Asymmetric α‐Amination of Aldehydes Catalyzed by PS‐Diphenylprolinol Silyl Ethers: Remediation of Catalyst Deactivation for Continuous Flow Operation

Abstract

Polystyrene (PS)-supported diphenylprolinol silyl ethers have been developed as highly active catalysts for the enantioselective a-amination of aldehydes. Understanding the mechanism of catalyst deactivation has led to the development of reaction conditions notably extending catalyst life in repeated recycling (10 cycles; accumulated TON of 480) and has allowed the implementation of a continuous flow a-amination process (6 min residence time, 8 h operation).

Synthesis and catalytic applications of C3-symmetric tris(triazolyl)methanol ligands and derivatives

“…53 The catalytic performance of phenyl-and 3,5-bis(trifluoromethyl)phenylsubstituted diarylprolinol derivatives 23a and 23c, respectively, was compared in the enantioselective Michael−Knoevenagel domino 52,53 and were successfully applied in the asymmetric α-amination of linear aldehydes with dibenzyl azodicarboxylate. 55 The optimal system 23f showed very good recyclability under batch conditions and allowed long-standing continuous flow operation.…”

An Integrated Lab‐on‐a‐chip Approach to Study Heterogeneous Enantioselective Catalysts at the Microscale

“…Cat. 2 was utilized for studying the asymmetric α‐amination reaction of aliphatic aldehydes 4–7 with dibenzyl azodicarboxylate (DBAD) 8 in a flow regime (Figure A). In this set of experiments, very low conversions were observed under different flow conditions.…”

Catalytic Enantioselective Flow Processes with Solid‐Supported Chiral Catalysts

“…In flow, however, this technical solution was not possible, so we had to increase the concentration of aldehyde (5‐fold excess) to favour the enamine formation pathway over the addition to the azodicarboxylate. With this premise, the flow experiment was carried out at 0.15 mL min −1 for a total operation time of 8 h, the residence time being as low as 6 min (Figure ).…”